Breast Cancer Research – Treatment Results Quantified

March 4, 2015 by in category cancer research with 0 and 0

fight-breast-cancerBreast Cancer changes everything – your perspectives, your expectations and a lot of women discover the inner resolve and resilience that they never knew they had, to brace up to fight and even beat the cancer.

Welcome to the most detailed page on breast cancer treatments and research. We have accumulated easy to understand treatment results from various clinical trials across the world.

We have over 5 dozen approved breast cancer treatment documented and explained in a simple way and interlaced with over 100 result revealing charts and videos revealing important facets of treatment.

Encouraging Statistics

Let us explore some key facts – some of which we are sure will give you hope.

  • Breast cancer treatment have come a long way. Today, more women are surviving this disease than ever before.
  • More than 80% of women survive 5 years or more compared to 50% 4 decades back. When the cancer is detected early, the 5 year survival and cure rate is much higher – more than 90%.
  • Unfortunately in women whose cancer is detected at a very advanced stage where the cancer has spread to vital organs – the 5 year survival statistic is only 15%.
  • In the last decade mortality rates have fallen by 20%. It is expected to further improve in the next 10 years.
  • 75% of women diagnosed with breast cancer survive for 10 years or more. 66% of women survive 20 years or more. In a lot of women who go into remission, the cancer doesnt come back and they live normal healthy lives.

Breast Cancer Clinical Studies

The following data is meant to offer a simple understanding of the various clinical trials and how the patients responded to the various treatments. Most of the clinical studies on this page are of approved medications in use currently although rarely you will find the odd experimental study.

Note: Breast cancer is one of the more treatable cancers unless it is diagnosed at a very advanced stage. The prognosis is encouraging as explained above – however please note that there are quite a few treatment results listed in the following sections where in advanced stage – the survival rate is poor. This is mostly because of 2 reasons and you should know so as to not be unnerved.

Firstly, the poor results depicted are usually when the cancer has gone metastatic – Secondly – the overall survival period, which is often referred to in clinical trial terminology, does not take into account the patients that were lost to followup.

Not just that, the patients that survived the full period of the study are also not taken into account. Only patients who met death are included for the statistic called ‘Overall Survival”. This in our opinion skews the statistic. We just want you to know this upfront. Pl keep this in mind while viewing the studies on advanced breast cancer.

Can Docetaxel (Taxotere) decrease the cancer relapse rate in women with early stage breast cancer undergoing standard chemotherapy treatment post successful surgery? 1

Women suffering from early breast cancer generally undergo chemotherapy after surgery to reduce chances of recurrence (re-occurrence of cancer). A clinical trial was conducted to see if addition of the drug Docetaxel (Taxotere) in such patients (along with on-going chemotherapy) would improve treatment outcome and reduce chances of recurrence in patients.

Before proceeding further you may want to watch the video below that gives an overview of Stage 0 or 1 cancer.

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Early Stage Breast Cancer (Stage 0-1)

This trial was conducted by Dr. Paul Ellis and Professor Peter Barrett-Lee in collaboration with Cancer Research UK, Experimental Cancer Medicine Centre (ECMC), Guy’s and St Thomas’ NHS Foundation Trust, Institute of Cancer Research (ICR), National Institute for Health Research Cancer Research Network (NCRN), Scottish Cancer Research Network, Wales Cancer Trials Breast Group, Yorkshire Breast Cancer Group.

The trial involved 4162 women who were divided into 3 groups.

  • Group 1 was given FEC chemotherapy and Docetaxel
  • Group 2 was given only FEC chemotherapy
  • Group 3 was given only ECMF chemotherapy

FEC chemotherapy and ECMF chemotherapy are standard chemotherapy procedures, commonly used in treatment of breast cancer. They use the following drugs:
FEC -Fluorouracil, Epirubicin and Cyclophosphamide &
ECMF – Epirubicin, Cyclophosphamide, Methotrexate and Fluorouracil respectively.

effectiveness of docetaxel in early stage breast cancer
After 5 years of treatment, there were more women in Group 2 (those who took Docetaxel) who were free from breast cancer. However, this difference was not substantial enough for addition of Docetaxel to be considered effective in stopping breast cancer from recurring in these women. It is also to be noted that women who had Docetaxel had more side effects than the other groups.

In conclusion, supplementing standard chemo regimen with Docetaxel was not found to be decidedly better at stopping early stage breast cancer coming back after surgery.

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Lumpectomy Conserves Breast Tissue

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About Different Breast Cancer Surgeries

Does introducing Epirubicin along with standard chemotherapy treatment in women who have undergone surgery for early stage Breast Cancer improve overall survival rate? 2

Early stage breast cancer is commonly treated by surgery followed with chemotherapy to reduce risk of cancer recurrence (cancer coming back). CMF is a widely used, standard chemotherapy treatment which includes the drugs Cyclophosphamide, Methotrexate and Fluorouracil. This trial aims to find out if addition of a fourth chemotherapy drug called Epirubicin to this treatment regimen (CMF) would bring additional treatment benefit.

For this trial, 2391 women having breast cancer were enrolled and allocated to 2 treatment groups:

  • Group 1 had 1189 participants who were given Epirubicin and CMF both
  • Group 2 had 1202 participants who were given CMF alone

Epirubicin in treating breast cancer

As the graph shows, after 5 years of treatment, more women of Group 1 were alive. Cancer recurrence was also lower in Group 1. Some side effects such as hair loss, feeling of being sick were seem more in Group 1 while other side effects like drop in number of blood cells were almost comparable in both groups.

Trial results suggest that standard chemo(CMF) + Epirubicin is a better adjuvant treatment approach compared to only standard chemo for women who have undergone surgery for early breast cancer.

What works better – Epirubicin or Methotrexate – when used in combination with Cyclophosphamide & Fluorouracil in premenopausal women with Node Positive Breast Cancer 3

Levine and co-researchers from the ‘National Cancer Institute of Canada Clinical Trials Group‘ conducted a clinical trial involving node-positive breast cancer patients to compare the effectiveness of two different treatments in them.

Between 1989 and 1993, 710 pre-menopausal women (women who have not reached menopause) and perimenopausal women (women who are going to experience menopause in near future) with node-positive breast cancer were randomly assigned to either of the 2 treatment groups:

  1. Group 1 patients (351) received: Cyclophosphamide + Epirubicin + Fluorouracil
  2. Group 2 patients (359) received: Cyclophosphamide + Methotrexate + Fluorouracil

The participants of the trial were followed up for 10 years.

Methotrexate vs Epirubicin in treating breast cancer

More Group 1 patients survived (overall as well as relapse free) than Group 2 patients at the end of 10 years after initiation of treatment. Unacceptable/toxic side effects of treatment were very marginal in both treatment groups.

Treatment with Cyclophosphamide, Epirubicin and Fluorouracil appears to be more effective than Cyclophosphamide, Methotrexate and Fluorouracil in premenopausal as well as postmenopausal women with node-positive breast cancer.

Often doctors use both Epirubicin and Methotrexate to supplement the combination of Cyclophosphamide and Fluorouracil and that seems to get better results for many patients, although each case is different and the doctor finally reaches a good combination.

Comparing 4 different chemotherapy regimens in patients with stage 2, 3 or 4 breast cancer, requiring chemotherapy before surgery 4

Dr. Helena Earl, with support from Bristol-Myers Squibb, Cancer Research UK, Eli Lilly and Company Limited, Experimental Cancer Medicine Centre (ECMC) and National Institute for Health Research Cancer Research Network (NCRN) conducted a clinical trial on women suffering from Breast Cancer.

Often, in breast cancer patients, when the tumor size is large, patients are given chemotherapy to shrink the size of the tumor which is then operated upon. This type of treatment is known as neo-adjuvant therapy.

Before proceeding further, please have a look at the following video that explains tumor grades.

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About Tumors


This trial was conducted to find out the best combination of chemotherapy drugs and the order in which they should be given to these women who need to be given chemotherapy before surgery.

Commonly used chemotherapy drugs include Epirubicin, Cyclophosphamide and Paclitaxel. In this trial, researchers used another chemotherapy drug called Gemcitabine in addition to these above mentioned drugs and administered dosage in different order. This was done to find out if Gemcitabine was beneficial if given to these patients and to know the optimum order of giving these drugs which would be most beneficial in reducing the tumor. All these drugs have been approved by the FDA (Food and Drug Administration) to be used for treatment of breast cancer.

831 women with stage 2, 3 or 4 breast cancer were enrolled in the study and divided randomly into 4 groups. Each group was given a different combination and/or order of drugs:

  • Group 1: Epirubicin and Cyclophosphamide first and then Paclitaxel
  • Group 2: Paclitaxel first and then Epirubicin and Cyclophosphamide
  • Group 3: Epirubicin and Cyclophosphamide first and then Paclitaxel and Gemcitabine
  • Group 4: Paclitaxel and Gemcitabine first and then Epirubicin and Cyclophosphamide

Chemo response involving the drugs - Epirubicin, Cyclophosphamide, Paclitaxel, Epirubicin and Gemcitabine in breast cancer patients undergoing adjuvant therapy

Tumor lesions disappeared entirely (complete response) in more women of Group 2 and Group 4 (20%) compared to Group 1 and Group 3 (15%).

However when these women were followed up for upto 4 years, it was found that survival rates and remission period were good but similar for all the groups.

Giving Paclitaxel at the beginning of chemotherapy seems helpful in improving treatment response among these women but doesn’t seem to make noticeable difference in their overall remission period or survival time.

However, the initial better response achieved by introducing Paclitaxel first is useful as it eases the complication of the adjuvant therapy (when and if this chemo regiment is followed by surgery if needed).

Is Capecitabine a good alternative to standard chemotherapy in older women with stage 1 to 3 breast cancer who have already undergone surgery? 5

The National Cancer Institute (NCI), Eastern Cooperative Oncology Group, Southwest Oncology Group, NCIC Clinical Trials Group and the Cancer and Leukemia Group B conducted a clinical trial in 2012 to compare the effectiveness of Cyclophosphamide versus Capecitabine in treatment of older women who have undergone surgery for breast cancer.

633 breast cancer patients who had undergone surgery for the same were enrolled in the clinical trial. They were then randomly divided into 2 treatment groups:

  • Group1 included 326 patients who were given standard chemotherapy (Cyclophosphamide + Methotrexate + Fluorouracil OR Cyclophosphamide + Doxorubicin)
  • Group 2 included 307 patients who were given Capecitabine

Capecitabine for breast cancer

Standard chemotherapy group survived longer with fewer cases of relapse within 2.4 years of treatment. Considerably more women of Group1 (standard chemotherapy) were living without recurrence of cancer after 2.4 years (ref: Graph).

Standard Chemotherapy using Cyclophosphamide + Methotrexate + Fluorouracil and Cyclophosphamide + Doxorubicin seems to be more efficient in improving prognosis and enhancing relapse free longevity as well as overall survival in older women suffering from breast cancer who have had a surgery.

Capecitabine does not seem to be a better alternative to the standard chemo agents, but even so, it is a powerful anti metabolite with proven ability to inhibit cell growth and dna repair and is often used by doctors in conjunction with other standard chemotherapy drugs, especially in invasive breast cancer.

Before proceeding to further treatment outcomes, lets have a quick overview of stage 2 and stage 3 cancers.

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Stage 2A and 2B Breast Cancer

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Stage 3A, 3B & 3C Breast Cancer

Comparing 2 different treatments – (Epirubicin + Cyclophosphamide + Paclitaxel) Vs (Epirubicin + Cyclophosphamide + Paclitaxel + Gemcitabine) in women with early stage Breast Cancer 6

A clinical research study conducted by Dr. Chris Poole with support from the Cancer Research UK, Experimental Cancer Medicine Centre (ECMC), National Institute for Health and Research Cancer Research Network (NCRN) compared the effect of two different treatment regimens women with early stage breast cancer.

Often, early stage breast cancer is treated with surgery which is followed by chemotherapy to prevent it from coming back. The drugs Epirubicin, Cyclophosphamide and Paclitaxel are commonly used for chemotherapy in such patients. This trial explored the effects, if any, caused by the addition of another drug called Gemcitabine to the treatment regimen of these patients.

3152 women with early stage breast cancer were enrolled in the trial and were divided into two equal groups.

  • Group 1 was given Epirubicin + Cyclophosphamide + Paclitaxel
  • Group 1 was given Epirubicin + Cyclophosphamide + Paclitaxel + Gemcitabine

The effect of this trial was evaluated in terms of reduction in cancer recurrence (coming back), tolerability of the treatment and side effects caused due to it in participants of both groups after a 3 year follow up period.

The remission period was about the same in both groups. This suggests that there is no added potency in the treatment given to Group 2 (Epirubicin + Cyclophosphamide + Paclitaxel + Gemcitabine).

Over 600 women answered quality of life questionnaires. It came to light that the women who had all 4 drugs (i.e. Group 2 participants) reported more side effects, such as sickness, tiredness, diarrhea and sore mouth. But the difference between the 2 groups was not of much significance.

How effective is Trastuzumab and Anastrozole in treating advanced breast cancer 7

Dr. Alison Jones conducted a research, with support from F. Hoffmann La Roche Ltd and Genentech Ltd on postmenopausal women having secondary breast cancer (cancer which has spread to other parts of the body) to compare if using the drug Anastrozole in combination with Trastuzumab was more effective in treating these women compared to Anastrozole alone.

Anastrozole is a hormone therapy used for women who have breast cancer and have already gone through menopause (postmenopausal). Trastuzumab is a biological therapy which kills breast cancer cells that make too much of a protein called HER2 which further aids cancer increase and spread. Trastuzumab is thus used in breast cancer patients who are HER2 positive (i.e. those patients who produce too much of HER2).

This study was conducted with an aim of finding out if the combination of these 2 drugs was better than Anastrozole alone in treatment of postmenopausal, HER2 positive women suffering from secondary breast cancer.

Hence, 208 postmenopausal, HER2 positive, secondary breast cancer women were enrolled in the study and divided equally into 2 treatment groups:

  • Group 1 had 104 patients who were given only Anastrozole
  • Group 2 had 104 patients who were given Anastrozole + Trastuzumab

Complete response statistic with Anastrozol and Trastuzumab when used in breast cancer patients

Cancer Response (i.e. reduction or complete disappearance of tumor after treatment) given by patients in both groups was as follows:

  • Less than 7% participants of Group 1 (Anastrozole) and
  • More than 20% participants of Group 2 (Anastrozole + Trastuzumab) gave good response to treatment

breast cancer relapse time when treated with Anastrozol- andTrastuzumab

Graph above shows that Group 2 participants were able to remain cancer-free for a longer time than Group 1. Cancer started re-growing within 2.5 months of treatment in Group 2 participants while it took 5 months in Group 1 participants. Secondary breast cancer is more difficult to treat and it unfortunately shows in the above statistic.

Although a very small number of women had serious side effects after treatment, some participants in both group chose to stop treatment owing to side effects.

side effects statistic when Anastrozol and Trastuzumab were used to treat breast cancer

More women in Group 2 opted out of treatment due to unmanageable side effects than Group 1

The combination of Trastuzumab and Anastrozole is much more effective than Anastrozole alone for improving prognosis in postmenopausal, HER2 positive women with secondary breast cancer.

How effective is the Combination of Epirubicin, Docetaxel, Cyclophosphamide and Trastuzumab as Neoadjuvant Therapy in Stage 2 & 3 Breast Cancer Patients? 8

Early breast cancer is commonly treated by surgery followed by chemotherapy to prevent recurrence (coming back) of cancer. However, in some cases, the tumor is so large that it cannot be easily removed by surgery. Here, doctors give chemotherapy before operating to reduce the tumor size and thereafter do the surgery. This type of chemotherapy which is given before surgery is known as neo-adjuvant therapy.

Accelerated Community Oncology Research Network and Aventis Pharmaceuticals did a clinical research trial in 2012 to find out the effectiveness of using 4 anti-cancer drugs: Epirubicin, Docetaxel, Cyclophosphamide and Trastuzumab as neoadjuvant therapy in women suffering from Stage 2 & 3 breast cancer. The trial also aimed to see how well the patients were able to tolerate the therapy and study the side effects experienced by them.

30 women with stage 2 or 3 breast cancer were enrolled in the study and given neoadjuvant therapy using above mentioned 4 anti-cancer drugs.

breast cancer treatment response to the combinations of the drugs - Epirubicin, Docetaxel, Cyclophosphamide and Trastuzumab
The women in the trial gave very good response to treatment. The cancer disappeared completely in 71.4% of them while there was appreciable reduction in cancer among 18.5%. The disease remained stable in rest of the women (7.4%)

stats showing side effects when breast cancer patients were treated with the drugs - Epirubicin, Docetaxel, Cyclophosphamide & Trastuzumab
The researchers wanted to find out how well the treatment as tolerated by the participants to know the feasibility of the treatment in such patients. For this, they found out how many women were able to complete at least 85% of the planned dose on schedule.

They also found out how many participants faced serious side effects of treatment. While most of the women (60%) were able to complete the dose on time, some of them (13.3%) reported serious side effects.

The combination neo-adjuvant therapy with the drugs – Epirubicin, Docetaxel, Cyclophosphamide and Trastuzumab – was well tolerated and was effective in bringing good treatment response to the trial participants.

Anastrozole Vs Tamoxifen – Which is better at treating early stage Breast Cancer 9

Certain breast cancers are hormone receptor positive which means that they are encouraged to grow by hormones (oestrogen and progesterone). In order to counter the action of these hormones, hormone therapy is commonly used by doctors for hormone receptor positive breast cancer.

At the time when this trial was started, Tamoxifen was a standard hormone therapy drug, with proven effectiveness in women who had surgery for early breast cancer. This trial was conducted to compare the effectiveness of the standard drug Tamoxifen with another type of hormone therapy drug called Anastrozole and also compare it with a combination treatment which used both Tamoxifen and Anastrozole.

This trial was undertaken by Prof J Cuzick and David Cameron in collaboration with AstraZeneca, Cancer Research UK, Experimental Cancer Medicine Centre (ECMC) and the University of Edinburgh.

For this, a total of 9366 women who had already experienced menopause (postmenopausal women) and had undergone surgery for breast cancer were enrolled and divided into 2 treatment groups. Women who had hormone receptor positive breast cancer as well as those who had other type of breast cancer were enrolled in the study.

  • Group 1 had 3125 participants who were given only Anastrozole
  • Group 2 had 3116 participants who were given only Tamoxifen
  • Group 3 had 3,125 participants who were taking Tamoxifen and Anastrozole

The research team quickly realized that Group 2 and Group 3 were giving similar treatment response and so were randomly put on a course of either Anastrozole or Tamoxifen.

5216 out of the 9,366 women responded to the treatments very well. Upon further testing, it was found that the women who had hormone receptor positive breast cancer responded better to treatment compared to other women.

The graph below shows the number of hormone receptor positive women in whom cancer had come back, 10 years after treatment.

Breast cancer relapse rate in patients treated with Anastrozole and Tamoxifen

The treatment response in general with both the drugs are encouraging. But more women who were given Anastrozole gave ‘good treatment response’ compared to those given Tamoxifen. After 10 years of treatment, cancer came back in more women of Group 2 (Tamoxifen) compared to Group 1 (Anastrozole).

Not just that, it was found that women taking Anastrozole developed lesser side effects and less likelihood of developing secondary cancers or cancer on the other breast.

Results suggest that Anastrozole is better than Tamoxifen in improving treatme[wpsr_socialbts]nt response as well as in preventing cancer from coming back in women suffering from hormone receptor positive early breast cancer.

Before proceeding further, have a look at the video below that explains breast cancer receptors and how they affect the cancer.

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About Breast Cancer Receptors

Effectiveness of Capecitabine and Cyclophosphamide when used in combination to treat Stage 4 Metastatic ER+ Breast Cancer 10

Cyclophosphamide and Capecitabine are both commonly used, effective anti-cancer drugs used in chemotherapy treatment of breast cancer. They both work in different ways to prevent growth and spread of cancer cells. Researchers therefore believed that using both these drugs together might be more effective than using each drug alone.

This trial was planned with the aim of studying the effect of using both these chemotherapy drugs in treatment of women with Stage 4 Metastatic disease (M1) breast cancer. Southwest Oncology Group and the National Cancer Institute (NCI) carried out this clinical trial in 2013.

All patients in this clinical trial were in an advanced cancer stage where the cancer had metastasized to other areas. It is a critical stage with a bleak prognosis. These women had cancers that were Estrogen positive, so they might respond to targeted therapies.

In all 96 women with stage 4 breast cancer were enrolled in the study. But only 40 completed the study either till death or until completion of study(2 years).

Treatment response in metastasized stage 4 breast cancer patients with positive ER receptor

Considering the critical stage of the metastasized advanced stage breast cancer, a considerable proportion of the women showed either complete or partial response to treatment. More than 1/3 got encouraging results.

Treatment response in metastasized stage 4 breast cancer patients with positive ER receptor

The median progression free survival for these women was 5.9 months which means atleast half of these women lived without any increase in their disease was at least 5. 9 months. The highest duration for which a woman of this study lived without worsening of disease was 8.0 months while the lowest was 3.7 months.

With or without increase in disease, atleast 50% of these women lived for minimum of 18.8 months. Longest time of overall survival (i.e. living with or without disease progression) was 22 months while the shortest was 13 months. Very few women showed serious side effects of treatment.

The prognosis might look bleak – but remember that overall survival stats shown above are entered for only those women who died – this means that if any patient in the initial batch of 96 were lost to followup or even survived more than the duration of the study – they were excluded. No reason why you cant outlive the statistic portrayed in this clinical trial.

The combined effect of 2 powerful chemotherapy drug: Cyclophosphamide and Capecitabine brought encouraging prognosis in women with stage 4 breast cancer with metastasis(M1).

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Metastatic/Stage 4 Breast Cancer

Effectiveness of different hormone therapies in treating post-menopausal women having hormone sensitive Breast Cancer which continued to grow after initial hormone therapy. 11

Certain breast cancers are hormone sensitive which means that they are encouraged to grow by hormones (oestrogen and progesterone). In order to counter the action of these hormones, hormone therapy is commonly used by doctors for hormone sensitive breast cancer. Anastrozole is a hormone therapy drug which reduces the amount of oestrogen produced in the body, thereby prohibiting cancer cell growth.

However, with passage of time, treatment with Anastrozole may cause the breast cancer cells to become used to low levels of oestrogen, in which case, Anastrozole loses its effectiveness. This would lead to further growth in the cancer cells and thus, progression (worsening) of cancer. In such a case of relapsed treatment resistant advanced breast cancer, further course of treatment poses a dilemma to the doctors – indeed, it becomes difficult to treat.

In order to come up with a solution for this, researchers conducted a trial where they tested three different hormone therapy combinations against each other to see which the most effective one was. This trial was done by Prof Stephen Johnston in association with AstraZeneca, Cancer Research UK, Institute of Cancer Research (ICR), National Institute for Health Research Cancer Research Network (NCRN) and The Royal Marsden NHS Foundation Trust.

723 postmenopausal women suffering from hormone sensitive breast cancer which continued to grow even after being treated with Anastrozole were enrolled in the trial and divided into 3 equal treatment groups, each containing 241 participants.

  • Group 1 was given Fulvestrant + Anastrozole
  • Group 2 was given Fulvestrant and a Placebo (dummy drug is given to patients but they are unaware of this and think that they are being given the actual drug).
  • Group 3 was given Exemestane

Exemestane is a hormone therapy drug similar to Anastrozole while Fulvestrant belongs to a different group of hormone therapy drugs.

Exemestane-Fulvestrant-treatment-result

As can be seen in the graph above, the average duration of Progression Free Survival i.e. duration for which a patient lives without any further spread of cancer was more or less similar for all 3 groups. Overall was alike for women in all 3 treatment groups. If the cancer in the women had not developed resistance to hormonal treatments, you would see a different scenario were the prognosis would be excellent.

Women in all groups experienced some side effects like joint pain, tiredness, hot flushes and feeling of being sick. However, these were mild and manageable.

In the absence of any considerable difference in the survival durations of all 3 groups, it can be concluded that all 3 treatments used here give similar results and the introduction of Exemestane didn’t produce noticeable improvement in prognosis in women who were developing resistance to hormone treatments like Anasrozole.

Is Anastrozole More Effective than Letrozole in Treating Hormone Sensitive Breast Cancer? 12

The female hormones oestrogen and progesterone may encourage breast cancer cells to grow. Such type of breast cancer which is sensitive to hormones (i.e. growth of cancer cells is encouraged by presence of hormones) is called hormone sensitive breast cancer.

Hormone therapy is used in such cases to reduce production of hormones which in turn would help control the cancer. Anastrozole and Letrozole are commonly used hormone therapy drugs. These drugs are often given to breast cancer patients who have already gone through menopause.

This trial was conducted by Professor JM Dixon, Supported by Experimental Cancer Medicine Centre (ECMC) and Novartis to compare the effects of these two drugs on growth of cancer cells of women suffering from breast cancer.

The women enrolled in this trial were administered either Anastrozole or Letrozole 2 weeks before their planned breast cancer surgery. The researchers studied the breast tissue which was taken from the women when they were diagnosed with breast cancer (i.e. breast tissue removed during biopsy).

The video below gives a brief overview of how the cancer is evaluated using the breast tissue.

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Cancer evaluation after biopsy or lumpectomy

This was later compared with the tissue removed by doctors during the surgery. The effect of the drugs on healthy breast tissue and the cancer cells was studied and results were then compared to know effect of each drug.

The trial involved 209 women who were divided into 2 treatment groups.

  • Group 1 had 103 women who were given Anastrozole.
  • Group 2 had 106 women who were given Letrozole.

After surgery, the researchers looked at the levels of biomarkers in the tissue samples of the women. Biomarkers are substances that doctors can measure in the body to help them tell how a disease is developing or how a treatment is working. There was not much difference in the effect of both drugs as indicated by the biomarkers.

Effect of the drugs on breast cancer cells with oestrogen receptors (whose cancer cells are encouraged to grow by oestrogen) as well as those with progesterone receptors (whose cancer cells are encouraged to grow by progesterone) was also studied.

While both drugs worked very well in stopping growth of cancer cells which had oestrogen receptors, they didn’t work very well on cancer cells that had progesterone receptors.

Both Anastrozole and Letrozole seem to be equally effective in treating hormone sensitive breast cancer and provide encouraging prognosis. Doctors often combine this with surgery and completely eradicate the cancer.

Combined effect of Capecitabine and Fulvestrant in post-menopausal women with Hormone Receptor Positive Metastatic Breast Cancer 13

The type of breast cancer which has spread to other parts of the body is known as Metastatic breast cancer and are hard to treat because they have advanced and are often more treatment resistant. But if the cancer is hormone receptor positive (oestrogen and progesterone), the cancer can still be arrested.

Accelerated Community Oncology Research Network, Hoffmann-La Roche and AstraZeneca conducted a clinical trial in 2012, on women with hormone receptor positive metastatic breast cancer to see if combination of two FDA (Food and Drug Administration) approved anti-cancer drugs: Capecitabine and Fulvestrant was helpful in improving prognosis in these women.

This trial involved 41 postmenopausal women with hormone receptor positive metastatic breast cancer. These women were given Capecitabine as well as Fulvestrant and their treatment response, average progression free survival (duration for which patient lives without increase in cancer) as well as average overall survival (duration for which patient lives with or without increase in cancer) was measured.

Treatment response when treating metastatic cancer with Capecitabine and Fulvestrant

Graph above shows that the median duration of progression free survival among these women was 14.9 months. This means that half of the women lived without disease progression for minimum of 14.9 months. The shortest duration for which a woman in this study lived without any increase in her disease was 7.6 months.

Similarly, median duration of Overall Survival (OS) was calculated. Atleast 50% of the women lived for minimum of 28.6 months. The smallest duration of OS was 23.95 months. There were many women who were not available to confirm prognosis, so it is entirely possible that some women may have had better responses than what was available to be measured.

Treatment response when treating metastatic cancer with Capecitabine and Fulvestrant

Most of the women showed no change in their disease (68.3%). Nearly 20% showed considerable reduction in cancer i.e. partial reduction and in about 5% of them, cancer disappeared completely. However, in some of them (7.3%) cancer had spread further in spite of treatment. Very few women in the trial experienced severe side effects of the treatment.

Prescribing Capecitabine along with Fulvestrant appears to benefit postmenopausal women with hormone receptor positive, metastatic breast cancer.

Can Anastrozole prevent Breast Cancer in post-menopausal women who are deemed high risk? 14

The female hormone Oestrogen may encourage breast cancer cells to grow and thus aid in spreading of breast cancer. Drugs belonging to the group “Aromatase Inhibitors” e.g. Anastrozole are used commonly by doctors to stop production of oestrogen in the body and thus help suppress further spread of breast cancer in those postmenopausal women who already have it.

Doctors thus thought it worthwhile to find out if giving Anastrozole (a commonly used Aromatase Inhibitor drug) to postmenopausal women (women who have already passed through menopause) who are at high risk of developing breast cancer can help in prevention of breast cancer among them.

This research trial was conducted by Professor Jack Cuzick, Professor John Forbes and Professor Anthony Howell in collaboration with AstraZeneca, Cancer Research UK, National Institute for Health Research Cancer Research Network (NCRN), Queen Mary University of London and Sanofi Aventis.

The trial enrolled 3864 postmenopausal women who were at high risk of developing breast cancer in the future due to:

  • Strong family history of breast/ovarian cancer
  • Presence of LCIS (Lobular Carcinoma in Situ)/DCIS (Ductal Carcinoma in Situ). This means that some of the cells in lobules or ducts of breast/s have turned abnormal.
  • Presence of benign breast diseases.
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Risk Factors

The participants of the trial (3864) were randomly allocated to two treatment groups. Neither the participants themselves nor the doctors who were conducting the research were aware which treatment group was receiving which treatment. This type of research study is called a double blind study. This is done so that no bias is present from side of participant or researcher (in this case, the doctors performing the research study).

  • Group 1 had 1920 participants who took Anastrozole every day for 5 years
  • Group 2 had 1944 participants who tool a Placebo (Placebo means – patient is under impression that she is receiving actual drug but is actually being given a dummy drug which does not have the effects of actual drug. This is done to know the psychological effect on health of patients who are taking dummy drug with belief that it is actual drug versus health effects on patients taking actual drug).

At the end of 5 years, researchers found out how many of these women developed breast cancer.

Anastrozol in breast cancer prevention

Twice as many women in placebo group developed breast cancer after 5 years of treatment compared to the women that was given Anastrozole indicating a clear and considerable positive preventive effect of Anastrozole in postmenopausal women at high risk of getting breast cancer. However, presence of side effects such as joint pain, stiffness in joints, hot flushes and dry eyes was higher in women who were given Anastrozole.

The researchers of this trial concluded that Anastrozole has shown the potential to reduce risk of breast cancer in postmenopausal women who are considered high risk of developing breast cancer.

Is addition of AZD8931 to Anastrozole helpful in Treating Postmenopausal Women with Hormone Sensitive Breast Cancer? 15

This trial focused on postmenopausal women (women who had already gone through menopause) who had hormone sensitive breast cancer (type of breast cancer which is encouraged to grow by presence of hormones) which was either limited to the breast or had spread elsewhere in the body.

Doctors commonly use hormone therapy for hormone sensitive breast cancer. An effective hormone therapy drug is Anastrozole. Hormone therapy drugs aid in treatment of breast cancer by stopping the production of the hormones responsible for encouraging the growth of cancer cells.

In this trial, researchers assessed if the addition of a biological therapy drug (AZD8931) to Anastrozole was safe and would improve the prognosis of these women. Biological therapy drugs work by blocking certain proteins present in cancer cells which signal cancer cells to divide and thus increase in number.

This trial was conducted by Professor Stephen Johnston in association with AstraZeneca, Experimental Cancer Medicine Centre (ECMC) and the National Institute for Health Research Cancer Research Network (NCRN).

All the women who were enrolled in the trial (359 women with hormone sensitive breast cancer, previously untreated with any hormone therapy) were randomly divided into 3 treatment groups. Neither the doctors nor the patients themselves were aware which treatment was being given to which group.

This type of research study is called Double Blind Study. This is done in order to avoid bias on part of either researcher or participants and hence ensure accurate results.

  • Group 1 had 118 women who were given Anastrozole + Low Dose of AZD8931 tablets
  • Group 2 had 120 women who were given Anastrozole + Higher Dose of AZD8931 tablets
  • Group 3 had 121 women who were given Anastrozole + Placebo (Placebo means – patient is under impression that she is receiving actual drug but is actually being given a dummy drug which does not have the effects of actual drug. This is done to know the psychological effect on health of patients who are taking dummy drug with belief that it is actual drug versus health effects on patients taking actual drug).

Effect of introducing AZD8931to Anastrozole

 

Results presented in the above graph suggest that there was no beneficial effect of the additional biological therapy drug. Additionally, serious side effects were more common in the groups that were given this drug (Group 1 & 2) compared to the group receiving only Anastrozole (Group 3). Due to this, many women of Group 1 & 2 dropped out of the study.

These results prompted the data monitoring committee to recommend the termination of this trial because, looking at the results, it was clear that the trial would not be able to show any positive effects of adding the biological therapy drug (AZD8931) in any dosage, to Anastrozole for treating postmenopausal women with hormone sensitive breast cancer.

How effective is Giving Goserelin in addition to Letrozole on Women Younger than 35 years who have Advanced Breast Cancer? 16

Although it is rare, when breast cancer occurs in women younger than 35 years of age, it has poorer prognosis i.e. chances of the person surviving for long are less. In this trial conducted in 2013, Liu and co-researchers wanted to see how effective it is to combine two drugs: Goserelin and Letrozole (anti-cancer drugs approved by the Food and Drug Administration – FDA) as first-line therapy for treatment of these pre-menopausal women suffering from advanced breast cancer. First-line therapy is the first treatment given to the patient after diagnosis.

35 women who were diagnosed with breast cancer when they were younger than 35 years of age were made a part of this study and given Goserelin 3.6 mg injection once every 4 weeks along with Letrozole 2.5 mg daily by mouth.

The treatment response was measured in the patients in terms of

  • Complete Response – disappearance of cancer
  • Partial Response – significant reduction in cancer
  • Stable Disease – no change (increase or decrease) in cancer
  • Progressive Disease/Death – increase in cancer or death

Researchers also found out:

  • Progression Free Survival – duration for which the patient survived without any increase in their cancer
  • Overall Survival – duration for which the patient survived.

Treatment response to Goserelin and Letrozole

As shown in the graph above, only few women showed complete disappearance of tumor (2.9%) while many of them had a reduction in their cancer (22.9%) and nearly 40% had stability of disease i.e. no increase or decrease. However, some of them also had increase in disease and/or death (34.3%).

overall survival rate in young women treated with Goserelin and Letrozolefor for advanced breast cancer

Atleast half of the women lived without further spread in cancer for 9.6 months or more. The longest duration for such progression free survival among these women was up to 58 months while shortest was 5 months.

The median duration of Overall Survival (OS) was 33 months. This can be understood in this way; 50% of the women lived for at least 33 months, irrespective of disease progression. The lowest overall survival was 6 months while some women were alive for 72 months. None of the women involved in the trial experienced any serious side effects of treatment.

Combination treatment of Goserelin + Letrozole seems to be well tolerated and effective in these young women with advanced breast cancer.

Comparing the Effectiveness of Exemestane versus Tamoxifen followed by Exemestane in Treatment of Postmenopausal Women Suffering from Hormone Sensitive Early Breast Cancer 17

Early stage, oestrogen sensitive breast cancer (type of breast cancer which is encouraged to grow by presence of hormone – oestrogen) in postmenopausal women is commonly and effectively treated with hormone therapy drugs. Tamoxifen is one such hormone therapy drug which has been proven effective in lowering risk of breast cancer recurrence (coming back) when taken for 5 years.

Other types of hormone therapy are also known to reduce risk of recurrence of breast cancer. Keeping this in mind, in this trial, Dr. Daniel Rea compared two different hormone therapy drugs (Tamoxifen and Exemestane) in treatment of postmenopausal breast cancer patients. The trial was supported by Cancer Research UK, Experimental Cancer Medicine Centre (ECMC), National Institute for Health Research Cancer Research Network (NCRN) and the University of Birmingham.

More than 9000 postmenopausal women suffering from oestrogen sensitive breast cancer who had already undergone surgery and possibly, chemotherapy for early breast cancer were enrolled in the study.

Half of the participants (4500 women) took Exemestane from starting i.e. since initiation of treatment for 5 years while the other half (4500 women) took Tamoxifen initially for 2 or 3 years, followed by Exemestane till 5 years of total treatment were reached.

At the end of 5 years, number of women in both groups who were living without cancer coming back was similar i.e. both treatments were equally effective.

Thus, for postmenopausal women suffering from oestrogen sensitive breast cancer, treatment with only Exemestane is as effective as treatment with Tamoxifen followed by Exemestane. Both have excellent outcomes.

Low dose Vs High dose Capecitabine with Docetaxel in treatment of Advanced Metastatic Breast Cancer 18

Women suffering from breast cancer are commonly treated using a class of drugs known as Anthracyclines. However, in certain cases, this treatment fails to restrict the cancer. In such cases, doctors use other anti-cancer drugs to control the spread of cancer.

Hoffmann-La Roche conducted a clinical trial in 2013 on women who had locally advanced (cancer spread in and around the breast) or metastatic breast cancer (cancer which has spread to other parts of the body) which had grown or returned after treatment with chemotherapy using Anthracycline drugs. Needless to say, such cancers are difficult to treat and offer poor prognosis. The trial aimed to compare the effectiveness and safety of higher dose (1250 mg) of Capecitabine to that of a lower dose (825 mg) of Capecitabine given with Docetaxel in such patients.

470 women with locally advanced or metastatic breast cancer which was treated unsuccessfully with Anthracyclines were enrolled in the study and divided into 2 treatment groups. Neither the researcher nor participants could decide which group they would be put into. This is called Randomization which is done in order to avoid any type of bias from researcher or participants themselves and thus ensure accurate trial results.

  • Group 1 had 235 participants who were given higher dose of Capecitabine + Docetaxel
  • Group 2 had 235 participants who were given lower dose of Capecitabine + Docetaxel

 Combination of Capecitabine and Docetaxel - Low dose vs hgh dose treatment response

Graph above shows the median duration for various parameters. The median duration of response in both groups was the same (6.9 months). This tells us that in both groups, 50% of the women responded to treatment for a minimum of 6.9 months.

In Group 1, some women responded for as long as 8.6 months while the shortest duration of response was 6.1 months. In Group 2, longest and shortest duration of response was 9 months and 5.8 months respectively.

Time to treatment failure indicates the duration after which the treatment stopped being effective. In Group 1, treatment was effective for at least 5.1 months in 50% of the women. The lowest and highest duration till which treatment was effective in this group were 4.2 months and 5.8 months respectively. For Group 2, median duration was 4.6 months, lowest duration was 4.1 months and highest was 5.3 months.

Researchers also found out the duration for which each treatment was able to avoid further spread of disease of death in the women. Half of the women of Group 1 were able to remain free from progression for at least 7.9 months. The longest time for which a woman of this group was able to do so was 8.5 months while least time was 6.9 months.

In Group 2, 50% of the women remained free from progression or death for at least 5.8 months. Shortest and longest duration for this was 4.9 months and 7.1 months respectively.

Median duration of Overall Survival (OS) for Group 1 was 16.4 months which means that half of the women in this group lived, with or without spread of disease for at least 16.4 months. The longest duration of OS in this was 21.8 months while the lowest was 13.6 months. The other group had a lower median duration of OS (15.1 months). The lowest and highest duration of OS were also lower for this group (12.9 months and 17.7 months respectively).

To summarize, the higher dose Capecitabine + Docetaxel treatment given to Group 1 was effective for longer time and cancer spread came later in this group. Overall survival was also longer in this group.

 Combination of Capecitabine and Docetaxel - Low dose vs hgh dose treatment response

More women in the first group responded favorably to treatment (ref: Graph 2). Serious side effects were slightly higher though.

The combination of higher dose Capecitabine (1250 mg) seems more effective than lower dose of Capecitabine (825 mg) when used in combination with Docetaxel to treat women with locally advanced or metastatic breast cancer which was previously unsuccessfully treated with Anthracycline chemotherapy.

Clinical Research Study to Assess the Effectiveness of Xyotax in Women with Breast Cancer That has Spread 19

Professor Hilary Calvert, in collaboration with the Cancer Research UK (Drug Development Office) conducted a clinical research study on women who had breast cancer which had spread. ‘Taxanes’ are a group of drugs usually used in Chemotherapy which is an essential part of cancer treatment.

Paclitaxel is one of the drugs belonging to the group ‘Taxanes’ and is often used in the treatment of breast cancer. Xyotax is a new form of Paclitaxel. This trial was conducted to find out if Xyotax is effective in treatment of breast cancer which has spread. Side effects, if any, caused by this drug were also observed as part of the clinical research study.

26 participants (women with breast cancer which had spread) were enrolled in the study. Out of these, 18 participants had taxanes before while 8 were never treated with taxane group of drugs.

Only 4 of the 26 patients showed reduction in cancer and it came to light that Xyotax is most effective in patients previously untreated with any drug belonging to taxane(Paclitaxel) group. However the side effects were pretty severe with some patients suffering nerve damage. Hence, this trial was stopped.

Xyotax is not a good treatment option for breast cancer.

Is Lapatinib + Capecitabine an effective combination in treating HER2 +ve Breast Cancer that is locally advanced or has spread to other parts of the body? 20

Breast cancer cells have many growth factor receptors which, when triggered, cause these cells to divide and increase in number. It is believed that Lapatinib blocks the activity of 2 of such receptors and thus can help in controlling the growth and spread of breast cancer. One of these receptors is HER2 and those patients who have breast cancer which produces excess of HER2 are called HER2 positive breast cancer.

With this in mind, a clinical research trial was conducted to check the effectiveness of the drugs Lapatinib and Capecitabine (commonly used, powerful anticancer drug) used together in treatment of HER2 positive breast cancer which is locally advanced or had spread to other parts of the body. The research trial also aimed to assess the side effects caused due to this treatment. This trial was conducted by Professor D Miles with support from Experimental Cancer Medicine Centre (ECMC) and GlaxoSmithKline (GSK).

The patients enrolled in this trial had HER2 positive breast cancer which produced a lot of growth receptor and their cancer continued to grow despite treatment with commonly used effective chemotherapy drugs such as Herceptin, Epirubicin, Doxorubicin, Paclitaxel and Docetaxel. A total of 4200 people from around the world were included in the trial. All these participants had breast cancer which continued to grow despite best available treatment with medically proven drugs (as mentioned above).

The treatment (Lapatinib + Capecitabine) was able to control cancer growth in more than 50% of the participants. The most common time when cancer started re-growing in patients was 5 months. Participants who had previously never been treated with Capecitabine performed better than those who had it as part of previous treatment. Diarrhea and feeling of sickness were the commonly observed side effects among patients. However, no severe side effects were seen in majority of them.

In conclusion, Lapatinib and Capecitabine drug combination seems safe and effective in treating patients with HER2 positive breast cancer which is locally advanced or spread to other body parts.

Comparing the treatments: Fluorouracil + Epirubicin + Cyclophosphamide (FEC) regimen and Intravenous (IV) Cyclophosphamide + Methotrexate + Fluorouracil (CMF) in patients suffering from Metastatic Breast Cancer. 21

Ackland and co-researchers conducted a clinical trial in 2001 to determine the relative efficacy of a cyclophosphamide epirubicin and fluorouracil (CEF) regimen compared with an intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in metastatic breast cancer.

A total of 460 patients were enrolled in the study and randomly allocated to 2 different treatment groups:

  • Group 1 patients (223) received: Cyclophosphamide + Epirubicin + Fluorouracil
  • Group 2 patients (237) received: Cyclophosphamide + Methotrexate + Fluorouracil

Cyclophosphamide-Epirubicin-Fluorouracil-Methotrexate

More women in Group 1 responded well to treatment compared to Group 2.

 

Efficacy of Fluorouracil + Epirubicin + Cyclophosphamide (FEC) regimen and Intravenous (IV) Cyclophosphamide + Methotrexate + Fluorouracil (CMF)

Half of the women in Group 1 remained free from tumor progression i.e. growth or spread in tumor for at least 8.9 months. This duration was lower in Group 2 (6.3 months). Treatment was effective for a longer time and longevity was also higher in women of Group 1.

While treatment continued to be effective for at least 6.2 months in half of Group 1 women, it was only 5 months in Group 2. Also, 50% of Group 1 women lived for minimum of 20.1 months, with or without increase in disease. This duration was lower (18.2 months) in Group 2.

Since rate & duration of treatment response as well as life span was better in the women receiving treatment regimen of Cyclophosphamide + Epirubicin + Fluorouracil, it emerges as the more powerful therapy for women suffering from metastatic breast cancer.

Is Taxoprexin (Paclitaxel) Beneficial when used in Treatment of Women Suffering from Advanced Breast Cancer? 22

With support from Theradex, Prof Stephen Johnston conducted a clinical trial on women with advanced breast cancer to see the effect of a new drug called Taxoprexin which contains Paclitaxel – an FDA approved taxane (a class of drugs) chemotherapy drug and a fatty acid called DHA.

Fatty acids in the body are consumer by cancer cells, and this includes DHA. So the researchers hoped to use the fatty acid as a Trojan-horse to get paclitaxel into the core of the cancer cells and kill them. This trial was thus conducted with an aim of assessing the effectiveness of this new drug on advanced breast cancer and to know about the side effects caused due to it.

taxoprexin treatment results

As shown in the graph above, majority of the subjects gave either partial response i.e. reduction in tumor or stable disease i.e. no worsening or improvement in tumor (18.4% + 34.2%) while in nearly 45% of the participants, the cancer continued to grow.

Some side effects were noticed – Blood cells count dropped that caused an increased risk of infection apart from bruising and bleeding issues.

The researchers concluded that the new drug Taxoprexin worked no better than the other taxane drugs in women with advanced breast cancer.

Fulvestrant 250 mg vs Fulvestrant 500 mg – Which is better to treat Oestrogen Receptor +ve Breast Cancer in Postmenopausal Women with relapsed or hormone treatment resistant Breast Cancer 23

A type of breast cancer which is sensitive to the female hormone Oestrogen is known as Oestrogen Receptor Positive Breast Cancer. For treatment of this type of cancer, doctors commonly use hormone therapy.

AstraZeneca conducted a clinical trial in 2012 which involved postmenopausal women who had oestrogen receptor positive breast cancer and their cancer had progressed or returned even after being treated with hormone therapy – difficult to treat.

The aim of this trial was to evaluate the efficacy of a new dose of 500 mg Fulvestrant (experimental dose) with the standard dose of 250 mg (currently used by doctors for breast cancer treatment) in these women. The researchers in this trial also wanted to see if the experimental dose was as well tolerated as the standard dose i.e. were there any serious side effects of the experimental dose which would make it difficult or impossible for patient s to take it.

At the beginning of the trial, 736 women with the above mentioned conditions were enrolled. They were then randomly divided into two treatment groups. Neither the researcher nor participants could decide which group they would be put into. Additionally, none of them were aware which group was being given which dose. This is called Randomized, Double Blind Study which helps in removing any bias by participants or researchers and thus gives correct and dependable results.

  • Group 1 had 374 participants who were given standard dose (Fulvestrant 250 mg)
  • Group 2 had 362 participants who were given experimental dose (Fulvestrant 500 mg)

The researchers looked at how well the participants in both groups responded to the different treatments. Following aspects were observed:

  • Overall Response Rate – how many participants showed reduction/disappearance of cancer on treatment
  • Clinical Benefit – how many participants’ cancer remained same, reduced or disappeared after treatment
  • Time to Tumor Progression – time taken by participants’ tumor to start growing after treatment
  • Overall Survival – duration for which participants survived after treatment, with or without increase in their cancer.

Fulvestrant 250mg vs Fulvestrant 500mg

More women who were given the experimental higher dose of Fulvestrant showed improvement in their cancer i.e. clinical benefit

 

Fulvestrant 250mg vs Fulvestrant 500mg

The median duration of response for Group 1 was 16.4 months while it was higher in Group 2 (19.4 months). This implies that half of the Group 1 women responded to treatment for at least 16.4 months. The shortest duration of response for this group was found to be 3.7 months. In Group 2, 50% of the women responded for at least 19.4 months and shortest duration was 5.7 months.

Clinical benefit was experienced by half the women in Group 1 for 13.9 months or more with the lowest duration of clinical benefit being 3.7 months. In Group 2, half the women got clinical benefit for minimum of 16.6 months with shortest duration being 2.5 months.

In Group 1, half of the patients could remain free from disease progression (i.e. increase in disease) for 5.5 months or more while in Group 2 this duration was higher (6.5 months).

With regards to overall survival (OS) i.e. survival with or without increase in disease, the median duration of OS in group 1 was lower than Group 2 (22.8 months v/s 25.1 months).

Serious side effects of treatment were seen in very few participants of both groups. All in all, Group 2 showed better response rate, longer duration of response, clinical benefit and survival compared to Group 1.

The higher dose of Fulvestrant (500 mg) seems more effective than the standard dose (250 mg) in improving prognosis in these women.

Comparing the Effectiveness of Capecitabine + Lapatinib versus Capecitabine alone in Treating Women with Advanced Breast Cancer 24

Breast cancer is commonly treated with surgery, followed by one or more of these treatments: chemotherapy, radiation, hormone therapy and biological therapy. However, these treatments are not effective 100% of the time. Sometimes, the cancer may return or spread elsewhere in the body and is termed Advanced/Secondary/Metastatic cancer and are resistant and difficult to treat with a poor prognosis.

This trial assesses the effectiveness of using a commonly used effective chemotherapy drug (Capecitabine) alone versus in combination with a new drug called Lapatinib. There are many growth factor receptors on breast cancer cells which are responsible for growth and division of cancer cells. Lapatinib works by blocking 2 of these receptors, thus limiting the cancer as well as preventing further spread.

This trial was conducted by Professor Rob Coleman with the support of Cancer Research UK, GlaxoSmithKline (GSK) and the National Institute for Health Research Cancer Research Network (NCRN) on nearly 400 women with advanced breast cancer.

These women were randomly and equally divided into two treatment groups.

  • Group 1 was given Lapatinib + Capecitabine
  • Group 2 was given only Capecitabine

Lapatinib and Capecitabine to treat advanced breast cancer

Graph above clearly shows that more women who were given both drugs (Capecitabine + Lapatinib) gave a good treatment response compared to those given only Capecitabine. This was true for complete response (disappearance of cancer) as well as partial response (reduction in cancer).

time to cancer progression under Lapatinib and Capecitabine treatment

Cancer started re-growing earlier in women who were given only Capecitabine. By comparison, this duration was longer in women taking both drugs (ref: Graph above).

While side effects were experiences by majority of the women in both treatment groups, they happened more frequently in women who were taking both drugs. Common side effects that were experienced included diarrhea, sickness and rash.

In conclusion, the combination of Capecitabine and Lapatinib appears to be more beneficial than Capecitabine alone in treatment of women with advanced breast cancer.

Can Pyridoxine (Vitamin B6) Help Relieve Hand Foot Syndrome Caused by Capecitabine in Breast Cancer Patients? 25

Capecitabine is a commonly used, effective chemotherapy drug routinely used by doctors for treatment of breast cancer. One of its possible side effects is Hand Foot Syndrome (HFS) which causes numbness, tingling, redness or soreness on the palms of hands or feet soles. In most cases it is mild and is not a cause of concern. However, it can be severe in some patients, causing blistering and peeling of skin. This in turn would affect the patient’s quality of life. A more serious consequence of this would be a reduction in dose of Capecitabine to reduce the side effects.

In such a case, doctors often prescribe Pyridoxine (Vitamin B6) which is believed to relieve the symptoms. This trial was conducted by Dr. Pippa Corrie in collaboration with Addenbrookes NHS Trust and the National Institute for Health Research Cancer Research Network (NCRN) to gather scientific evidence in support of this belief.

For this, the trial 106 breast cancer patients were enrolled and randomly divided into 2 groups of 53 participants each.

  • Group 1 participants were given Pyridoxine
  • Group 2 participants were given a Placebo. Neither the researcher nor the patients themselves were aware if they were being given real drug or placebo. This is done to ensure absence of bias in the research study.

Pyridoxine reduces side effects of Capecitabine

More participants who were given Pyridoxine than those given Placebo did not require a dose reduction i.e. could continue with their ongoing dosage treatment of Capecitabine. Presence of Hand Foot Syndrome, particularly, worst cases of HFS was seen in higher number of Placebo group participants.

In conclusion, Pyridoxine has the potential to successfully reduce incidence if hand foot syndrome among breast cancer patients suffering from it as a side effect of the chemotherapy drug Capecitabine.

Doxorubicin in combination with Fluorouracil and Cyclophosphamide Vs Methotrexate in combination with Fluorouracil and Cyclophosphamide (CMF regimen) as adjuvant chemotherapy for operable Breast Cancer 26

Martin and co-researchers from the GEICAM Group (Spanish Breast Cancer Research Group), Spain conducted a clinical trial in 2003 to determine the relative effectiveness of two different treatment methods as additional treatment in patients undergoing curative surgery for breast cancer.

The patients enrolled in the study (985 women undergoing curative surgery for breast cancer) were randomly divided into two groups where:

  • Group 1 received CAF regimen (Doxorubicin + Fluorouracil + Cyclophosphamide)
  • Group 2 received CMF regimen (Methotrexate + Fluorouracil + Cyclophosphamide)

Among those patients who had node negative breast cancer, Disease Free Survival and Overall Survival was much higher in Group 1 (CAF regimen) compared to Group 2 (CMF regimen). Among node-positive breast cancer patients, this difference was not very pronounced.

Risk of recurrence of disease and death was considerably lower in Group 1 (CAF regimen) compared to Group 2 (CMF regimen).

Mild toxicity alopecia (loss of hair from head, other parts of body), emesis (nausea & vomiting), mucositosis (pain and inflammation of the surface of the mucous membrane) and cardiotoxicity (damage to the heart muscle) was seen more in patients of Group 1 (CAF regimen) while more Group 2 (CMF regimen) patients developed conjunctivitis and weight gain as side effects of treatment. However, in spite of the clinical toxicity of FAC being greater than that of CMF, the levels were manageable and clinically acceptable.

In conclusion, CAF regimen efficient than CMF regimen as an additional treatment in women already undergoing curative surgery for breast cancer.

Does introducing Docetaxel to Epirubicin improve prognosis in post menopausal women with Breast Cancer 27

Breast cancer treated with surgery is often followed up with chemotherapy to reduce the risk of recurrence (cancer coming back). Commonly used chemotherapy drugs include Epirubicin and Docetaxel.

This trial conducted by Professor Charles Coombes in collaboration with International Collaborative Cancer Group (ICCG) and the National Institute for Health Research Cancer Research Network (NCRN) aimed to compare the effects of using Epirubicin alone versus Epirubicin in combination with Docetaxel for treating postmenopausal women who had already undergone surgery for breast cancer.

Research shows that starting the drug Tamoxifen during ongoing chemotherapy may increase the patient’s risk of developing a blood clot. The trial also aimed to see if starting the drug Tamoxifen after chemotherapy reduced this risk.

803 postmenopausal women who had undergone surgery for breast cancer were enrolled in the trial. They were then randomly divided into two treatment groups.

  • Group 1 had 397 participants who were given Epirubicin
  • Group 2 had 406 participants who were given Epirubicin + Docetaxel

Epirubicin vs Epirubicin and Docetaxel

Participants who were given both drugs (Group 2) showed better response to treatment compared to those who were given only Epirubicin. Higher percentage of those given both drugs were free from recurrence of cancer after 5 years of treatment and overall, more participants from this group were alive at 5 years compared to Group 1. It should also be noted that side effects were more common among Group 2 participants. However, there was no difference in the quality of life of participants of both groups.

378 women participated in the trial to see effect of Tamoxifen given during or after chemotherapy. Of them half (187) were given Tamoxifen during chemotherapy and the other half were given the drug after completion of their chemotherapy treatment. No difference was found in the number of blood clots in the participants in both treatment groups.

It can be said, based on this trial that Epirubicin coupled with Docetaxel gives good prognosis and is decisively better than prescribing Epirubicin alone in postmenopausal women who have had surgery for breast cancer.

Comparing the effectiveness of giving Ixabepilone every week versus once every 3 weeks to Metastatic Breast Cancer patients 28

Bristol-Myers Squibb collaborated with US Oncology Research in 2012 to carry out a clinical trial which studied the effect of using the anti-cancer drug Ixabepilone in two different doses and frequencies in patients with metastatic breast cancer.

176 women with metastatic breast cancer were included in the trial. They were then divided into 2 treatment groups. Neither the researcher nor participants could decide which group they would be put into. This is called Randomization which is done in order to avoid any type of bias from researcher or participants themselves and thus ensure accurate trial results.

  • Group 1 had 85 women who were given Ixabepilone 16 mg/m2 weekly for 3 weeks followed by 1 week rest.
  • Group 2 had 91 women who were given Ixabepilone 40 mg/m2 every 3 weeks.

Ixabepilone treatment

More women from Group 2 had Progression Free Survival i.e. were alive without any increase in their cancer at the end of 6 months compared to Group 1 women.

Ixabepilone treatment

Women in Group 2 survived longer, with or without aggravation of cancer than women in Group 1.

The median Progression Free Survival (PFS) in Group 1 was 2.9 months which means that half the women in this group lived without worsening of disease for at least 2.9 months. Lowest duration of PFS was 2.7 months and highest was 5.1 months. Group 2 had a higher median duration of PFS (5.3 months) than Group 1. The lowest (3.8 months) and highest (6.2 months) duration of PFs were also higher than Group 1.

Half the women in Group 1 lived 13.9 months or more, irrespective of disease status. Some women in this groups lived for as long as 15.7 months while some could survive up to 12.1 months. In Group 2, median duration of OS was 16.1 months, higher than Group 1. Shortest duration of OS was 10.3 months.

The researchers evaluated the treatment response given by women in both the groups in terms of the following:

  • Complete Response – Disappearance of cancer
  • Partial Response – Reduction in cancer
  • Stable Disease – No increase or decrease in cancer
  • Progressive Disease – Increase in cancer
  • Not Evaluable – Percentage of Women who Withdrew from the Trial due to Side Effects of Treatment / Died

 

Graphs below display the treatment responses of the trial participants in both groups.

Ixabepilone treatment Ixabepilone treatment

Women who were in Group 2 gave much better treatment response than those in Group 1; higher complete response, partial response and stable disease. The cancer worsened (progressive disease) in more women of Group 1 compared to Group 2. The proportion of women who dropped out due to side effects or died was higher in the second group but this difference was not big enough to be considered important.

Few women in both groups had severe side effects due to the treatment given to them. However, these were more commonly seen in women from Group 2 compared to Group 1.

Ixabepilone 40 mg/m2 prescribed every 3 weeks is the better treatment option for metastatic breast cancer.

Is Doxorubicin & Docetaxel combination more effective than Doxorubicin & Cyclophosphamide in women with early, locally advanced or inflammatory Breast Cancer? 29

Professor J Evans conducted a clinical research, in collaboration with the Anglo-Celtic Cooperative Oncology group, on 363 women who required neoadjuvant therapy. They were women who had a tumor that was 3 cm or more in size, or who had locally advanced or inflammatory breast cancer(but early in its spread).

These women were given up to 6 cycles of chemotherapy treatment using either of the 2 treatments:

  • Group 1 patients received Doxorubicin + Cyclophosphamide
  • Group 2 patients received Doxorubicin + Docetaxel

Doxorubicin and Docetaxel vs Doxorubicin and Cyclophosphamide

Women who were given Doxorubicin + Docetaxel showed better treatment response in terms of cancer response, disappearance of cancer signs as well as lower rate of recurrence compared to the women who were given Doxorubicin + Cyclophosphamide.

Doxorubicin + Docetaxel is a better treatment option to Doxorubicin + Cyclophosphamide in early stage breast cancer patients who require neo-adjuvant therapy.

Comparative Study of using Capecitabine alone or in Combination with Trastuzumab (Herceptin) in Women with Advanced Breast Cancer 30

Sometimes, breast cancer cells produce too much of a protein called HER2 which aids growth and spread of cancer cells. This type of cancer is called HER2 positive breast cancer. For treatment of HER2 breast cancer, doctors commonly use a drug called Trastuzumab. However, in some cases the cancer starts to grow again in spite of this treatment and at that time doctors may decide to stop giving Trastuzumab and start chemotherapy (using the drug Capecitabine) instead.

This trial was conducted with an aim of seeing if treating these women with Trastuzumab as well as Capecitabine (the chemotherapy drug) was a better option rather than stopping Trastuzumab and using only Capecitabine.

This trial was done by Dr. R Stein and Dr. T Perren, with support from Cancer Research UK, Clinical Trials Research Unit (CTRU), University of Leeds, German Breast Group (GBG), National Institute for Health Research Cancer Research Network (NCRN) and Roche.

A total of 156 women with locally advanced cancer (cancer which had come back in the breast area) or metastasized cancer (cancer which has spread to other parts of the body) were enrolled in the trial. All these women had been treated with Trastuzumab but cancer had started to grow again in them after treatment. These 156 women were divided into 2 equal groups having 78 participants each:

  • Group 1 participants were given only Capecitabine
  • Group 2 participants were given Capecitabine as well as Trastuzumab

After a 2-year follow-up period, treatment response was measured in the participants of the trial.

Capecitabine and Trastuzumab combination treatment

More Group 2 participants i.e. those given Capecitabine + Trastuzumab showed good treatment response in terms of reduction in their cancer compared to Group 1 who were given only Capecitabine (ref: above Graph).

Capecitabine and Trastuzumab combination treatment

Average duration before cancer started growing again i.e. duration of disease free survival was higher in the group which was given both drugs compared to the group given Capecitabine alone (ref: Graph 2). The women in the group receiving Capecitabine + Trastuzumab did not have any more side effects than those who had Capecitabine alone.

At the end of 3 years, survival among the participants in both treatment groups was seen again. Group 2 (Capecitabine + Trastuzumab) had a better average survival than Group 1 (Capecitabine alone). Also, the women who started (or continued) taking Trastuzumab even after their cancer started to grow again did better than those who didn’t.

The researchers concluded that the combination of Capecitabine and Trastuzumab was better at stopping cancer growing than Capecitabine alone.

Is the combination of Exemestane & Everolimus more effective than Exemestane alone in treating Oestrogen Receptor Positive Advanced Breast Cancer that has spread 31

The type of breast cancer which is sensitive to the female hormone Oestrogen is known as Oestrogen Receptor Positive Breast Cancer. For treatment of this type of cancer, doctors commonly use hormone therapy. Commonly used hormone therapy drugs are Letrozole and Anastrozole. However, in some cases, even after this treatment, the cancer continues to grow or comes back after some improvement. The treatment to be given in these cases is under research.

In this trial, all patients who met the above criteria were undergoing hormone therapy using the drug Exemestane. Some patients were given biological therapy using the drug Everolimus in addition to Exemestane (hormone therapy). This was done in order to compare the effect of using only hormone therapy (Exemestane) and combining it with biological therapy (Everolimus) in breast cancer patients whose cancer had come back or continued to grow even after treatment with Letrozole and Anastrozole.

This trial was thus conducted by Professor Robert Coleman in collaboration with the National Institute for Health Research Cancer Research Network (NCRN) and Novartis.

The researchers enrolled 724 postmenopausal women who had oestrogen receptor positive, advanced breast cancer who were randomly divided into two treatment groups. All these women had undergone hormone therapy and many of them had also undergone chemotherapy.

  • Group 1 included 485 women who were given Exemestane + Everolimus
  • Group 2 included 239 women who were given

Exemestane + Placebo (participants thought they were receiving the drug but were actually given a dummy drug)

After about 18 months of follow-up, the average progression free survival of these women was calculated. Progression free survival is defined as the duration for which the patient’s cancer did not progress (grow) after treatment.

As can be seen from the above graph, Group 1 patients had higher average progression free survival than Group 2 patients. However, Group 2 patients also showed presence of more side effects such as fatigue (tiredness, shortness of breath), anemia (reduction in red blood cells) and Sore mouth (irritation in mouth area).

In conclusion, combination treatment of Exemestane and Everolimus was more effective than Exemestane alone in prolonging progression free survival (i.e. survival without cancer getting worse) among women suffering from oestrogen positive advanced breast cancer.

Does Epirubicin increase the chances of long term heart problems in women who were treated with the drug for Breast Cancer? 32

A common chemotherapy drug used in treatment of many types of cancers, including breast cancer is Epirubicin. It is safe and highly effective which is the reason behind its widespread usage. However, in some patients, use of Epirubicin is seen to be accompanied by certain side effects which include impairment in the heart pumping mechanism. This poses a potential risk of long term heart damage people taking this drug.

This trial was thus conducted by Professor Hugh Montgomery with support from Department of Health, Experimental Cancer Medicine Centre (ECMC), Imperial College London, National Institute for Health Research Cancer Research Network (NCRN) and the University College London (UCL) to find out the factors which made certain people more likely to develop long term heart damage by Epirubicin usage.

A group of 164 women suffering from breast cancer and taking Epirubicin for its treatment were observed as part of this trial. Useful information was obtained by studying these womens’ heart scans, blood tests and urine test results. Before beginning treatment with Epirubicin, the Cardiovascular Magnetic Resonance scan (CMR scan) of these women was taken to assess the pumping efficiency of their hearts. This scan enables doctors to see how much blood is pumped with each heartbeat. This scan was repeated after chemotherapy treatment ended. Some women were also made to undergo this scan after first dose of chemotherapy in addition to the scan at the end of chemotherapy.

Researchers said that the scans at after first dose of chemotherapy could show changes to the heart which may help in identifying those women who are at a higher risk of long term heart damage after completion of chemotherapy.

Results of the trial showed that in 21% of the women, the amount of blood pumped out by the heart had fallen by 5% or more which was indicative of heart damage. It should be noted here that on an average, these women (21%):

  • weighed more,
  • were more likely to have high blood pressure and
  • had higher percentage body fat as compared to the women who did not show 5% or more fall in the amount of blood pumped out by the heart.

Around 10% of the women who were involved in this study had high blood pressure for which these women were not taking any medicine/other treatment. These hypertensive women (women having high blood pressure) were more likely to have changes to their heart after being treated with Epirubicin.

This trial reports that in the given groups of women who took Epirubicin as treatment for breast cancer, 21% had an a minimal(5%) degradation in the blood pumping capacity of their heart. It was found that the women who exhibited this degradation were more likely people who originally had high blood pressure and/or were overweight with high percentage of body fat.

Researchers, therefore identified high blood pressure as a factor which encouraged heart damage as a side effect of Epirubicin. It is therefore recommended for patients who are about to start treatment with Epirubicin to bring their blood pressure under control by treatment before starting Epirubicin.

Is Lapatinib + Paclitaxel better than Paclitaxel alone in Treating Advanced or Metastatic Breast Cancer? 33

A clinical trial conducted by GlaxoSmithKline in 2013 aimed to compare the treatment benefit of Paclitaxel used with Lapatinib compared to Paclitaxel alone on women with advanced or metastatic breast cancer.

579 women with advanced or metastatic breast cancer (cancer which had spread to other parts of the body) were enrolled in this study and were randomly divided into 2 treatment groups. Neither the researchers nor the participants could decide which group they would be put into.

Additionally, neither of them knew which group was being given which treatment. This type of research study is called Double-Blind Randomized Study. This is done in order to avoid any bias on part of researcher and participants to ensure accurate, reliable results of the trial.

The two treatment groups were as follows:

  • Group 1 had 291 participants who were given Paclitaxel + Lapatinib
  • Group 2 had 288 participants who were given Paclitaxel + Placebo (Placebo means – patient is under impression that she is receiving actual drug but is actually being given a dummy drug which does not have the effects of actual drug. This is done to know the psychological effect on health of patients who are taking dummy drug with belief that it is actual drug versus health effects on patients taking actual drug).

At the end of the trial, researchers found out how many participants in each group had shown clinical benefit from treatment. Clinical benefit included: stability in disease i.e. no improvement or worsening in cancer, reduction in cancer or complete disappearance in all signs of cancer.

They also observed how long the women in both groups kept showing treatment response (improvement in their condition due to treatment). Progression Free Survival i.e. duration for which patient survived without increase in cancer as well as Overall Survival (duration for which Patient lived with or without increase in cancer) was calculated to compare the effects of both treatments on survival rates.

Lapatinib and Paclitaxel combination treatment

Considerably more women in Group 1 had reduction, disappearance or stability in cancer after treatment (ref above Graph).

Lapatinib and Paclitaxel combination treatment

Women who were given both Paclitaxel and Lapatinib continued to show benefit from treatment for longer time period than those given only Paclitaxel. Also, their tumor grew slower than the Paclitaxel group and they lived longer, with and without tumor growth than Group 2.

Lapatinib and Paclitaxel work better than Paclitaxel alone in improving prognosis among women with advanced or metastatic breast cancer.

Lapatinib vs Trastuzumab – which is a better when combined with standard chemotherapy drugs (docetaxel & paclitaxel) to treat HER2 +ve Metastatic Breast Cancer 34

Breast cancer cells have many growth factor receptors which, when triggered, cause these cells to divide and increase in number. One of these receptors is HER2 and those patients who have breast cancer which produces excess of HER2 are called HER2 positive breast cancer.

Women who have previously not been treated for their metastatic breast cancer (breast cancer which has spread to other parts of the body) and have HER2 positive breast cancer are usually treated using Taxane based chemotherapy (chemotherapy using drugs belonging to the group ‘Taxanes’ like Docetaxel and Paclitaxel) along with a drug called Trastuzumab.

Trastuzumab is an antibody that is given through a vein in the arm and it works by blocking the action of the receptor HER2. However, this treatment is not effective in all such patient. In some of these patients the cancer may start to grow again.

Lapatinib is a new drug which also target the HER2 receptor, thus stopping or slowing down the growth and spread of cancer. But, Lapatinib is not an antibody like Trastuzumab. It is a pill which is to be taken by mouth on a daily basis.

This trial conducted by NCIC Clinical Trials Group and GlaxoSmithKline aimed to compare the effect of using Lapatinib with Taxane based chemotherapy versus using Trastuzumab with Taxane based chemotherapy on the prognosis in women with HER2 positive, metastatic breast cancer.

Nearly 650 women with HER2 positive, metastatic breast cancer were made a part of this study. They were divided into 2 treatments groups.

  • Group 1 was given Lapatinib + Docetaxel/Paclitaxel
  • Group 2 was given Trastuzumab + Docetaxel/Paclitaxel

The results were seen in terms of progression free survival (duration for which patient lives without increase in cancer), overall survival (duration for which patient lives with or without increase in cancer), Objective Response Rate (percentage of patients in whom the cancer decreases or disappears) as well as Quality of Life scores as rated by patients themselves using a questionnaire given to them.

Lapatinib vs Trastuzumab

The median duration of progression free survival (PFS) for Group 1 was 9.13 months which means that half the women of this group lived without worsening of disease for 9.13 months or more. The shortest duration of PFS was 0.0 months while some women also lived up to 32.69 months. By comparison, the median duration of PFS (13.63 months) as well as highest duration (38.54 months) was more for Group 2.

Even the median duration of overall survival was higher for Group 2 (21.8 months) compared to Group 1 (20.8 months). In Group 1, shortest duration of overall survival was 14.2 months while longest was 31.3 months. For Group 2, these durations were 14.3 months and 30.6 months respectively.

From this, we can see that the group which received Trastuzumab had longer ‘controlled cancer’ period and also survived longer overall.

Lapatinib vs Trastuzumab

Above graph shows that slightly more participants in Group 2 (Trastuzumab + Chemotherapy) had a reduction or disappearance of their cancer compared to the other group.

Capecitabine and Trastuzumab combination treatment Lapatinib vs Trastuzumab

The group who was given Trastuzumab + Chemotherapy rated their quality of life higher than those who were given Lapatinib + Chemotherapy (ref: above Graph).

The results of this trial suggest that Trastuzumab + Chemotherapy shows slightly better prognosis, survival and quality of life than Lapatinib + Chemotherapy in HER 2 positive metastatic breast cancer patients.

Efficacy analysis of Gene Therapy combined with Chemotherapy to treat Breast Cancer nodules in the Skin 35

Women suffering from early breast cancer generally undergo chemotherapy after surgery to reduce chances of recurrence (re-occurrence of cancer). A clinical trial was conducted to see if addition of the drug Docetaxel (Taxotere) in such patients (along with on-going chemotherapy) would improve treatment outcome and reduce chances of recurrence in patients.

This trial was conducted by Dr. Paul Ellis and Professor Peter Barrett-Lee in collaboration with Cancer Research UK, Experimental Cancer Medicine Centre (ECMC), Guy’s and St Thomas’ NHS Foundation Trust, Institute of Cancer Research (ICR), National Institute for Health Research Cancer Research Network (NCRN), Scottish Cancer Research Network, Wales Cancer Trials Breast Group, Yorkshire Breast Cancer Group.

The trial involved 4162 women who were divided into 3 groups.

  • Group 1 was given FEC chemotherapy and Docetaxel
  • Group 2 was given only FEC chemotherapy
  • Group 3 was given only ECMF chemotherapy

FEC chemotherapy and ECMF chemotherapy are standard chemotherapy procedures, commonly used in treatment of breast cancer. They use the following drugs:

FEC -Fluorouracil, Epirubicin and Cyclophosphamide &

ECMF – Epirubicin, Cyclophosphamide, Methotrexate and Fluorouracil respectively.

MetXia treatment

Cancer response was also observed in patients and it was seen that while the cancer stayed the same or got smaller in 2 participants (25%), it continued to grow in 6 participants (75%).

MetXia was safe to use and it was able to carry the gene into the cancer cells. These results are encouraging and holds potential in treating cancer which has spread to the skin.

Effectiveness of Exemestane versus Celecoxib in Treatment of Ductal Carcinoma in Situ (DCIS) 36

Ductal Carcinoma in Situ (DCIS) is an initial form of breast cancer in which the cells in the ducts of breast become damaged or cancerous. If not treated, it may develop into invasive breast cancer. DCIS is generally treated with surgery. Hormone therapy using the drug Tamoxifen is usually used to prevent development of breast cancer in women with DCIS. However, Tamoxifen fails to act with good effectiveness in some women with DCIS.

This fact prompted researchers to look at the effect of another hormone therapy drug (Exemestane) and a biological therapy drug (Celecoxib) in treating women with DCIS.

Hormone therapy acts by stopping production of hormones such as oestrogen and progesterone which encourage growth of cancer cells. Biological therapy works by blocking the action of proteins which play a role in division and thus increase in number of cancer cells.

90 women took part in this trial. They were divided into 2 treatment groups.

  • Group 1 was given Exemestane
  • Group 2 was given Celecoxib

All the participants were given these treatments (drugs) for a period of 2 weeks. They were given in the time frame between diagnosis and surgery. Later, the cells removed during surgery were studied to see the effect of the 2 different treatments on them.

This trial was conducted by Professor Nigel Bundred, in collaboration with Celecoxib Oncology Research in Europe (CORE), National Institute for Health Research Cancer Research Network (NCRN), University Hospital of South Manchester (UHSM) and the University of Manchester.

The researchers studied the following as part of results:

  • Number of cells dying off
  • How much HER2 is present: HER2 (Human Epidermal Growth Factor Receptor) is a protein found in small amounts on some normal cells, including breast cells, stomach cells and bladder cells. It is one of the proteins involved in cell growth.
  • Amount of Ki67 protein present in cells: Ki67 is a protein which is present in cells when they are dividing and thus increasing total number of cells.

Women who were given Exemestane had less Ki67 in the cells removed during surgery compared to cells taken during biopsy, suggesting that fewer cells were dividing after treatment with Exemestane. On the other hand, in women who were given Celecoxib, number of cells dividing or dying off remained same.

Trial results suggest that Exemestane is more effective than Celecoxib in treating Ductal Carcinoma in Situ (DCIS).

How Effective is Lapatinib in HER2 negative Breast Cancer 37

Lapatinib is an anti-cancer drug which has been shown to slow or stop cancer cells from growing. It acts by blocking the activity of growth receptors which are present on cancer cells and play a role in growth and division of cancer cells. Lapatinib blocks the activity of 2 such receptors: EGFR (Epidermal Growth Factor Receptor) and HER2 (Human Epidermal Growth Factor Receptor). The type of cancer in which cancer cells have large amounts of HER2 are known as HER2 positive cancer.

In this trial, researchers wanted to see if Lapatinib works well on breast cancers which are not HER2 positive i.e. do not possess large amounts of HER2. They also wanted to know about the side effects of this treatment.

Professor Charles Coombes carried out this clinical research study with the help of Cancer Research UK, Experimental Cancer Medicine Centre (ECMC), GlaxoSmithKline (GSK), Imperial Clinical Trials Unit – Cancer (ICTU-Ca), Imperial College London and the National Institute for Health Research Cancer Research Network (NCRN).

The trial was completed with 25 breast cancer patients, all of whom were given 4-6 weeks of Lapatinib before surgery. Ultrasound scan was done for these women before starting Lapatinib and once again after end of treatment. This was done to see the change in the size if the cancer.

effectiveness of Lapatinib in HER2 negative cancer

 

Encouraging results emerged from the trial. In majority of patients, the cancer either remained stable or reduced but also kept growing in 16% of the women (ref: Graph).

Common side effects suffered by women in this study are listed below:

  • Tiredness
  • Diarrhea
  • Skin rash, itchy skin
  • Drop in red blood cells (anemia – may lead to tiredness)
  • Adverse effect on normal working of liver
  • Abdominal pain
  • Wheezing (little difficulty in breathing)

Researchers concluded that overall, Lapatinib had some effect on HER2 negative breast cancer cells but nowhere near as effective as it is with HER positive breast cancer.

Clinical Trial comparing the treatment response given by Advanced Breast Cancer Patients to Letrozole and Lapatinib versus Letrozole alone 38

Breast cancer treatment generally includes surgery along with the following treatments either in alone or in combination with each other: chemotherapy, radiation, hormone therapy or biological therapy. However, in some cases, despite these treatments, the breast cancer comes back or spreads to other body parts. This is advanced breast cancer.

Letrozole is a hormone therapy drug frequently used for treating advanced breast cancer. It acts by stopping the production of the female hormone Oestrogen which contributes to growth of cancer cells. Researchers wished to compare the effects of using Letrozole alone versus using it in combination with a relatively newer drug called Lapatinib.

Breast cancer cells have many growth factor receptors on them which, on receiving stimulus, signal the cancer cells to divide and thus increase in number, causing the breast cancer to grow and spread. Lapatinib acts by targeting 2 such receptors: EGFR (Epidermal Growth Factor Receptor) and HER2 (Human Epidermal Growth Receptor Factor). The type of cancer where the cancer cells have a large amount of HER2 are called HER2 positive cancer and those which do not have large amount of HER2 are called HER2 negative cancer.

The fact that Lapatinib would target 2 receptors simultaneously led the doctors to believe that it could lead to better treatment response in advanced breast cancer. So they conducted this trial to see if Lapatinib and Letrozole was better than Letrozole alone in treating advanced breast cancer. The trial was done by Professor Neville Davidson in association with GlaxoSmithKline (GSK).

A total of 1286 advanced breast cancer patients were enrolled in the trial. They were randomly divided into 2 treatment groups.

  • Group 1 had 643 participants who were given Letrozole + Lapatinib
  • Group 2 had 643 participants who were given Letrozole + Placebo (Placebo means – patient is under impression that she is receiving actual drug but is actually being given a dummy drug which does not have the effects of actual drug.
  • HER2 positive and HER2 negative cancer patients were identified. 219 had HER2 positive cancer while 952 participants had HER2 negative cancer.

Letrozole and Lapatinib

Letrozole and Lapatinib

The trial results showed a better impact of Letrozole + Lapatinib in the participants compared to Letrozole alone. This effect was more prominent in HER2 Positive patients.

Letrozole in combination with Lapatinib is recommended over use of Letrozole alone in treatment of advanced breast cancer, particularly in HER2 positive cancer patients.

Evaluating the effectiveness of Ixabepilone when given after Chemotherapy Vs Standard Treatment (Paclitaxel) before surgery in Early Stage Breast Cancer 39

Early stage breast cancer is often treated with surgery. In cases where the tumor is too large to be operated on, chemotherapy is given before surgery to reduce the size of the tumor after which surgery is done.

This trial compared the effectiveness of the drug Ixabepilone when given after chemotherapy (using Doxorubicin and Cyclophosphamide) versus standard treatment drug (Paclitaxel) after chemotherapy in patients with early stage breast cancer.

Bristol-Myers Squibb conducted this trial in 2011 on 295 women with early stage breast cancer. They were randomly divided into 2 treatment groups. The researchers or participants could not decide which participant would be put into which group:

  • Group 1 had 148 women who were given Ixabepilone
  • Group 2 had 147 women who were given Paclitaxel

Ixabepilone with paclitaxel

Clinical Objective Response means positive response to treatment in terms of disappearance or substantial reduction in cancer among patient. More women who were given Ixabepilone responded favorably to treatment than those who were given Paclitaxel (ref: Graph).

Results of the trial suggest that Ixabepilone may be more effective than Paclitaxel and should thus be considered as a treatment option in such situations. However, side effects need to be actively considered before doing so.

Clinical Trial Assessing the Long Term Benefits of Tamoxifen Treatment for Women Older than 50 years who have Undergone Breast Cancer Surgery 40

In women who have undergone breast cancer surgery, doctors often administer Tamoxifen (a hormone therapy drug) to prevent cancer recurrence (cancer coming back). However, long term effects of Tamoxifen in such women were not previously explored.

Professor Michael Baum, in association with the Cancer Research UK conducted a clinical trial on 3449 women, more than 50 years of age, who had already undergone breast cancer surgery.

A little more than half of these women (52%) were postmenopausal (i.e. had already passed through menopause). All these women were given Tamoxifen for 2 years after surgery. After this, they were randomly divided into 2 treatment groups:

  • Group 1 included 1724 participants who stopped taking Tamoxifen after 2 years.
  • Group 2 included 1725 participants who continued Tamoxifen for 3 more years i.e. took Tamoxifen for a total of 5 years.

These women were followed up for almost 10 years from start of treatment and researchers found out how many women had a recurrence of cancer (cancer had come back) or developed in the other breast.

Tamoxifen after Breast Cancer surgery

The graph above shows that cancer returned or developed in the other breast for more women in Group 1 (Tamoxifen – 2 years) compared to Group 2 (Tamoxifen – 5 years).

Researchers also found that taking Tamoxifen for 5 years reduced the risk of heart disease among these women, the effect being strongest in women between 50 and 59 years of age.

In conclusion, taking Tamoxifen for 5 years reduced the risk of cancer coming back or developing in the other breast. Thus, researchers recommend that women should be encouraged to complete full 5 years of Tamoxifen treatment after breast cancer surgery.

Can Tamoxifen prevent Breast Cancer in women who are at high risk 41

The risk of breast cancer increases in a woman if she has a family history of the same (one or more close relatives have had breast or ovarian cancer). In such cases, preventive measures become crucial to avoid occurrence of breast cancer in these women.

In this trial supported by Cancer Research UK, Professor Jack Cuzick compared the effect of Tamoxifen (a type of hormone therapy drug commonly used in treatment of breast cancer) to a placebo (dummy tablet) to see if it can reduce the risk of developing breast cancer in high risk women (those having family history).

The trial enrolled 7154 women who were at high risk of getting breast cancer in the future due to family history. They were divided into 2 treatment groups:

  • Group 1 (3579 participants) was given Tamoxifen daily for 5 years
  • Group 2 (3575 participants) was given placebo (the patients are given a dummy tablet but are under impression that they are receiving actual drug) daily for 5 years

 

After 10 years, the research team found out how many women in each treatment group had developed cancer.

tamoxifen breast cancer prevention

Overall, a small percentage of the women who were at risk of developing breast cancer developed the disease. This percentage was higher in the group that was not given Tamoxifen compared to those who took the drug (ref: Graph).

With regards to side effects, the Tamoxifen group did have more side effects compared to placebo group but these side effects reduced or disappeared when the women stopped taking Tamoxifen after 5 years.

A preventive treatment of Tamoxifen, taken for 5 years, successfully reduces the risk of breast cancer in women who are at high risk of developing it owing to family history.

Is taking Tamoxifen for 10 years more effective than taking it for 5 Years in Early Stage Breast Cancer Patients? 42

The anti-cancer drug Tamoxifen is widely used in treatment of women who have early stage breast cancer to prevent recurrence (cancer coming back) among them. Generally, this drug is taken for a period of 5 years. In this trial, researchers find out if taking this drug for twice as long (10 years) gave a better treatment response than taking it for 5 years.

This trial was undertaken by Dr. Daniel Rea and Professor Richard Gray with help from Cancer Research UK, Medical Research Council (MRC), National Institute for Health Research Cancer Research Network (NCRN) and the University of Birmingham.

A total of 6953 women who were already taking Tamoxifen since the past 4 years were enrolled in the clinical trial. They were put into 2 treatment groups where the first group stopped taking Tamoxifen after 5 years while the other group continued Tamoxifen for a total of 10 years.

Tamoxifen 5 yr or 10 yr treatment

Much more women who took Tamoxifen for shorter period (5 years) developed cancer again or died due to breast cancer compared to those women who took Tamoxifen for 10 years

The beneficial effects of Tamoxifen are accompanied by a possible side effect: increased risk of womb cancer. Researchers also studied this aspect of the treatment and found out how many women in each treatment group suffered from womb cancer and how many died due to it.

Tamoxifen 5 yr or 10 yr treatment

Overall, a very small percentage of women in both groups developed womb cancer and an even smaller number of them died due to it. Although more women in the group which took Tamoxifen for 10 years got womb cancer compared to the other group, number of deaths was smaller in this group.

Womb cancer can be successfully treated, provided it is diagnosed early and thus does not pose a very serious death risk to these women who may develop it as a side effect of Tamoxifen. Tamoxifen, on the other hand, would help them avoid a recurrence of breast cancer which is more difficult to treat than womb cancer.

The researchers concluded that taking Tamoxifen for 10 years reduced the risk of breast cancer recurrence.

Comparing the effectiveness of Lapatinib versus Trastuzumab when used with Capecitabine in Treatment of HER2 Positive Metastatic Breast Cancer that spread to the brain 43

Breast cancer is normally treated with certain groups of drugs which have shown to be effective anticancer medicines. These include a groups of drugs called Anthracyclines and Taxanes. However, sometimes, the cancer does not respond as expected to these drugs and other drugs or drug combinations may need to be used by doctors. This is especially true in cases where the cancer has spread to other parts of the body, even after treatment.

Breast cancer cells have many growth factor receptors which, when triggered, cause these cells to divide and increase in number. One of these receptors is HER2 and those patients who have breast cancer which produces excess of HER2 are called HER2 positive breast cancer.

In this trial, conducted by GlaxoSmithKline in 2014, researchers wanted to compare the effects of two drug combinations in HER 2 positive breast cancer patients whose cancer had spread to the brain. Lapatinib, Capecitabine and Trastuzumab are commonly used effective anti-cancer drugs which the researcher used in 2 different combinations and observed their effects in the patients.

The researchers enrolled 540 women with HER2 positive breast cancer which had spread to their brain. These participants were then divided into 2 treatment groups, randomly. Neither the researcher nor the participants themselves could decide which treatment group they would be in.

  • Group 1 had 271 participants who were given Lapatinib + Capecitabine
  • Group2 had 269 participants who were given Trastuzumab + Capecitabine

Treatment response and duration of survival, with or without any increase in cancer was measured for all these women. The following aspects were studied by researchers:

  • Complete Response – disappearance of cancer
  • Partial Response – reduction in cancer
  • Stable Disease – no change in cancer (no increase or decrease)
  • Duration of Response – average time period for which the patients showed complete/partial response to treatment
  • Progression Free Survival – average duration for which patients lived without any increase in cancer
  • Overall Survival – average duration for which patients lived with or without any increase in cancer

Treatment response when Lapatinib or Trastuzumab is prescribed with Capecitabine for advanced breast cancer

Very few women gave complete response to treatment. This percentage, was however, larger for the group which was given Trastuzumab + Capecitabine. Similarly, partial response and stable disease was also seen more among women in Group 2.

Treatment response when Lapatinib or Trastuzumab is prescribed with Capecitabine for advanced breast cancer

Also, Group 2 responded for longer to the treatment, had longer progression free survival and lived longer overall (ref: above Graph).

Trastuzumab and Capecitabine used in combination could be a better treatment option compared to Lapatinib and Capecitabine in these women.

Lapatinib in combination With Trastuzumab Vs Lapatinib Monotherapy in HER2-positive Metastatic Breast Cancer patients 44

A clinical trial was conducted by GlaxoSmithKline in 2012 to compare the effectiveness of using Lapatinib alone versus in combination with Trastuzumab in treatment of HER2 positive metastatic breast cancer.

Breast cancer cells have many growth factor receptors which, when triggered, cause these cells to divide and increase in number. One of these receptors is HER2 and those patients who have breast cancer which produces excess of HER2 are called HER2 positive breast cancer. Metastatic breast cancer is the type of cancer which has spread to other parts of the body.

291 women suffering from metastatic breast cancer were made a part of this clinical trial. They were put into 2 treatment groups randomly i.e. neither researchers nor participants could decide which groups they would be a part of.

  • Group 1 had 146 participants who were given Lapatinib + Trastuzumab
  • Group 2 had 145 participants who were given only Lapatinib

Treatment Response of participants was measured in terms of:

  • Complete/Partial Response – reduction or disappearance of cancer
  • Stable Disease – no change (increase or decrease) in cancer.

The average Progression Free Survival (duration for which patient lived without increase in caner) as well as Overall Survival (duration for which patient lived with or without increase in cancer) was also measured.

 

Lapatinib and Trastuzumab combination treatment to treat HER2 +ve cancer

It is clear from the above Graph that women in Group 1 (Lapatinib + Trastuzumab) gives better treatment response than Group 1. More women in Group 1 had a reduction/disappearance/stability in their cancer compared to the other group.

Lapatinib and Trastuzumab combination treatment to treat HER2 +ve cancer

Women who were given both Lapatinib and Trastuzumab (Group 1) had a higher median duration of progression free survival (PFS) compared to Group 2. The median duration of PFS for Group 1 was 12 weeks which means that 50% of the women of this group lived without disease progression for 12 weeks or more than that. The lowest PFS was 8.1 weeks while some women also lived free of progression for up to 16 weeks.

In Group 2 the median duration of PFS was 8.1 weeks. Lowest (7.6 weeks) and highest (9 weeks) duration of PFS were also lower than Group 1.

The researchers also found out the median durations of Overall Survival (OS) among women in both groups. OS indicates the duration for which the women lived, with or without any aggravation of their disease.

In Group 1, half of the women lived for at least 51.6 weeks while in Group 2 this duration was only 39 weeks. Lowest and highest duration of OS were also higher for Group 1. For Group 1 these were 42.9 weeks and 57.3 weeks while for Group 2; 32.9 weeks and 52.1 weeks.

Combination of Lapatinib and Trastuzumab proved more powerful than Lapatinib alone in treating women with HER2 +ve metastatic breast cancer.

Does Pertuzumab work in treating Metastatic Breast Cancer with Low or Medium Level of HER2? 45

Breast Cancer is generally treated with either one or combination of one or more of these treatments: surgery, radiation, chemotherapy and hormone therapy. However, sometimes, after treatment, the cancer spreads outside the breast or reoccurs (comes back) in another part of the body. This type of cancer is called metastatic breast cancer.

Also, sometimes the cancer cells contain large amount of a protein called HER2 which is responsible for stimulating growth and division of cancer cells. The type of cancer where the cancer cells have a large amount of HER2 is called HER2 positive breast cancer. Pertuzumab is a type of biological therapy drug which acts by targeting HER2 and thus restricting cancer growth.

Researchers – Dr. David Cameron, Dr. Andrew Wardley and Dr. David Miles wanted to see the effect of Pertuzumab on metastatic breast cancer with low or medium amount of HER2. Thus they conducted this trial with support from Roche.

77 women with metastatic breast cancer took part in this trial. They were divided into two treatment groups:

  • Group 1 had 41 women who were given a low dose of Pertuzumab once every 3 weeks
  • Group 2 had 37 women who were given a high dose of Pertuzumab once every 3 weeks

Low dose Pertuzumab treatment results

High dose Pertuzumab treatment results

On comparing the above two graphs, it is clear that in neither of the groups was there a significant number of women whose cancer reduced. Few women (5) experienced side effects such as dizziness, rash, chills, fever and shortness of breath when Pertuzumab injection was given to them. Other side effects included diarrhea, sickness and weakness.

Researchers concluded that Pertuzumab was not very helpful in treating metastatic breast cancer patients with low or moderate levels of HER2.

Comparing two different ways of prescribing the Anti-Cancer Drugs: Docetaxel, Doxorubicin and Cyclophosphamide to operable HER2neu Negative Breast Cancer Patients with +ve axillary lymph nodes 46

Sanofi and the Cancer International Research Group carried out a clinical research trial in 2013 in women suffering from operable breast cancer to compare the effects of two different treatment regimens on disease free survival and overall survival among them.

A total of 3298 women suffering from breast cancer were made part of the trial and randomly divided into 2 equal treatment groups. Neither researchers nor the women in the trial could decide which group they would be put into. This is called Randomization and is done to avoid any type of bias from researcher or trial participants.

  • Group 1 had 1649 participants who were given Doxorubicin and Cyclophosphamide combination followed by Docetaxel
  • Group 2 had 1649 participants who were given Docetaxel and Doxorubicin combination followed by Cyclophosphamide

Docetaxel, Doxorubicin and Cyclophosphamide treatment results

Researchers followed-up the participants for about 65 months and found out in how many of them cancer had returned or new cancer had developed, how many women had died. Presence of serious adverse events due to treatment were also found out.

While the number of women who had returned or new cancer or death was almost same in both groups, more women in the second group died by the end of 65 month. Additionally, severe side effects were also more common in Group 2.

Prescribing Docetaxel after Doxorubicin and Cyclophosphamide may not be decisively better but certainly induced fewer adverse effects in this study.

Is Trastuzumab helpful in women with HER2 positive early breast cancer? 47

HER2 is a protein found in small amounts on some normal cells, including breast cells, stomach cells and bladder cells. It is one of the proteins involved in cell growth. Some cancers have cells with large amounts of this protein and such cancers are called HER2 positive.

The presence of HER2 in large amounts in cancer cells enhances the growth of these cells and thus become responsible for spreading the cancer. These HER2 positive cancers can be treated with drugs that target the HER2 protein. One such drug is Trastuzumab.

Keeping this in mind, a trial was conducted by Professor Ian Smith in collaboration with Breast International Group (BIG), Cancer Research UK, Experimental Cancer Medicine Centre (ECMC), National Institute for Health Research Cancer Research Network (NCRN) and Roche to study the effect of administering the drug Trastuzumab (Herceptin) in women with HER2 positive early stage breast cancer and also looking at the side effects of this treatment.

A total of 5100 women who had previously undergone chemotherapy and possibly, radiation for HER2 positive early breast cancer were enrolled in the clinical trial. They were divided into 3 equal groups, containing 1700 participants each:

  • Group 1 was given Trastuzumab every 3 weeks for one year
  • Group 2 was given Trastuzumab every 3 weeks for 2 years
  • Group 3 was not given Trastuzumab at all.

Trastuzumab HER2 Breast Cancer Treatments

Graph above indicates that the group that was given Trastuzumab for a year gave better treatment response compared to the group that was not given Trastuzumab in terms of recurrence of cancer (cancer coming back), cancer in the other breast, development of other type of cancer or death.

When the side effects of the drug Trastuzumab were looked at, the most important one was adverse effects on the heart.

Trastuzumab HER2 Breast Cancer Treatments

Looking at Graph, it is evident that more participants who were given Trastuzumab suffered adverse effects on their heart as compared to the other participants.

After following up these women for 6 years, researchers have confirmed that using Trastuzumab for either 1 or 2 years is beneficial. While there was no significant difference in the number of women living disease free in both groups (those given Trastuzumab for 1 year and 2 years), more women who were given the drug for 2 years had side effects.

1 year of Trastuzumab is widely recommended treatment for women with HER2 positive early breast cancer.

Comparing Two Standard Chemotherapy Regimens in Treatment of Node Positive, Operable Breast Cancer 48

Node-positive breast cancer means that cancer cells from the tumor in the breast have been found in the lymph nodes (sometimes called “glands”) in the armpit area. This trial was conducted by Sanofi and the Cancer International Research Group in 2011 with an aim of finding out which of the following two standard chemotherapy treatments was more beneficial to patients of node positive operable breast cancer:

  • Treatment 1: Docetaxel + Doxorubicin + Cyclophosphamide
  • Treatment 2: Fluorouracil + Doxorubicin + Cyclophosphamide

1491 women with node positive operable breast cancer were enrolled in this trial. They were then randomly divided into 2 treatment groups. Neither researchers nor the women in the trial could decide which group they would be put into. This is called Randomization and is done to avoid any type of bias from researcher or trial participants.

  • Group 1 included 745 participants who were given Treatment 1
  • Group 2 included 746 participants who were given Treatment 2

The researchers followed up these participants for almost 10 years and found out, in how many women, there was a return of cancer, development of new cancer or death. Side effects experienced by women in both group were also measured.

Docetaxel + Doxorubicin + Cyclophosphamide VS Fluorouracil + Doxorubicin + Cyclophosphamide

Women in the first treatment group gave better response to treatment. Fewer of them had recurrence (coming back) or growth of cancer as well as development of new cancer or death compared to second group. However, they also faced serious side effects more commonly than the other group.

In conclusion, the treatment including Docetaxel seems to benefit node positive breast cancer patients more than the treatment which included Fluorouracil – but the side effects with Docetaxel were considerable.

Comparing the effectiveness of two different Radiotherapy dosage and frequency in Treatment of Early Stage Breast Cancer 49

Early stage breast cancer is most commonly treated with surgery which is followed by treatments such as radiotherapy and chemotherapy to reduce risk of the cancer coming back.

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Radiation Therapy

This trial explores the comparative effects of two different radiotherapy schedules in women who have undergone breast cancer surgery. The way in which radiotherapy is given; number of doses, quantity of each dose, is known as ‘radiotherapy schedule’. A radiotherapy dose is measured in units called ‘grays’.

Professor John Yarnold carried out this trial in collaboration with Cancer Research UK, Department of Health, Institute of Cancer Research (ICR), Medical Research Council (MRC) and the National Institute for Health Research Cancer Research Network (NCRN).

The trial included 2215 women who had undergone breast cancer surgery. They were divided into two groups containing about 1100 participants each.

  • Group 1 was given radiotherapy 5 times a week for 5 weeks, with a total dose of 50 gray in 25 doses of 2 gray.
  • Group 2 was given radiotherapy 5 times a week for 3 weeks, with a total dose of 40 gray in 15 doses of 2.67 gray.

The participants were followed up for 6 years after which, number of women with cancer recurrence was found out.

optimal radiotherapy schedule finding

Cancer came back in more women of Group 1compared to Group 2. However, overall recurrence rate was very low in both groups. Side effects such as pain in arm and shoulder were reported by 1/3rd of the women involved in the trial.

Photographs of the participants’ breasts were taken before and after treatment. On comparing these, researchers found that fewer women in Group 2 had changes in the appearance of their breast compared to Group 1. When asked, women in Group 2 themselves also reported less changes in the appearance of their breast compared to Group 1.

These women were followed up again after 10 years. Number of women whose cancer had returned in the breast was similar in both the groups and fewer adverse changes in the breast were reported by Group 2 participants.

Both schedules gave excellent results for early stage breast cancer patients in this study, with marginal difference that could be due to chance. Researchers concluded that both the radiotherapy schedules worked equally well in improving quality of life and disease free survival among women who had undergone breast cancer surgery, but the lesser side effects in the lesser ‘total dose’ radiotherapy group seems to favor that mode of treatment.

Comparative Effectiveness of Three Different Radiotherapy Schedules in Women who have Undergone Surgery for Early Breast Cancer 50

It is common practice for women who have undergone surgery for early stage breast cancer to undergo radiotherapy. This is done to reduce the risk of cancer coming back in the breast.

This trial explores the comparative effects of two different radiotherapy schedules in women who have undergone surgery to remove early stage breast cancer. The way in which radiotherapy is given; number of doses, quantity of each dose, is known as ‘radiotherapy schedule’. A radiotherapy dose is measured in units called ‘grays’.

A total of 2236 women who had undergone breast cancer surgery were enrolled in the trial and divided into 3 treatment groups, with each group containing about 750 women.

Treatment schedules of radiotherapy given to women in each group was as follows:

  • Group 1 : 5 times a week, with a total dose of 50 gray in 25 doses of 2 gray
  • Group 2 : 5 times a fortnight, with a total dose of 41.6 gray in 13 doses of 3.2 gray
  • Group 3 : 5 times a fortnight, with a total dose of 39 gray in 13 doses of 3 gray

After a period of 5 years, when the researchers looked at how many women had a recurrence of cancer (cancer had come back), they found that this percentage was low in all three groups, ranging from 3.5% to 5.2%.

For about half of the women participating in the trial, photographs of their breasts were taken before and after treatment. On comparing these photographs, researchers found that about 1/3rd of these women had changes in the appearance of their breast, but most of the changes were described by the women themselves as ‘mild’. 40% of the trial participants (all groups combined) reported changes in the appearance of the breast or breast hardness. Women in group 3 had slightly fewer changes than women in the other groups.

Pain in the arm and shoulder was experienced by nearly 1/3rd of the total participants with more women from Group 1 reporting it than the other two groups. However, this difference was too small to be important.

After 10 years, these women were followed up once more and similar results emerged with Group 3 women having fewer adverse changes to the breast compared to other two groups. Researchers also found that the number of women whose cancer had come back in the breast remained low at 10 years and was similar in all 3 groups.

The researchers concluded that all three treatment schedules were equally effective in improving quality of life and disease free survival among women who had undergone breast cancer surgery.

How well does Nonparticle Albumin Bound (NAB) Paclitaxel work when given in Combination with Gemcitabine to Women Suffering from Metastatic Breast Cancer? 51

Nonparticle Albumin Bound (NAB) Paclitaxel and Gemcitabine are both commonly used, effective chemotherapy drugs used in treatment of breast cancer. Both these drugs work in different ways to stop growth and spread of cancer. Keeping this in mind, in this trial, researchers wanted to find out how well these two drugs worked in combination in improving prognosis among women who has metastatic breast cancer.

This trial was done by Roy and his co-researchers in 2009 with support from Mayo Clinic National Cancer Institute (NCI).

50 women with metastatic breast cancer took part in the trial. They were given NAB-Paclitaxel (125 mg/m2) and Gemcitabine (1000 mg/m2) on day 1 and day 8 of a 21 day cycle of treatment. This treatment was continued till patients showed disease progression.

The impact of the treatment was assessed by seeing how many women gave Confirmed Tumor Response i.e. substantial reduction in the cancer. The average progression free survival (duration for which patient lived without any increase in cancer) was also calculated.

NAB Paclitaxel treatment results in metastatic breast cancer patients

Half of the women enrolled in the trial showed Confirmed Tumor Response.

The median progression free survival among these women was 7.9 months. This means that half of the women lived without worsening of disease for at least 7.9 months. The shortest time for which a woman of this group lived free from disease progression was 5.4 months while some were able to remain progression free for as long as 10 months.

At 6 months, researchers wanted to see how many women had progression free survival and how many had overall survival (i.e. survival with or without progression).

NAB Paclitaxel treatment results in metastatic breast cancer patients

At 6 months, 60% of the women who took the treatment were surviving, without any increase in their cancer while total survival rate (with or without increase in cancer) was more than 90% among the trial participants.

Side effects experienced by the trial participants were also studied. Most commonly felt side effects were neutropenia (decrease in number of white blood cells in the body), fatigue (tiredness), anaemia (decrease in hemoglobin levels), Dyspnea (difficulty in breathing) and Thrombocytopenia (decrease in blood platelets). Researchers observed that the treatment was well tolerated with only few participants showing serious side effects.

Combining NAB-Paclitaxel and Gemcitabine gives good treatment response among metastatic breast cancer patients. More research is needed on this to be sure of this.

Clinical Trial Checking effectiveness of Zoledronic Acid in reducing pain Caused by Breast Cancer which has spread to the bones 52

In some breast cancer patients, the cancer spreads to the bones and affects the patients’ quality of life due to frequent and severe pain caused by it. In such cases, a pain-relieving drug known as Zoledronic acid can be used to reduce pain among patients, thus improving their quality of life. Zoledronic acid is also believed to stop other bone problems along with providing pain-relief in such patients.

Since Zoledronic acid is to be taken once every 3 weeks and takes 15 minutes for each dose to be given, it can easily be taken by patients at home, with no requirement to go to the hospital for it. In this trial, Professor A Howell and Dr. A Wardley, with assistance from Novartis compare the effect of having Zoledronic acid at home versus having it at the hospital.

The effect of this treatment on the patients’ quality of life was also looked at. Overall safety and tolerability of the drug (if are patients able to take it without any major problems) was also seen along with the pain relieving action of the drug. Researchers knew that Zoledronic acid can affect the kidneys so kidney function of participants was checked regularly during treatment period to ensure no kidney damage.

A total of 100 breast cancer patients whose cancer had spread to their bones and who were undergoing hormone therapy were enrolled in the trial. All these women were given the first 3 doses of Zoledronic acid in the hospital. The next 3 doses were given either at home or at the hospital and for last 3 treatments, those who had the second round of treatment at home were given last 3 doses in the hospital and those who took it in hospital were given last 3 doses at home.

Researchers observed that:

  • Treatment with Zoledronic acid was effective in reducing pain among the participants
  • Pain relief was greater when treatment was given at home.
  • Improvement in physical and social quality of life was higher when treated at home.
  • No kidney damage was found in any of the women in the trial.

Researchers concluded that Zoledronic acid, particularly when used at home, was safe, tolerable and effective in reducing pain among women whose breast cancer had spread to the bones.

 

Is Sentinel Lymph Node Biopsy better than Standard Treatment of the armpit in Breast Cancer? 53

When a patient is diagnosed with breast cancer, before or during surgery, doctors check the lymph nodes under the arm to see if they contain cancer cells. This is done to detect presence (if any) of cancer cells in the lymph nodes which can then be removed during the same or a second operation.

It is commonly done by removing some or all the lymph nodes from the patient’s armpit and then observing them under the microscope. This is the standard treatment (most commonly used treatment). However, removing the lymph nodes may cause swelling of the arm due to gathering of fluid in the area.

An alternative way which is used by doctors to check the lymph nodes for presence of cancer cells is the Sentinel Lymph Node Biopsy. In this, doctors only check the first node in the armpit into which lymph fluid enters from the breast. If this node does not have cancer cells, it is very unlikely that cancer cells are present in the other lymph nodes.

Professor Robert Mansel conducted a trial with support from National Institute for Health Research Cancer Research Network (NCRN) and The Research and Development Office of Wales (NHS) to see if Sentinel Lymph Node Biopsy was better than standard treatment in terms of fewer side effects and improved quality of life after surgery for early breast cancer.

The trial was carried out on 1031 patients who had been diagnosed with breast cancer and whose lymph nodes needed to be checked for presence cancer cells. They were divided into 2 equal groups:

  • Group 1 had Sentinel Lymph Node Biopsy
  • Group 2 had Standard Treatment

The trial enrolled patients from 1999 to 2004 and results collected from patients in 2006 showed that more Group 2 patients suffered more side effects than Group 1. Side effects included:

  • Loss of sensation in arm.
  • Reduced shoulder movement

People who had Sentinel Lymph Node Biopsy (Group 2) rated their quality of life higher than those in Group 1.

Sentinel Lymph Node Biopsy is better than standard treatment in terms of lesser side effects and better quality of life after surgery.

Comparing the effectiveness of Chemotherapy and Radiotherapy when given sequentially (one after the other) or in synchronization (together) in women who have undergone surgery for early stage Breast Cancer. 54

Radiotherapy and Chemotherapy are often used, alone or in combination after breast cancer surgery to prevent cancer recurrence (cancer coming back). In this trial Dr Fernando, supported by Cancer Research UK and the National Institute for Health Research Cancer

Research Network (NCRN) conducted a trial to see if giving chemotherapy followed by radiotherapy was as effective as giving the two in synchronization (together). The researchers also noted the side effects of both treatment methods.

The researchers enrolled 2296 women with early stage breast cancer who had undergone breast cancer surgery. They were put in 2 treatment groups:

  • Group 1 had 1146 participants who were given Sequential treatment i.e. radiotherapy after chemotherapy
  • Group 2 had 1150 participants who were given Synchronous treatment i.e. radiotherapy between 2 cycles of chemotherapy.

After 5 years, the researchers then observed how many participants had local recurrence of cancer (cancer had come back in same area i.e. breast).

radiotherapy and chemotherapy for breast cancer given sequentially and synchronously

Cancer had come back in more women from the group which was given Sequential treatment compared to the group which was given Synchronous treatment (ref: Graph).

Side effects such as sore skin were more commonly seen in women who were given Synchronous treatment. However, self-reported quality of life was similar in both groups.

The research team concluded that having radiotherapy and chemotherapy at the same time (Synchronous treatment) helps prevent re-occurrence of cancer better than giving these treatments one after the other (Sequential treatment).

Comparing the treatment response for Ixabepilone and Capecitabine versus Capecitabine alone in women with Metastatic Breast Cancer in whom Anthracycline and Taxane drug treatments have been ineffective. 55

Anthracycline and Taxane are two classes or types of drugs commonly used in treatment of breast cancer. However, in some cases, the breast cancer may be resistant to these drugs and would therefore continue to spread in spite of being treated with these drugs. In such cases, other anti-cancer drugs may prove effective.

Thomas and his co-researchers took up a clinical trial in 2007 to check if 2 other FDA approved anti-cancer drugs called Ixabepilone and Capecitabine could succeed in treating these women’s cancer where Anthracyclines and Taxanes had failed.

The trial was aimed at seeing the treatment response of these two different chemotherapy drugs when used in combination (Ixabepilone + Capecitabine) compared to Capecitabine alone.

A total of 752 such women were enrolled in the clinical trial and divided randomly into 2 treatment groups. Neither the researcher nor the women participating in the trial could decide which group they would be put into. This is known as randomization which is used in such trials to avoid bias on part of both researchers and participants and thus ensure accurate, reliable results.

  • Group 1 had 375 participants who were given Ixabepilone 40 mg/m2 intravenously on day 1 of a 21-day cycle and Capecitabine 2,000 mg/m2 orally on days 1 through 14 of a 21-day cycle\
  • Group 2 had 377 participants who were given Capecitabine alone 2,500 mg/m2 orally on days 1 through 14 of a 21-day cycl

The graphs shown below compare the treatment response of both groups in terms of:

  • Progression Free Survival (duration for which patient survives without increase in cancer)
  • Overall Survival (duration for which patient survives)
  • Overall Response Rate (Proportion of Participants who Responded to Treatment i.e. showed improvement in cancer after treatment)
  • Duration of Response (duration for which the participants responded to treatment).

Ixabepilone-Capecitabine-metastatic-breast-cancer-treatment

Group 1 participants responded for more duration to the treatment given to them (Ixabepilone + Capecitabine) and also survived longer.

While half of the women in Group 1 responded to treatment for a minimum of 6.4 months, this duration was lesser (5.6 months) for women in the other group.

The median duration of PFS for Group 1 was 5.8 months which tells us that half the women of this group could survive without any increase in disease for at least 5.8 months. This was lower in case of group 2 (4.2 months).

Similarly, overall survival and duration for which the patients responded to treatment was also more in the first group.

In Group 1, 50% of women survived for 12.9 weeks or more while in the second group 50 % lived for at least 11.1 weeks.

Ixabepilone-Capecitabine-metastatic-breast-cancer-treatment-1 Ixabepilone-Capecitabine-metastatic-breast-cancer-treatment-2

Additionally, more Group 1 participant gave positive and faster response to treatment than those in Group 2 (ref: above Graphs).

Serious side effects of treatment such as neuropathy (damage to nerves), neutropenia (decrease in number of white blood cells in the body) and fatigue (tiredness) were found to be more common in Group 1. Treatment related safety aspects were also studied.

Ixabepilone-Capecitabine-metastatic-breast-cancer-treatment-3

Though treatment related side effects, adverse health events and rate of discontinuation from trial was higher for Group 1, this Group also had a lower death rate compared to Group 2 (ref: Graph above).\

All this evidence points that the combination of Ixabepilone + Capecitabine works better (but with increased side effects) than Capecitabine alone in treating women with metastatic breast cancer who have been previously unsuccessfully treated with Anthracycline and Taxane drugs.

Is exercise beneficial for women undergoing treatment for Early Stage Breast Cancer? 56

According to a small study conducted on few early stage breast cancer patients, exercise is helpful in improving the quality of life and reduce feelings of fatigue, anxiety and depression among them. However, a larger trial, involving more participants was required to confirm this belief.

Keeping this in mind, with support from Cancer Research UK, Professor Nanette Mutrie did a clinical trial on 203 early stage breast cancer patients to assess the benefits if any, of exercise as a therapy for improving these patients’ quality of life.

The participants of the trial were randomly placed in two groups:

  1. Group 1 had 101 participants who did exercise
  2. Group 2 had 102 participants who did not exercise

Group 1 participated in a 45 minute supervised group exercise session twice a week and were encouraged to exercise once a week at home in addition to these group sessions. Group 2 did not do any exercise.

The research team assessed both the groups in terms of:

  • Body mass index (BMI)
  • Fitness levels and shoulder mobility
  • Quality of life
  • Mood
  • Fatigue

These assessments were made 3 times: once at the beginning of the trial, then at 12 weeks and again at 6 months from the date when trial was started.

Those in the exercise group performed better in many but not all aspects that were measured during the trial. At the second evaluation (at 12 weeks), there was an improvement in the fitness levels, shoulder mobility and mood of the participants in exercise group. This improvement was sustained at the 3rd evaluation (at 6 months) accompanied by reduction in fatigue and hormonal symptoms.

Exercise provided a functional and psychological benefit to the patients of this trial and researchers strongly recommend exercise as a therapy for improving the quality of life in early stage breast cancer patients.

Effects of different exercise regimens in women who have finished Breast Cancer treatment 1-3 years ago? 57

It is known that exercise, in general helps in improving a person’s quality of life and overall wellbeing. In this trial, the researcher (Dr Amanda Daley) wanted to see if exercise could help in improving the quality of life and well-being of women who have completed treatment for breast cancer 1 – 3 years ago. This trial was conducted in collaboration with Cancer Research UK.

108 women who had completed their breast cancer treatment between 1 and 3 years back were enrolled in the trial and divided into 3 groups:

  • Group 1 had 36 participants who were made to do aerobic exercise i.e. the kind of exercise which increases the heart rate. An exercise therapist and counselor guided, encouraged and helped the participants in developing a positive outlook towards exercise.
  • Group 2 had 36 patients who followed a ‘body conditioning’ programme i.e. the kind of exercise which increases the flexibility, balance and posture of the body. This group had an exercise therapist but no exercise counselor.
  • Group 3 had 36 participants who were under ‘usual care’ i.e. they were not made to do any kind of exercise.

The third group provided a baseline against which the other two groups could be compared i.e. effect of some type of exercise (Group 1 & 2) versus no exercise (Group 3) comparison.

After 8 weeks of the start of trial, the participants were asked to fill a questionnaire which had questions which assessed the participants’ quality of life. The answers were analyzed and it was seen that Group 1 (aerobic exercise group) reported better quality of life compared to other two groups.

There was at least a short term improvement in quality of life among women who were treated for breast cancer 1-3 years ago.

Is Cognitive Behavior Therapy Useful in Treating Insomnia among Cancer Patients? 58

Insomnia or sleeplessness, is a sleep disorder in which there is an inability to fall asleep or to stay asleep as long as desired. This disorder is commonly seen in people suffering from cancer. The reason for this could be stress of the disease or side effects of the medications taken for curing cancer.

If left untreated, insomnia may cause the patient to become depressed and more anxious in turn, making it more difficult for them to cope with their condition (cancer). This disturbance could also lead the patients to feel worse, physically as well as mentally.

The problem of sleeplessness is generally treated by doctors with sleeping pills or similar other drugs. However, in this trial, Professor Colin Espie, with support from Cancer Research UK tried a new way of treating insomnia, other than medicine among cancer patients.

The new method was CBT (Cognitive Behavior Therapy). The aim of the trial was to see which method: CBT or the usual treatments which have been given over the years (sleeping pills etc.) was better in relieving sleeplessness among cancer patients.

150 cancer patients took part in this trial. They were put into 2 groups as follows:

  • Group 1 had 100 participants who had 5 sessions of CBT with a trained therapist
  • Group 2 had 50 participants who had the usual treatment for insomnia

The participants were asked to maintain a sleep diary in which they were asked to note down details of their sleep pattern. Aspects related to quality of life in these participants such as: tiredness, anxiety and depression were also studied. Highlights of the trial results are below:

  • Participants who underwent CBT sessions slept for about an hour longer each night than participants who got usual treatment.
  • The CBT group reported fewer problems like tiredness, anxiety and depression compared to usual treatment group.
  • None of the groups reported any side effects of the treatments.

Cognitive Behavior Therapy may be useful and acceptable for treating insomnia among cancer patients.

Clinical Trial Comparing Treatment Benefit of Paclitaxel followed by FEC regimen versus Paclitaxel and RAD001 followed by FEC in Stage 2 & Stage 3 Breast Cancer Patients 59

M.D. Anderson Cancer Center conducted a clinical trial in 2013 in collaboration with Novartis to find out which of the following treatment combinations were more effective in stage 2 and 3 breast cancer patients who were not positive to ER, PR or HER2 receptors:

  • Treatment 1: Paclitaxel followed by FEC (Fluorouracil + Epirubicin + Cyclophosphamide)
  • Treatment 2: Paclitaxel + RAD001 followed by FEC (Fluorouracil + Epirubicin + Cyclophosphamide)

RAD001 is an mTOR inhibitor that is known to sensitizes tumor cells to the cytotoxic effect of carboplatin. Researchers were interested in studying its effects with this treatment regimen.

50 women suffering from breast cancer were enrolled in the trial and randomly divided into 2 treatment groups. Neither the researchers nor participants of the trial could decide which group they would be put into.

  1. Group 1 had 27 participants who were given Treatment 1.
  2. Group 2 had 23 participants who were given Treatment 2.

Treatment response given by participants of both groups was measured in terms of:

  • Complete Response – disappearance of cancer
  • Partial Response – significant reduction in cancer
  • Stable Disease – no change (increase or decrease) in cancer
  • Progressive Disease – increase in cancer

Paclitaxel followed by FEC for breast cancer

As can be seen in the above Graph, treatment response of Group 1 improved with time. More of these women had complete response and partial response at 24 weeks compared to 12 weeks. Also, at the end of 24 weeks, none of them showed increase in their cancer compared to 11.2% who showed cancer growth at 12 weeks.

Paclitaxel followed by FEC and RAD001

In this trial Group 1 gave better treatment response compared to Group 2. Group 2 seemed to give partial response quickly, but in the long run – Group 1 indicated better prognosis.

Out of the two treatment regimens tried in this study, combination of Paclitaxel and FEC seems more effective in improving prognosis of breast cancer patients in this limited clinical trial study.

Is MRI helpful in providing more information compared to that provided by Ultrasounds, Mammograms, Fine Needle Aspirates and Needle Biopsies in patients about to undergo Breast Cancer surgery? 60

The most commonly used diagnostic procedures for detecting breast cancer include Breast Ultrasounds, Mammograms, Fine Needle Aspirates or Needle Biopsies. However, in some cases these tests are unable to tell how widespread the cancer is before the surgery. Because of this, a second operation may become necessary.

With this in mind, researchers thought of finding out if MRI (Magnetic Resonance Imaging) was better at diagnosing the full extent of cancer in women before surgery. If this was so, it would help prevent a second operation because, with prior knowledge of all affected areas of the breast, doctors could target all of them during the first operation itself.

Thus, in this trial, the researcher, Professor Lindsay Turnbull, in collaboration with Hull and East Yorkshire NHS Trust, NIHR Health Technology Assessment (HTA) programme and the National Institute for Health Research Cancer Research Network (NCRN) conducted a clinical trial on women who were scheduled to undergo breast cancer surgery wherein they compared the results of MRI with standard diagnostic techniques.

1623 women with breast cancer were included in the trial. All of them had a standard mammogram and breast ultrasound. Additionally, half of them had an MRI and the other half did not have it.

On checking if there was a difference in the number of women in both these groups who required a second operation, researchers found that there was no such difference.

Having an MRI made no difference in the number of women requiring a second operation i.e. it provided no additional diagnostic benefit above the standard diagnostic procedures which are currently being used. Considering this, the extra cost incurred for doing an MRI seems unnecessary.

Is High-Dose Toremifene Helpful in Treating Women with Fulvestrant Resistant Metastatic Breast Cancer? 61

In women who have Hormone Receptor Positive and metastatic breast cancer, doctors often use a group of drugs called ‘Aromatase Inhibitors’ as first treatment after which a drug called Fulvestrant is generally given. However, this treatment combination might not be effective in controlling the cancer in all women. Some women develop resistance.

Keeping this in mind, this trial was conducted by Mori and Nagao in 2014 to check the effectiveness of another FDA (Food and Drug Administration) approved drug called Toremifene in such women.

Two women with hormone receptor positive metastatic breast cancer were studied. They had developed two liver tumors each as a result of the spreading of breast cancer. The change in the size of their tumor was measured at start of treatment with aromatase inhibitor + Fulvestrant, after treatment, after 6 months of the treatment and then after treatment with high dose Toremifene.

Results are depicted in the graphs below –

Toremifene tumor response

 

In the case of the first woman who was 73 years old and had 2 tumors of size 23 mm and 25 mm initially, the first tumor remained same (23 mm) after treatment with Aromatase inhibitor and Fulvestrant therapy, grew after 6 months (36 mm) but shrunk a lot after the patient was given high-dose Toremifene (26 mm).

The second tumor shrank from 25 mm to 22 mm after aromatase inhibitor + Fulvestrant, grew back to initial size after 6 months (25 mm) and shrank a little when high dose Toremifene was given (24 mm).

Toremifene tumor response

The second woman who was enrolled in the study was 81 years old and had 2 tumors in liver (20 mm and 11 mm) at the start of treatment. The first one reduced to 13 mm after treatment with aromatase inhibitor + Fulvestrant but grew a little after 6 months (14). However, on being given high dose Toremifene, there was shrinkage (12 mm) in the tumor.

The second tumor showed a little growth (11 mm to 13 mm) after being given aromatase inhibitor + Fulvestrant. This growth continued and at 6 months, the tumor was 18 mm. High dose Toremifene was successful in reducing the size of this tumor to 14 mm which was higher than initial size but a reduction from 18 mm (most recent tumor measurement).

This was a limited study. Toremifene seems effective in improving prognosis in these women who have been previously unsuccessfully treated with multiple hormone therapies.

Is yearly Breast Cancer screening in middle-aged women with a family history of Breast Cancer Beneficial? 62

Women who have a family history of breast cancer (a close relative with breast cancer) are at an increased risk of developing breast cancer. In this trial, the researchers wanted to find out if yearly screening for breast cancer (checking for presence of breast cancer) in women who had family history helped in early identification and thus, better prognosis and improved chances of survival.

This trial, conducted by Dr James Mackay, with support from the National Institute for Health Research Cancer Research Network (NCRN) and the UK NHS Health Technology Assessment included 6701 women (40-49 years of age) with a family history of breast cancer. They all were made to undergo mammogram every year. Mammogram is a diagnostic procedure for identifying breast cancer.

benefits of yearly mamogram

A total of 136 women were diagnosed to have breast cancer. Out of these, most cases (77.2%) were diagnosed with the help of the mammograms while the remaining 22.8% were identified because of development of symptoms in them between the mammogram sessions (ref: Graph above).

The researchers also compared the results of their trial to 2 other similar trials (UK Age Trial and Dutch Trial) which were previously conducted on women for breast cancer diagnosis. They found that, by comparison, their own trial diagnosed cancers which were:

  • Smaller
  • Less likely to have spread to lymph nodes
  • More likely to be slower growing cancer i.e. lower grade cancers

Also, a prediction of 10 year survival was also made for participants of all 3 trials.

yearly mamogram improves life expectancy

As shown in the above graph, the chance of survival at 10 years after diagnosis were good in all three trials but comparative analysis showed much better chances for patients of the present trial compared to the other two.

The researchers calculated that 1 life could be saved for every 5000 mammograms done. Yearly mammograms for women with a family history of breast cancer can help save lives by early detection.

Effectiveness of Megestrol Acetate in postmenopausal women with Advanced Breast Cancer who have been previously unsuccessfully treated with Aromatase Inhibitor drugs 63

Hormone positive receptor, advanced breast cancer is commonly treated using aromatase inhibitor drugs (a class of drugs). However, in some cases, aromatase inhibitor drugs may fail in controlling the growth and spread of cancer.

In order to find a possible solution to this, Bines and co-researchers in 2014 conducted a trial to see if an anticancer drug called Megestrol Acetate could be effective and well tolerated by women with this type of cancer who have been previously unsuccessfully treated with aromatase inhibitor drugs.

48 such women joined this clinical trial. Treatment Response among them was measured by:

  • Clinical Benefit Rate – percentage of women who had disappearance/reduction in cancer or stability of disease (no increase or decrease)
  • Duration of Clinical Benefit
  • Progression Free Survival – duration for which the patients survived without any increase in their cancer

Megestrol-treatment-results-2 Treatment results using Megestrol in advanced breast cancer patients

The graph above shows that good treatment response was seen in several women who participated in the trial (40%).

Treatment results using Megestrol in advanced breast cancer patients

 

As shown in the above graph, the median duration of clinical benefit was 10 months. This can be understood as follows: half of the women in this group got clinical benefit of treatment for 10 month or longer. The least time for which a woman of this group benefitted was 8 months while some continued to get positive health benefits for 14.2 months.

Similarly, progression free survival (PFS) was also calculated for the women. 50% of these women lived without worsening of disease till at least 3.9 months. Some continued to live so till 4.8 months while the lowest duration of PFS was 3 months.

Megestrol side effects

The graph above shows the various side effects experienced by the trial participants. Overall, few of them suffered serious side effects of treatment.

Researchers conclude that Megestrol Acetate has good anticancer activity with acceptable side effects, making it a good, cost-effective treatment option.


Does adding Trastuzumab to a treatment regimen of Docetaxel and Doxorubicin improve prognosis in Metastatic Breast Cancer patients? 64

The National Cancer Institute (NCI) conducted a clinical trial in 2012 on 84 women who were suffering from metastatic breast cancer to compare the benefits of using combination chemotherapy of Docetaxel and Doxorubicin with and without Trastuzumab.

These women were put into two different treatment groups.

  1. Group 1 had 38 women who were given Docetaxel + Doxorubicin
  2. Group 2 had 46 women who were given Docetaxel + Doxorubicin + Trastuzumab

Treatment response given by participants of both groups was measured in terms of:

  • Complete Response – disappearance of cancer
  • Partial Response – significant reduction in cancer
  • Stable Disease – no change (increase or decrease) in cancer
  • Progressive Disease – increase in cancer

Due to certain reasons, it was not possible to evaluate treatment response in some participants. These have been included as “not evaluable”.

Trastuzumab-combination-therapy-1

 

Trastuzumab-combination-therapy-2

Graphs above show the treatment response given by women in both groups at 4 weeks.

The tumor reduced or disappeared in nearly half of the women of Group 1 (47%) and Group 2 (46%). It remained stable (no increase or decrease) in 29% of Group 1 women and 24% women of Group 2. More women of Group 1 (25.8%) experienced disease aggravation than Group 2 (19.6%).

However, these results might not be give us the correct idea because some women in both groups were not evaluated due to certain reasons. This might affect the percentages mentioned here.

Trastuzumab-combination-therapy-3

 

Progression Free Survival i.e. PFS (duration for which person lives without any increase in cancer) was almost same for both groups but looking at overall survival (duration for which patient lives with or without growth in cancer), it was clear that Group 2 survived much longer than Group 1.

The median duration of PFS for Group 1 was 11 months. This means that 50% of the women of this group lived for at least 11 months. The shortest time for which women of this group survived without increase in disease was 8.6 months while some had PFS even up to 12.8 months.

The median duration of PFS for Group 2 was 10.6 months, almost as long as Group 1. Lowest and highest PFS were 5.6 months and 15.7 months.

50% of the women of the first group lived for 24.6 months, with or without worsening of disease. Minimum OS (Overall Survival) was 14.7 months and highest was 37.3 months. Group 2 had much higher median duration of OS (31.8 months) than Group 1. Lowest (23.7 months) and highest (44.9 months) duration of OS were also much longer for this group.

While treatment was almost equally effective in both groups for short term (4 weeks) benefit and progression free survival, the overall survival was more in the second group.

Is acupuncture effective in reducing fatigue in women who have undergone Breast Cancer treatment? 65

It is known from past research that a large number of the women who undergo treatment for breast cancer experience some or a lot of fatigue (tiredness). This may go on for years after completion of treatment. In such cases, it leads to a compromised quality of life and can have a negative impact on daily activities.

This trial aims to find out if acupuncture treatment can help in reducing fatigue levels in such women. Acupuncture is a type of alternative therapy which uses fine needles which are inserted in the skin at particular spots in the body.

Professor Alexander Molassiotis did this trial with help from Breakthrough Breast Cancer, King’s College London, National Institute for Health Research Cancer Research Network (NCRN), The Christie NHS Foundation Trust, The Royal Marsden NHS Foundation Trust and the University of Manchester.

302 women who had already completed their breast cancer treatment were made a part of this trial. They were randomly put into two treatment groups. Neither the researcher nor patients decided which group they (participants) would be put into.

  • Group 1 had 227 women who were given acupuncture once a week for total 6 weeks
  • Group 2 had 75 women who were given the usual care given after treatment. Additionally, they were also given information on how to cope with fatigue.

All the participants (302) were asked to fill in a questionnaire at the beginning of the trial and once again at the end of 6 weeks. The questions were about the level of fatigue experienced by the participants and their general health and wellbeing.

Completed questionnaires could be collected from 246 participants at the end of the trial. Out of these, 181 were from Group 1 and 65 were from Group 2.

An analysis of the answers given by each participant in the questionnaire was done. According to it, Group 1 participants were less tired than the second group.

Acupuncture seems to be a potentially beneficial therapy for reducing fatigue in women who have had breast cancer treatment.

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