Tag Archives: HER2

Herceptin and HER2 Positive Breast Cancer – Is It Effective – Part Two

Image Source: rgbstock.com / Jana Koll
Image Source: rgbstock.com / Jana Koll

Herceptin and HER2 Positive Breast Cancer – Is It Effective – Part Two

Because I like to keep you updated with the latest information and research, this post is a follow up to my post “Herceptin and HER2 + Breast Cancer – Is It Effective?” dated 2/18/2014.  Since writing that post, I have read some newer research and I wanted to share this with you.

A Synopsis Of My Last Post…

In my February 2014 post I  referred to one study done in 2002 1 in which 114 women, all of whom had metastases to other parts of their bodies, were given only Herceptin to treat their HER2 positive breast cancer.  The researchers reported that seventeen (57%) out of thirty patients had an objective response (which means either a partial or complete response) and twenty-two (51%) out of forty-three patients had what was termed a clinical benefit, an informal term which generally means anything other than progression of disease.  These patients also did not experience progression of disease at the follow-up appointment scheduled 12 months later.  Loosely translated, this means that roughly fifty percent of women with metastatic, HER2 positive breast cancer, treated only with Herceptin, remained alive after twelve months.

An Update Of The HERA Trial

The other article I referenced which appeared on the National Cancer Institute website 2 in 2011 discussed the Herceptin Adjuvant (HERA) trial, run by the Breast International Group beginning in 2001.  At the time of reporting the HERA trial was not complete.  We now have the final results of the HERA trial which was carried out for 8 years.

After finishing surgery, chemotherapy and/or radiotherapy, 5102 women with HER2 positive breast cancer were randomly assigned to one of three groups.  In the first group 1703 patients received trastuzumab (Herceptin) every 3 weeks for 1 year, a second group of 1701 patients were treated with Herceptin for 2 years, and in the third group 1698 patients were merely observed and given no Herceptin.  After the initial results of the study were released in 2005 the observation group was offered the chance to be moved into one of the two groups receiving Herceptin.

One of the reasons the HERA trial was conducted was to decide how long Herceptin should be given to achieve the best, disease free survival.  In terms of percentages, 75.8% of women who took Herceptin for two years were still alive, and 76% of women who took Herceptin for one year were still alive.  So taking the drug for an additional year conferred no extra benefits.  As a result of this study, most oncologists recommend that Herceptin be taken for one year.

The Latest Research

In my previous article about the efficacy of Herceptin I didn’t give a very glowing report and indeed, the statistics weren’t all that impressive, at least not to my eyes.

Unfortunately we don’t have any research indicating what a good healthy diet and specific supplements would do for women with HER2 positive breast cancer, no one will be funding THAT study.

In the meantime I have had some newer research put in front of me by an interested reader, which study was reported in the New England Journal of Medicine earlier this year.   This research study followed 406 node-negative (meaning cancer had not spread to their lymph nodes) women with stage 1, HER2 positive breast cancer. These women had tumors up to 3 cm in size and were treated with a combination of paclitaxel (Taxol) and Herceptin weekly for 12 weeks, followed by 9 months of Herceptin alone.  The 3 year survival rate was 98.7%, a much more impressive figure.

To see the full results of the trial, check out “Clinical practice-changing trials: the HERA study paradigm”4 below.  It’s a downloadable PDF file.  See especially Table 1 Efficacy Results Of The Herceptin Adjuvant Study With Different Follow-Up Times, page 3 of that document.  You can draw your own conclusions.

Word Of Caution

I’d like to insert a couple of things here, just a tiny word of precaution.  Take into account, please, that the research was supported by Genentech, the company that stands to gain the most by the research.  Also please note that in the 2015 research the women who took part in the study were considered stage 1, their tumors were small and the disease had not spread elsewhere in the body.  These are the women who have the best chance of survival anyway, their disease being caught early.

Another thing to consider is that both Taxol and Herceptin can be very hard on the heart.   Nine patients (true, a relatively small percentage, only 0.54%, but if you’re one of those women…) in the HERA trial who received Herceptin developed severe congestive heart failure.  Even the researchers in the 2015 study 3 stated “the decision to use trastuzumab and chemotherapy is influenced by the toxicity of the treatment regimen.”

This cardiotoxicity may or may not be reversible.  If you are considering going on this drug, it might be wise to consult a naturopath for correct dosages of cardio-protective supplements, such as CoQ10, garlic and grapeseed extract.

References:

1.  Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer – http://www.ncbi.nlm.nih.gov/pubmed/11821453

2.  Trastuzumab after Chemotherapy Is Effective in HER2-Positive Breast Cancer – http://www.cancer.gov/types/breast/research/trastuzumab-after-chemo

3.  Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer – http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313867/

4.  Clinical practice-changing trials: the HERA study paradigm — http://www.researchgate.net/profile/Dimitrios_Zardavas2/publication/258057600_Clinical_practice-changing_trials_the_HERA_study_paradigm/links/53d64f740cf2a7fbb2ea9b1b.pdf

For some good dietary tips for HER2 positive breast cancer, see my article The Best Diet For HER2 Positive Breast Cancer.

GET MY BEST TIPS on getting through breast cancer and preventing recurrences by signing up for my free e-newsletters and e-books on the right.  You can also “like” me on Facebook (MarnieClark.com) to get my inspirational snippets, news and updates.  I promise to do my utmost to keep you informed and empowered on your healing journey… and beyond.  

The Best Diet For HER2 Positive Breast Cancer

Image source: rgbstock / AI71 Image source: rgbstock / AI71

The Best Diet For HER2 Positive Breast Cancer

Continuing my series of articles on dietary recommendations for particular types of breast cancer, this one is for those of you who have been diagnosed with HER2 Positive (HER2+) breast cancer.

What Exactly is HER2 Positive Breast Cancer?

HER2 positive refers to a type of breast cancer that overexpresses the HER2/neu gene. About 15-20% of breast cancers are HER2+, meaning the cancer is fueled by over-production of the human epidermal growth factor receptor 2 protein.  HER2+ breast cancers contain excess copies of this gene, leading to dramatically more HER2 protein on the surface of cancer cells.  Because of this protein, which produces signals that tell the cells to grow, they do so out of control, causing this form of breast cancer.

Many women are told that a HER2+ diagnosis is associated with a significantly higher chance of local breast cancer recurrence (that means the cancer often returns in the same breast as the original tumor). Before the late 1990s, women with HER2+ breast cancer had poorer survival rates. Today, however, because of targeted therapies like Herceptin, this is no longer the case and it is a much more treatable disease.  Herceptin works by attaching to HER2 receptors on cancer cells, blocking signals that cause growth, and alerting the immune system to destroy the cancer.

Can Diet Make A Difference?

Please know that there are plenty of things you can eat and supplements you can take which will make a big difference for you and will assist your return to wellness.

Research shows that there are some foods and spices that are especially potent in inhibiting HER2+ breast cancer cell growth and proliferation and in promoting the process known as apoptosis (programmed cell death).  In addition, some foods have been found to amplify the effects of Herceptin.

Food That You Should Include In Your Diet If You Have HER2+ Breast Cancer

Wherever possible, try to ensure that the items from the list below are organic, because if you are trying to heal from cancer you need to stay away from conventionally grown produce and meats as much as possible due to the pesticide and herbicide residues.  You really need to keep the toxin load at a minimum to give your body a better chance to heal.

Here’s the list of foods and spices (or their components) which have been found to inhibit the growth or proliferation of HER2+ breast cancer cells. Many of these things also help to counteract the toxicity of Herceptin:

bell peppers (capsicum), black pepper, blueberries, red cabbage, green cabbage, cauliflower, bok choy/Chinese cabbage, broccoli, brown rice, Brussels sprouts, purple carrots, cherries (particularly sour cherries), celery, cranberries, red grapes, green tea, horseradish, herring, hot peppers, lake trout, mackerel, mustard and mustard greens, extra virgin olive oil, red onions, parsley, pomegranates, raspberries, black rice, wild caught salmon, sardines, tomatoes, turmeric, turnips and turnip greens, walnuts, watercress. See also my article Study Shows Curcumin Works as Well as Herceptin In Some Cases.

This is not an exhaustive list – indeed, there are many other foods which are known to have anti-cancer benefits – but this is the list that we have research for which indicates a potent anti-HER2+ activity. See my page Diet and Cancer for a list of other foods that have anti-cancer activity.

I recommend that breast cancer patients and survivors with HER2+ breast cancer include as many of the things on the “good” list above and limit or avoid the “please avoid” things that appear below.

Please Avoid These

No food list is complete without mentioning the things that should be avoided for HER2+ breast cancer because they have been shown to promote HER2+ breast cancer growth or increase HER2+ expression. Those things are: alcohol, folic acid supplements, genistein supplements, grapefruit, the Chinese herb ligusticum chuanxiong, the Chinese herb Si-Wu-Tang (may interfere with the effectiveness of Herceptin), soy protein isolate, cigarette smoking.

Foods That Assist the Effects of Herceptin

The following foods have been found to assist the effects of Herceptin against HER2+ breast cancer:

açaí berries, blackberries, boysenberries, cherries (particularly sour or tart), blackcurrants, cruciferous vegetables (broccoli, cabbage, cauliflower, kale, Brussels sprouts etc), flaxseed, green tea, extra virgin olive oil, passion fruit, purple or red plums, pomegranates, black raspberries, black or purple rice, strawberries, purple sweet potatoes, walnuts

There are also quite a number of essential oils and other supplements which research has indicated are helpful against HER2 positive breast cancer so be sure to check out those resources on my website.

Thanks for some of the dietary recommendations in this article goes out to http://foodforbreastcancer.com/ – written by Sarah Charles, also a breast cancer survivor and a woman of sharp intellect, Sarah has a mathematics degree from UCLA and is a Harvard graduate.

GET MY BEST TIPS on getting through breast cancer and preventing recurrences by signing up for my free e-newsletters and e-books on the right.  You can also “like” me on Facebook (Marnie Clark, Breast Health Coach) to get my inspirational snippets, news and updates.  I promise to do my utmost to keep you informed and empowered on your healing journey… and beyond.  

Herceptin and HER2 + Breast Cancer – Is It Effective?

 

Artwork courtesy of rgbstock.com / ba1969
Image Source: rgbstock.com / ba1969

Herceptin and HER2 + Breast Cancer – Is It Effective?

I have had a couple of questions about HER2 positive (“HER2 +”) breast cancer and the drug known as Herceptin, or trastuzumab, and its effectiveness.  I did a bunch of research, here’s what I found out.

HER stands for human epidermal growth factor, and it is a protein that can affect the growth of some breast cancer cells.  It is actually found on the surface of healthy breast cells — in a healthy breast there will be approximately 20,000 HER2 receptors, but when the cells are creating too many copies of this protein, known as overexpression, which occurs in approximately 25% of patients, there can be over 2 million receptors and that’s important because overexpression of the HER2 protein, as well as amplification of the HER2 gene, have been associated with impaired prognosis in patients with both early and advanced breast cancer.

How HER2 + Breast Cancer Is Different

In the late 1990’s researchers and doctors, being faced with an aggressive form of breast cancer that did not respond as well to the usual chemotherapeutic drugs, observed that for some breast cancer patients, overexpression of a particular gene known as HER2 meant that that patient often had a more aggressive form of breast cancer.

The HER2 gene makes a protein which creates a receptor that sits on the outside of a cell.  HER2 receptors act like antennae on the surface of cells and they receive signals that stimulate the cell to grow and multiply.   Breast cancer cells with too many HER2 receptors receive too many growth signals and thus start growing and multiplying too quickly.  Left untreated, this form of breast cancer can progress rapidly.

How Herceptin Works

Herceptin is a monoclonal antibody, or MAB, made by Genentech BioOncology.  MABs are a type of biological therapy made in a laboratory.  Monoclonal just means all one type.  MABs are designed to recognize and attach to specific proteins on the surface of cells.  Each MAB recognizes one very particular protein, in this case, the HER2 receptor.

Once Herceptin attaches itself to the HER2 receptor on the outside surface of breast cancer cells, it blocks them from receiving growth signals and flags it for destruction by the immune system.  It also blocks HER2 signalling within the cell, thus slowing or stopping the growth of the breast cancer.   According to Genentech BioOncology, the drug can also increase the effectiveness of other chemotherapeutic agents and it is designed to be used in combination with other chemotherapeutic drugs.

Is Herceptin Effective?

That’s a good question.  I will share the results of two studies I found: Efficacy and Safety of Herceptin (Humanized Anti-HER2 Antibody) As A Single Agent In 222 Women With HER2 Overexpression Who Relapsed Following Chemotherapy For Metastatic Breast Cancer.  Click that link to view the full PDF article.  You can print it out and take it to your doctor to explain the medical jargon.  If I read this correctly, the women in the study had metastatic breast cancer (meaning the cancer had already moved to other parts of the body) and so the results won’t be as good as for patients whose disease was caught at an earlier stage.  In this study, “57% of the responding patients were known to be free of disease progression at 12 months or more of follow-up.”  You can draw your own conclusions from that.

The second article appeared on the National Cancer Institute website:  Trastuzumab after Chemotherapy Is Effective in HER2-Positive Breast Cancer which discusses the Herceptin Adjuvant (HERA) trial reported in Lancet Oncology on February 25, 2011.   In this Italian study, 1,703 women received one year of adjuvant therapy with Herceptin (trastuzumab) while another 1,698 women were placed in an observation group.  Four years later, 79% of women in the Herceptin group were disease-free, compared with 72%  in the observation group.

The Down Side

Am I crazy or is that only a difference of 7%?  Not exactly huge, is it?  Especially considering that a one year course of Herceptin treatment costs about $70,000 in the United States, and that it comes with a long list of side effects, which include flu-like symptoms such as fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cells, muscle pain and, in 5-30% of patients, heart damage, especially when combined with the chemo drug Adriamycin.

2015 Update: I have written a follow-up to this post:  Herceptin and HER2 Positive Breast Cancer – Is It Effective – Part Two.

References:

Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235:177-182.

http://www.breastcancer.org/treatment/targeted_therapies/herceptin/how_works

Cobleigh MA, Vogel CL, Tripathy NJ, et al. Efficacy and safety of Herceptin (humanized anti-HER2 antibody) as a single agent in 222 women with HER2 overexpression who relapsed following chemotherapy for metastatic breast cancer. Program and abstracts of the American Society of Clinical Oncology 34th Annual Meeting; May 16-19, 1998; Los Angeles, California. Abstract 376

If you would like my help with getting through breast cancer in an inspiring and ultra-healthy way, please sign up for my free e-newsletters and e-book on the right, and/or “like” me on Facebook (MarnieClark.com).  It is my honor and my goal to help you through this so that you emerge from breast cancer feeling better than before, thriving!

T-DM1 Approved For Her2 Breast Cancer

Photo courtesy of freedigitalphotos.net and antpkr
Photo courtesy of freedigitalphotos.net and antpkr

T-DM1 Approved For Her2 Breast Cancer
 
Further to my post of August 15, 2012, New Chemotherapy Drug for HER2 – Genentech’s T-DM1, I have an update for you.  The FDA has finally approved T-DM1, now known as the brand-name Kadcyla, for women with HER2+, metastatic breast cancer. The new therapy has been approved for use in patients who have already undergone unsuccessful treatment with a combination of trastuzumab (Herceptin) and a taxane. 
 
An Interesting Method of Delivery

Kadcyla is a conjugate – it combines the drug trastuzumab, better known by the brand name Herceptin, and a powerful chemotherapy drug called DM1.  The trastuzumab portion targets HER2+ cells, then the attached chemotherapeutic molecule – the DM1, which is too toxic to deliver directly into the patient’s bloodstream – is delivered and attacks the cancer cell.   T-DM1 has helped inspire a new generation of antibody + drug conjugates.

Study Results

FDA approval was based on a study known as EMILIA, in which patients with HER2+, metastatic breast cancer who had failed treatment with a combination of trastuzumab and taxane were randomized to ado-trastuzumab emtansine or conventional therapy with lapatinib and capecitabine (Xeloda).  The patients given ado-trastuzumab emtansine resulted in significant improvements in both progression-free survival (9.6 vs 6.4 months) and overall survival (30.9 vs 25.1 months). 

The Down-Side (Why Is There Always A Down-Side?)

This sounds like really great news, however, the drug is not without risk (what else is new?).  The FDA requires labeling on Kadcyla to warn of risks of liver toxicity, reductions in left ventricular ejection fraction for the heart, and death.  In addition, there is risk of severe birth defects, so a woman’s pregnancy status should be determined before starting treatment, the FDA said.  The most common side effects associated with the drug were nausea, fatigue, musculoskeletal pain, thrombocytopenia, elevated liver enzymes, headache, and constipation.

As if all of that weren’t enough, the drug will cost $9,800 a month, or about $94,000 for a 9.5-month course of therapy.  Let’s hope it can keep people alive.

References:

http://www.medpagetoday.com/HematologyOncology/BreastCancer/35052

http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=114&abstractID=98675

http://chicago2012.asco.org/ASCODailyNews/LBA1.aspx

I send my love to everyone taking this journey right now. If you would like my help with getting through breast cancer in an inspiring and ultra-healthy way, please sign up for my free e-newsletters on the right, or “like” me on Facebook (MarnieClark.com) and I’ll do my utmost to keep you informed and empowered on your healing journey… and beyond.

New Chemotherapy Drug for HER2+: Genentech’s T-DM1

In June of this year, the results of a new study were released by Duke Cancer Institute for a breast cancer drug known as T-DM1 which is made by Genentech, a unit of Roche, who sponsored the trial.

I didn’t write an article about it at the time because I wanted to do a little more research.

How T-DM1 Works

T-DM1 is designed for those who are HER2 positive, meaning that their tumors have high levels of a protein called HER2.

T-DM1 works a little differently than most chemotherapy drugs.  It consists of toxins that are linked to proteins called antibodies.  The antibodies latch onto cancer cells and deliver their toxic payload directly into the cancer cells.  This is termed an antibody-drug conjugate.

More specifically, to make T-DM1, trastuzumab, the T in the name, is attached to DM1, a toxin more potent than the typical chemotherapy drug.

The trastuzumab latches onto cells with the HER2 protein protruding from their surface and is taken inside the cells.  Once inside, the antibody degrades and sets the toxin free. Although the toxin is still connected to the linker, it is still able to kill the cells.

According to the research, by doing this, side effects are supposedly reduced.

Study Results

The T-DM1 trial involved 991 women with metastatic breast cancer whose cancer was getting worse despite previous treatment with the drug Herceptin (also a Genentech drug) and taxane.  Half of the women in the study got T-DM1 and the other half received two drugs that are now commonly used for such patients — Tykerb, also known as lapatinib, and Xeloda, also known as capecitabine.

According to the study results, T-DM1 delayed the worsening of disease by about three months.  For those who received T-DM1, the median time before the disease progressed was 9.6 months, compared with 6.4 months for those getting the two other drugs.

While it is too early to state that T-DM1 prolonged lives (because not enough time had elapsed since the beginning of the trial and the release of the results), researchers were pretty confident that it would be beneficial.

T-DM1 Side Effects

I have been active in several breast cancer forums and I know of a few women who have been on the T-DM1 trials.  Here’s what some of them have had to say about side effects of T-DM1:

  • Neutropenia – neutrophils are a class of white blood cells in your immune system and neutropenia means a low count of neutrophils
  • Significant aching and stiffness of muscle and joints, pain and cramping – worse in hands and feet
  • Mouth sores, dry mouth
  • Drippy nose, sometimes bloody
  • Liver enzyme elevation
  • Cardiomyopathy
  • Fatigue
  • Lung inflammation
  • Heavy periods (if not menopausal)

I thought you might like to know.  To me, that list of side effects sounds a whole lot like most chemotherapy drugs but if they are keeping people alive and giving them hope, that’s always a good thing.

I’ll get excited when researchers come up with effective drugs that don’t have side effects.

Reference articles:

http://www.nytimes.com/2012/06/03/health/research/in-study-drug-delays-worsening-of-breast-cancer-with-fewer-side-effects.html?_r=2&adxnnl=1&ref=health&src=me&adxnnlx=1344974462-qxirhUkbLGWgXzcVl83Qww

http://en.wikipedia.org/wiki/Trastuzumab_emtansine

http://healthyliving.msn.com/diseases/breast-cancer/is-tdm-1-a-miracle-drug-for-advanced-breast-cancer-1

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