2012 SAN ANTONIO BREAST CANCER SYMPOSIUM – WRAPPING UP SOME LOSE ENDS

There are many partially answered questions about the best ways to do things in breast oncology.  Several questions had great answers provided at this year’s San Antonio Breast Cancer Symposium (SABCS). Below is the newest information on how long to use adjuvant Herceptin (trastuzumab) and whether you can rely on a sentinel node biopsy after chemotherapy.

How long should a woman take trastuzumab (Heceptin)?

Trastuzumab, also known by the brand name, Hereptin, is the “poster child” for the future of targeted, individualized cancer treatment. 

About one-fifth of breast cancers have an overactive HER2 gene that makes the cancer more aggressive.  Trastuzumab literally reverses the effects of overactive HER2.  I’ve had patients with spread of cancer to their lungs and other places who’ve had what can only be described as a miraculous response to trastuzumab. 

More recently it has been shown that, if a woman’s breast cancer is tested and found to overexpress the HER2 gene, she will have better survival if she receives a year of trastuzumab before she has any evidence of spread of cancer.  This treatment before any evidence of metastasis is called “neoadjuvant treatment.”

The question has been whether one year of neoadjuvant trastuzumab is optimal.

Parallel tests of more or less traztizumab.

Two, back-to-back reports at the SABCS answered this question.  One study looked at whether 6 months of trastuzumab was not inferior to 1 year of treatment – a so-called “non-inferiority” test.  That’s’ a backwards way to ask if 6 months is as good as 12 months.  The researchers could not show that 6 months was as good as 12 months.

The other report looked at 2 years compared to 1 year of traztuzamab.  Many oncologists had assumed that, if one year worked, 2 years would be better.  It did not happen that way.  There was no improvement with the second year of trastuzumab. 

Answer:  One year of trastuzumab is just right.

Does sentinel lymph node biopsy work after chemotherapy?

Whether or not cancer has spread to nodes is a good guide in determining the best course of treatment to recommend.  For example, cancer in the nodes is a strong reason to consider chemotherapy, especially in younger women.

Using sentinel lymph node biopsy, also called SLNB, has helped doctors learn whether cancer is in nodes by evaluating only one or two or at most a few nodes.  This, in turn, has helped reduce the number of lymph nodes that are removed for the treatment of most women with early breast cancer.   The benefit of removing fewer nodes is a reduction in side effects of surgery such as lymphedema.  

Sometimes cancer is more advanced – possibly involving the nodes already – and it is desirable to give chemotherapy before surgery in order to shrink the cancer.  This can reduce the amount of tissue that must be removed from the breast, and thus improve cosmetic results.

The question has remained whether it is possible to rely on SLNB if the patient had chemotherapy before surgery.  It turns out there are three answers depending on what was done before chemotherapy began.  

Sentinel node when there has not been a node biopsy.

The easy situation is when a woman only had a biopsy of her breast to confirm that cancer was present, and then had chemotherapy without any node biopsy.  In this situation, SLNB is a reliable way to determine if there is cancer remaining in the nodes after the chemotherapy.  This has been known.  What has not been known is whether SLNB is reliable if a biopsy of a node was done to prove there was cancer in a node before chemotherapy was begun. 

Node surgery before chemotherapy can make sentinel node biopsy less reliable.

At SABCS, another pair of back-to-back presentations demonstrated that reliability of SLNB depends on the type of node biopsy that was done before chemotherapy.

If a SLNB was done as a surgical procedure – with isotope or blue dye node tracking, anesthesia, and a skin incision – then an attempt at a second SLNB after chemotherapy is not very reliable.  It finds the sentinel node only 61 percent of the time, and 52 percent of the time it was negative when another, different node had cancer – a so-called “false negative result.”  This is probably because the surgical SLNB scars the normal lymphatic channels that are needed for SLNB to work.

In contrast, if only a needle biopsy was done of a node before the chemotherapy, the results of SLNB are much more reliable.  There is a false negative result of only 13 percent.  If the surgeon uses two different ways to find the sentinel node, this false negative rate drops to 11 percent.  This is probably because using a needle to biopsy a node is much less disruptive of the lymphatic vessels.

In practice, this means that if the oncologist wants to know if a node is positive before administering chemotherapy, the pre-chemotherapy biopsy should be done with a needle rather than an open surgical biopsy.  That way, SLNB – with its benefits of less surgery and fewer side effects – can be used to assess the patient after the chemotherapy is complete. 

Answer:  Sentinel lymph node biopsy is reliable after chemotherapy if the nodes were not surgically biopsied before chemotherapy.   Remember, this information applies to the specific situation when chemotherapy is given before surgery to shrink a cancer and to improve the results of surgery.

More issues from SABCS in the next Perspectives on Women’s Health.

SAN ANTONIO BREAST CANCER SYMPOSIUM – TAMOXIFEN IN THE NEWS

Hearing presentations at the San Antonio Breast Cancer Symposium (SABCS) is kind of like watching your friend’s children grow up in their annual Christmas cards.   An idea will show up one year as a single presentation.  If it’s a good idea, there will be a few more papers the next year, and the following year, there will be a flood.  We’ve seen this with BRCA1 and 2 breast cancer genes, sentinel node surgery, trastuzumab (Herceptin), and efforts to map how genes cause cancer.  As ideas mature, they are applied to help patients. 

BPA arrived on the podium this year 

In 2011, my colleagues and I presented our work looking at the adverse effects of BPA (bisphenol-A) on normal human breast cells.  Ours was the only paper I had ever seen at the SABCS on any xenoestrogen. 

This year, the keynote speaker who opened the entire meeting (Dr. Cathrin Brisken from Switzerland) began her talk discussing how estrogens and progesterone contribute to cancer.  Then, midway through her talk, she changed her focus and spent the rest of her time saying that her own mice experiments have convinced her that BPA exposure can contribute to cancer development.  She was especially concerned about lifelong effects after BPA exposure of the fetus during pregnancy.

The next day, in a separate session on chemical modifications that alter how genes work (so called epigenetic modifications), the speaker (Dr. Tim Huang from Texas) reported BPA could cause ongoing changes in gene function without mutating the actual genes in cancer cells.  

It is exciting that the oncology community is realizing that real prevention of breast cancer is part of our job.  

Now, on to other topics. 

10 years of tamoxifen treatment is a little better than 5 years 

Since a 1991 report that more than 5 years of tamoxifen treatment might harm women, physicians in the United States have prescribed tamoxifen for only 5 years.  The British, however, were skeptical and did their own trial of 10 versus 5 years of tamoxifen.  Their study found that 10 years of tamoxifen treatment increased survival – a little bit. 

The effects of tamoxifen persist after the drug is discontinued

The interesting thing is that taking tamoxifen for 10 years did not have an effect while women took the drug between year 5 and year 10.  It only had an effect between year 10 and year 15.  This is puzzling until you realize that 5 years of tamoxifen has carryover effects, which is to say that the benefits of tamoxifen last 5 years after the drug is discontinued – whether or not a woman is still taking the drug.  Stated another way, taking tamoxifen between year 5 and year 10 did not have an effect because the patient already has the carryover effect, from the first 5 years, helping between year 5 and year 10.  You can’t make good be perfect. 

The reason 10 years of tamoxifen helps is that it has its own carryover effects that continue after treatment is stopped at 10 years.   Specifically, tamoxifen seems to have a benefit that lasts 5 years after it is stopped, whether it is stopped at 5 or 10 years.  

How big is the benefit from 10 years of tamoxifen?

This is fascinating biology, but the benefit is not huge.  On average, there is a 3% gain in survival for 10 years of tamoxifen versus 5 years.  It is important to understand, however, that this is the average gain obtained by combining results for high-risk and low-risk women.  For a woman with high risk – for example, a big tumor or multiple positive nodes – the benefit would be larger than average because her risk was larger to begin with.  For a woman who had a small tumor with negative nodes, the average benefit will be less than 3%.

What is the “cost” of tamoxifen? 

In the tamoxifen trial, women who took tamoxifen for 5 years had a 0.2 % chance of dying from cancer of the uterus caused by the tamoxifen itself.  For a woman who took tamoxifen for 10 years, this increased to 0.4 % chance of dying from cancer of the uterus caused by tamoxifen.   In both situations, a lot more women had to be treated for uterine cancer, but did not die from it.

These complications of tamoxifen occur independent of whether or not a woman gets a benefit.

Should women on tamoxifen take it for 10 years?

For a woman who had a high-risk cancer the English study supports keeping her on tamoxifen at least 7 years and probably 10 years.  [Or changing to an aromatase inhibitor if she has gone through menopause.]  

In contrast, when a woman has a lower risk, she has less to gain – but the same to lose from side effects – so she may decide not to take long term tamoxifen.  The risks of 10 years of tamoxifen may not be justified, because anything she gains might be offset by her chance of having an adverse side effect from the tamoxifen itself.

Other observations from SABCS to follow.