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.