Spring is the season for medical meetings, and this year was more hectic than ever! Now that things have settled down, and I’m finally getting the chance to reflect on what I have learned from the latest research.
It’s clear that the promise of targeted therapy is starting to come to fruition. At the American Society for Clinical Oncology meeting, we got the very exciting news that a new class of drugs, called PARP2 inhibitors, target triple negative breast cancers effectively, with minimal side effects in women with metastatic disease who have already tried several kinds of chemotherapy. If you have metastatic breast cancer that is triple negative, you may want to look for a clinical trial that is investigating this new treatment.
Even more interesting is the increasing data that shows that cancer as a disease requires more than just mutated cells but also a supportive local environment. In fact, most of us probably have small nests of cancer cells lying dormant in our body. We need to understand what it is that wakes these cells up, and whether and how we can we put them back to sleep. This is probably how hormone replacement therapy (HRT) had its effect on breast cancer cells so quickly. It did not cause cells to mutate; it changed the local environment around the tumor in ways that stimulated the cancer cells to grow.
At a meeting I attended that focused specifically on mammographic breast density, investigators presented data showing that most of the density represents an increase in fibrosis tissue. This means that the density is due to excess connective tissue. The Breast Cancer Prevention Trial, which was designed to see whether taking tamoxifen could prevent breast cancer in high-risk women, found that only the women whose mammograms became less dense on tamoxifen had a reduced breast cancer risk. In the women whose mammograms did not change, tamoxifen had no effect. This could reflect the tissue’s sensitivity to tamoxifen. Or it could be related to another hot topic: how tamoxifen is metabolized.
About 10 percent of all women lack an enzyme, called CYP2D6, which converts tamoxifen into its active ingredient, endoxifen, and these women are probably not benefitting from tamoxifen. (Studies have shown that women who lack this enzyme rarely have side effects when they are on tamoxifen, so if you are not having side effects, you should mention this to your doctor.)
These findings underscore that when we think about a tumor and its molecular biology, we need to take into account not only how permissive the surrounding tissue is to the cancer cells, but whether the drug a woman is taking is being metabolized properly. While this may seem daunting it also gives us lots of ways to influence a cancer beyond slash, burn, and poison! Maybe we just need to learn what “lullaby” these cells need to hear to put them back to sleep!
I’ll be thinking about what this “lullaby” might be this summer. I’m also, as I noted last month, immersed in writing the 5th edition of the Breast Book. Thank you to everyone who sent in a story about benign breast problems and plastic surgery. As we move closer to publication, we will let you know if we will be using your story in the book. Now, I’m looking for stories from women who have had DCIS or LCIS and from women who made the decision to be tested for BRCA1 and 2. If you’d like to share your experience, please send me an email. I look forward to hearing your stories!
With appreciation and gratitude,
Dr. Susan Love