Regarding an article in the NY Times on reducing breast cancer threat

Last week, Jane Brody, in her column, wrote about screening for breast cancer and early detection with mammograms as well as the confusion about who should get mammograms and at what frequency. This week, as the second of a two-part series, her article is entitled, “How to Reduce Breast Cancer Threat.”

Much of what she writes about is absolutely true and not necessarily new. The relationship of alcohol to breast cancer is well known, although, moderate consumption of wine seems to result in reduced cardiovascular risk. Being overweight, since adipose tissue makes a weak form of non-ovarian estrogen called estrone, puts such patients at slightly increased risk of breast cancer.

She then delves into hormone replacement and quotes the recent article in JAMA that looked at long-term effects on breast cancer risk of hormone replacement. I have discussed these studies with many of you. It is well known that the women who took Prempro (that’s Premarin and Provera) had an increased risk of developing breast cancer as well as a trend toward increase rate of death from breast cancer (this was not quite statistically significant). She also mentions that the use of estrogen by itself resulted in a reduction in breast cancer risk. I have been clear to you and anyone that I lecture that there is no such thing as estrogen! There are estrogens. Premarin comes from pregnant horses’ urine and consists of estradiol (the natural ovarian estrogen) as well as a multitude of other substances. It becomes obvious that Premarin, unlike plain estradiol, has some constituents in it that have SERM-like properties. SERMs are selective estrogen receptor modulators like Evista or tamoxifen that are anti-estrogens in breast but estrogenic in bone. That is why women on Premarin alone had a reduction in breast cancer. Estradiol has not been shown to reduce breast cancer like Premarin did. 

She does not mention a new paradigm, which should revolutionize hormone replacement therapy but never will because of the constraints of the FDA labeling process. Pfizer figured out how to protect the uterine lining (endometrium) with a different SERM called bazedoxifene. It has thus paired Premarin (which has been shown to reduce breast cancer risk and breast cancer death) with that SERM bazedoxifene. All of the SERMs are anti-estrogen in breast. From a scientific point of view, combining Premarin with a SERM will result in a reduction in breast cancer risk. The magnitude of such a reduction, however, is not studied and probably never will be. Such a test would be a massive expense, which has caused Pfizer to decide there is not enough return on investment. This compound, Duavee, is approved for treating menopausal symptoms (hot flashes, and night sweats) and preventing the bone loss that occurs with menopause. It also, undoubtedly, will have benefits in vagina as well as, mentioned above, reduce breast cancer risk. It is unfortunate that this new paradigm is one of the best-kept secrets in medicine. It has been around since 2013! It seems that only the key opinion leaders (often known as KOLs) are aware of the science of this compound. This is frustrating. It is so irritating when a mammography doctor tells one of my Duavee patients, “are you crazy to take hormones. You are going to increase your risk of breast cancer.” Nothing could be further from the truth. 

Finally, she does mention drugs that are used to prevent breast cancer and are approved. These include the SERMs Evista and tamoxifen. However, she also mentions the other class called aromatase inhibitors. Although these are approved, I feel strongly that it would be fool hardy to take an aromatase inhibitor for prevention of breast cancer. These drugs totally reduce any estrogen circulating resulting in the increased likelihood of osteoporosis, often with joint pain, and making vaginal atrophy worse. Women at high-risk for developing breast cancer, in my opinion, should take SERMs like tamoxifen and raloxifene. I would not suggest aromatase inhibitors for prevention. They are very effective drugs in women who have anything beyond Stage 1 breast cancer. 

Hoping this is valuable to you or someone in your family.