I am responding to an article in the January 25, 2020, issue of The ASCO Post on the conclusion of the 19-year follow-up on the Women’s Health Initiative (WHI) presented by Rowan T. Chlebowski, MD, PhD, at the 2019 San Antonio Breast Cancer Symposium: Postmenopausal estrogen administration does not increase the risk of breast cancer after all, he said, and, in fact, it may decrease the risk; the real culprit is estrogen combined with progesterone. Given that the WHI was largely responsible for frightening millions of women and their physicians into believing that “estrogen causes breast cancer”—a conclusion that it has been modifying and retracting over the past decade—it behooves us to try to understand what is really going on.
The current WHI update report that postmenopausal estrogen does not increase the risk of breast cancer is reinforced by other long-established findings in the medical literature, such as the 70% decrease in breast cancer risk associated with a full-term pregnancy before the age of 18; the lack of benefit resulting from an abortion at the time of breast cancer diagnosis; and the safety of pregnancy after treatment of breast cancer, even among estrogen receptor–positive women.
As for the alleged increased risk for women on combined hormones, consider this disconfirming evidence: progesterone deficiency is associated with a fivefold increase in the risk of breast cancer development1; progesterone has been shown to be as effective as tamoxifen in the treatment of breast cancer2; and progestin-alone contraceptives do not increase breast cancer recurrence.3 Thus, the WHI report of increased breast cancer risk among women randomly assigned to combination hormone replacement therapy appears inconsistent and warrants further explanation.
An explanation of the hormone replacement therapy anomaly was published in 2018,4 and it has nothing to do with the alleged risks of progesterone. It was caused by a lower-than-expected risk in the control group, against whom the combination hormone replacement therapy population was measured. This lowered risk appears to have resulted from including within the placebo group women who had taken estrogen prior to joining the study and who were randomly assigned to that placebo arm. When the risk was recalculated after these women were excluded, the increased risk observed among those randomly assigned to combination hormone replacement therapy had disappeared.
This remarkable analysis should have been incorporated into the 19-year interpretation of the results presented in San Antonio and published in The ASCO Post article.
—Avrum Bluming, MD
Emeritus Clinical Professor of Medicine
University of Southern California, Los Angeles
DISCLOSURE: Dr. Bluming has stock or other ownership interests in Intuitive Surgical, Johnson & Johnson, and Merck & Co.
1. Cowan LD, Gordis L, Tonascia JA, et al: Breast cancer incidence in women with a history of progesterone deficiency. Am J Epidemiol 114:209-217, 1981.
2. Van Veelen H, Willemse PH, Tjabbes T, et al: Oral high-dose medroxyprogesterone acetate vs tamoxifen: A randomized crossover trial in postmenopausal patients with advanced breast cancer. Cancer 58:7-13, 1986.
3. Strom BL, Berlin JA, Weber AL, et al: Absence of an effect of injectable and implantable progestin-only contraceptives on subsequent risk of breast cancer. Contraception 69:353-360, 2004.
4. Hodis HN, Sarrel PM: Menopausal hormone therapy and breast cancer: What is the evidence from randomized trials? Climacteric 21:521-528, 2018.
Disclaimer: Letters to the Editor represent the views of the author and may not necessarily reflect the views of ASCO or The ASCO Post.