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Invited Commentary
April 24, 2020

Progesterone Exposure and Breast Cancer Risk—Addressing Barriers

Author Affiliations
  • 1Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicaqgo, Illinois
JAMA Netw Open. 2020;3(4):e203608. doi:10.1001/jamanetworkopen.2020.3608

Exposure to endogenous sex hormones has long been recognized as an important (albeit unavoidable) source of risk for cancer, particularly of reproductive organs. Studies addressing the breast cancer risk associated with endogenous hormone exposures have reported the increased breast cancer risk experienced by postmenopausal women who have higher than average serum levels of estradiol and its androgenic precursors. For example, in the European Prospective Investigation into Cancer and Nutrition cohort, the relative risk of breast cancer per doubling of serum estradiol in women sampled when postmenopausal was 1.31 (95% CI, 1.08-1.58).1 Of note, the European Prospective Investigation into Cancer and Nutrition investigators did not measure progesterone levels in postmenopausal women “as ovarian progesterone synthesis ceases after menopause.”1(p4183) The understudied possibility that progesterone exposure may be associated with breast cancer risk is highly relevant, particularly because efforts are under way to develop natural progesterone as a safe alternative to progestins in menopausal hormone therapy regimens.2

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    1 Comment for this article
    Clarification regarding B~FIT study
    Britton Trabert, PhD, MS | Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS
    I'd like to thank Dr. Khan for the insightful commentary. The participants included in the B~FIT case-cohort study had no reported use of exogenous hormones in the 4 months prior to blood draw, this is noted in Figure 2.

    Although it is not included in the manuscript, we did evaluate the risk of breast cancer per standard deviation increase in progesterone concentration across categories of prior MHT use (HR per SD increase in progesterone among never/<1 year prior MHT users, 1.20; 95% CI, 0.99-1.47; HR per SD increase in progesterone among ≥1 year prior MHT users, 1.11; 95%
    CI, 0.91-1.36; P=0.22 for interaction).