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Hormone replacement therapy and breast cancer risk

Tuesday, September 1, 2015

Ongoing analysis of data from the Women’s Health Initiative (WHI) reveals that even years after treatment has ended, postmenopausal women who took estrogen and progestin continue to have a greater chance of developing breast cancer. A new analysis of two WHI clinical trials, reported recently in JAMA Oncology, investigated the post-intervention phase of the studies to get a deeper look at the after effects of hormone replacement therapy (HRT) on coronary heart disease and invasive breast cancer. Tessa Cigler, M.D., was invited to write a commentary on the study for Clinical Oncology News. Read the full article here.

Tessa Cigler, M.D.Tessa Cigler, M.D. Results of the WHI that demonstrated an increased risk for breast cancer among women who used combination estrogen and progesterone HRT were published in 2002. Almost immediately, the routine use of HRT among menopausal women plummeted, and epidemiologic studies tracked a concomitant decline in breast cancer incidence. Dr. Cheblowski et al recently published updated results of two WHI trials, including reports of breast cancer risk in the years following cessation of HRT, with the idea of providing a better understanding of the temporal effects of both combined E+P and estrogen replacement therapy on breast cancer risk.

 The trials can be commended for their large sample size, with over 16,000 and 10,000 participants, respectively, their randomized and placebo-controlled design, and the fact that, unlike many other HRT trials, both treatment and placebo arms had similar rates of mammogram usage.

What has emerged is “a complex pattern of changing year-to-year influences,” whereby cessation of E+P was associated with an initial decline and a subsequent steady increase in breast cancer risk, whereas cessation of estrogen was associated with decreased risk that abated over time.

The results confirm that combination HRT increases breast cancer risk, likely to an even greater extent than previously believed. Certainly, women interested in combination HRT need to be counseled accordingly. Encouragingly, the sustained decreased risk for breast cancer associated with estrogen monotherapy suggests that for women without a uterus, estrogen may prove to be a safer option for HRT. Importantly, this study provides increasing evidence for a prominent role of progesterone in breast cancer pathogenesis, and may spark research designed to identify new therapeutic targets and interventions for the prevention and treatment of breast cancer.