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Estrogen-Progestin Therapy and Risk for Breast Cancer: More Findings from the WHI

Postintervention WHI data show risk rose during, and fell after, use of combination HT.

In a key finding from the Women’s Health Initiative (WHI) randomized trial of estrogen plus progestin hormone therapy, risk for breast cancer rose moderately after 5 years of HT use. Now, WHI investigators have analyzed trends in breast cancer diagnoses in relation to HT use and discontinuation in WHI clinical trial participants as well as in those enrolled in a WHI observational study.

For women who received HT in the clinical trial, risk for breast cancer climbed with each year of study drug administration until the intervention phase was terminated in 2002; therefore, overall risk was higher during the 5.6-year intervention phase than it was before initiation of HT (hazard ratio, 1.26). During 2.5 years of postintervention follow-up, breast cancer HRs as well as incidence declined rapidly. Very few participants who had been assigned to the intervention arm elected to continue HT use with their own providers after the intervention phase was terminated.

Among participants in the observational study, risk for breast cancer associated with use of combination HT (mean duration of use, 6.9 years) was elevated approximately twofold but declined after 2002; HRs were 1.0 in 2003 and 2004. HT use by these women declined after announcement of the clinical trial findings in 2002, and subsequent incidence of breast cancer dropped among participants who had entered the study as HT users.

Comment: Changes in prevalence of screening mammography did not account for the observed trends in risk for or incidence of breast cancer associated with HT use in either study. Among WHI participants who were exposed to estrogen plus progestin HT, risk for breast cancer declined rapidly after they discontinued therapy. The mechanism of this rapid decline could be related to direct hormonal effects on the growth of occult breast cancers. If so, a reasonable question is whether the decline in breast cancer incidence after the highly publicized publication of the initial WHI results will be durable or whether breast cancer incidence will rise again after HT use stabilizes among U.S. women (JW Oncol Hematol May 14 2007).

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health February 4, 2009

Citation(s):

Chlebowski RT et al. Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med 2009 Feb 5; 360:573.

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  Carla M Evans, 7 Jan 2010 2:45 PM EST
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