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Initial findings of the Women's Health Initiative (WHI) randomized trial of estrogen-progestin therapy suggested that risk for invasive breast cancer (hazard ratio, 1.26) was limited to women who had used hormone therapy (HT) longer than 5 years (Maturitas 2006 Sep; 55:103). Now, at a mean follow-up of 11 years, investigators report on breast cancer mortality in WHI participants.
Although tumor histology was similar in the HT and placebo groups, breast cancers in women who received combination HT were more likely to be node positive (23.7% vs. 16.2%; P=0.03). Breast cancer mortality was marginally raised with use of HT (2.6 vs. 1.3 deaths per 10,000 women per year among women randomized to HT and placebo, respectively [HR, 1.96; 95% confidence interval, 1.00–4.04]).
Chlebowski RT et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 2010 Oct 20; 304:1684.
Bach PB. Postmenopausal hormone therapy and breast cancer: An uncertain trade-off. JAMA 2010 Oct 20; 304:1719.
Comment
Earlier observational studies suggested that breast cancers in users of combined HT had more-favorable characteristics and were associated with lower mortality than were tumors in women who did not use HT. The current WHI report, which agrees with findings from the U.K. Million Women Study (Lancet 2003 Aug; 362:419), shows that breast cancer mortality is indeed higher in women who have used combination HT. With the publication of this important report, some will recommend that no menopausal woman should use HT. I intend to emphasize awareness of excess risk for breast cancer mortality when counseling patients who are considering initiating or continuing combination HT. These new findings also heighten the importance of exploring whether micronized progesterone combined with estrogen might have less effect on breast cancer mortality, a possibility raised by findings of the E3N cohort study (J Clin Oncol 2008 Mar; 26:1260). Finally, given the protection that HT offers against osteoporosis as well as the possibility that HT might be cardioprotective when begun within 10 years after menopause onset (JW Womens Health Apr 8 2010), a WHI report that addresses long-term all-cause mortality would be welcome.