Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women

Abstract

Context

In the Women's Health Initiative estrogen plus progestin trial, after mean (SD) intervention of 5.6 (1.3) years (range 3.7 to 8.6 years) and mean follow-up of 7.9 (1.4) years, breast cancer incidence was increased by combined hormone therapy. However, breast cancer mortality results have not been previously reported.

Objective

To determine estrogen plus progestin effects on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (2.7) years thru August 14, 2009.

Design, Setting, and Participants

16,608 postmenopausal women, aged 50-79 years with no prior hysterectomy, were randomly assigned to combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo. After the original trial completion date (March 31, 2005) re-consent was required for continued follow-up for breast cancer incidence and was obtained in 83%.

Main outcome measures

Invasive breast cancer incidence and breast cancer mortality.

Results

In intent-to-treat analyses including all randomized participants, censoring those on March 31, 2005 not-consenting for additional follow-up, estrogen plus progestin increased invasive breast cancers compared with placebo (385 [0.42%/yr] vs 293 [0.34%/yr] cases; hazard ratio [HR] 1.25, 95% confidence interval (CI) 1.07-1.46; P=.004). The breast cancers in the estrogen plus progestin group were similar in histology and grade but were more likely to be node positive (81 [23.7%] vs 43 [16.2%], respectively; P=0.03). Deaths directly attributed to breast cancer were greater in the estrogen plus progestin group (25 [0.03%/yr] vs 12 [0.01%/yr] deaths; HR, 1.96; 95% CI 1.00-4.04, P=.049) as were deaths from all causes occurring after a breast cancer diagnosis (51 [0.05%/yr] vs 31 [0.03%/yr] deaths; HR 1.57, 95% CI 1.01-2.48; P=.045).

Conclusions

Estrogen plus progestin increases breast cancer incidence with cancers more commonly node positive. Breast cancer mortality also appears to be increased with combined estrogen plus progestin use.