Breast cancer outcome and estrogen plus progestin use in postmenopausal women.

Abstract

1507 Background: During a mean (SD) 5.6 years (1.3) of intervention, use of estrogen plus progestin in the Women's Health Initiative (WHI) randomized clinical trial increased breast cancer incidence (Chlebowski et al JAMA 2003;289;3243) but breast cancer mortality was not reported. Therefore, we determined combined hormone therapy effects on breast cancer incidence and mortality in the WHI trial over the entire follow-up period (mean [SD] 11.0 [2.7] years) and also in the WHI observational study cohort. Methods: In the clinical trial, 16,608 postmenopausal women with no prior hysterectomy were randomized to conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) (estrogen plus progestin) or placebo. In the observational study, 41,449 postmenopausal women with characteristics similar to clinical trial participants were identified at entry as estrogen plus progestin users (n = 16,121) or not users (n = 25,328). Main outcome measures included invasive breast cancer incidence and breast cancer mortality. Results: In the clinical trial, more breast cancers were diagnosed in the estrogen plus progestin group (385 vs. 293; HR, 1.25; 95% CI, 1.07-1.46, p = 0.004) and the breast cancers were more likely to be node positive (p = 0.02). Deaths directly attributed to breast cancer were greater in the estrogen plus progestin group (25 vs. 12 deaths; HR 1.96 95% CI 1.01-4.05, p = 0.048) as were deaths from all causes occurring after a breast cancer diagnosis (49 vs. 31 deaths; HR 1.51 95% CI 0.97-2.39, p = 0.07). Estrogen plus progestin users in the observational study had somewhat more deaths attributed to breast cancer (HR 1.33 95% CI 0.82-2.16, p = 0.26) and more deaths from all causes occurring after a breast cancer diagnosis (HR 1.82, 95% CI 1.33-2.50, p < 0.001) compared to women not using estrogen plus progestin at entry. Conclusions: Estrogen plus progestin use increases breast cancer incidence with cancers more commonly node positive. Mortality from all causes after a breast cancer occurrence was greater and an adverse trend for deaths attributed to breast cancer is seen with combined hormone therapy use. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Lilly, Novartis, Pfizer, Procter and Gamble, Upsher-Smith Laboratories, Wyeth Abraxis BioScience, AstraZeneca, Novartis Amgen, Lilly, Organon, Procter and Gamble, Wyeth