Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor-defined invasive breast cancer

Purpose We previously found that the risk of invasive breast cancer varied according to the progestagen component of combined postmenopausal hormone therapy (CHT): progesterone, dydrogesterone, or other progestagens. We conducted the present study to assess how these CHTs were associated with histology- and hormone receptor-defined breast cancer. Patients and Methods We used data from the French E3N cohort study, with 80,391 postmenopausal women followed for a mean duration of 8.1 years; 2,265 histologically confirmed invasive breast cancers were identified through biennial self-administered questionnaires completed from 1990 to 2002. The relative risks (RRs) were estimated using Cox proportional hazards models. Results Compared with postmenopausal hormone therapy (HT) never-use, ever-use of estrogen + progesterone was not significantly associated with the risk of any breast cancer subtype, but increasing duration of estrogen + progesterone was associated with increasing risks of lobular (P = .06) and estrogen receptor-positive/progesterone receptor-negative (ER+/PR-; P = .02). Estrogen + dydrogesterone was associated with a significant increase in risk of lobular carcinoma (RR, 1.7; 95% CI, 1.1 to 2.6). Estrogen + other progestagens was associated with significant increases in risk of ductal and lobular carcinomas (RR, 1.6; 95% CI, 1.3 to 1.8; and 2.0; 95% CI, 1.5 to 2.7, respectively), of ER+/PR+ and ER+/PR- carcinomas (RR, 1.8; 95% CI, 1.5 to 2.1; and 2.6; 95% CI, 1.9 to 3.5, respectively), but not of ER+/PR- or ER+/PR- carcinomas (RR, 1.0; 95% CI, 0.5 to 2.1; and 1.4; 95% CI, 0.9 to 2.0, respectively). Conclusion The increase in risk of breast cancer observed with the use of CHTs other than estrogen + progesterone and estrogen + dydrogesterone seems to apply preferentially to ER + carcinomas, especially those ER+/PR-, and to affect both ductal and lobular carcinomas.