Reproductive factors and breast cancer risk in relation to hormone receptor and menopausal status in Japanese women

The associations between menstrual and reproductive factors and breast cancer risk in relation to estrogen/progesterone receptor (ER/PgR) status have been unclear in Japanese women. This case-control study evaluated these associations, overall and separately, by menopausal status. A total of 1092 breast cancer cases and 3160 controls were selected from among female patients aged 30 years and over admitted to a single hospital in Miyagi Prefecture between 1997 and 2009. The receptor status distribution among the cases (missing: 8.4%) was 571 ER+/PgR+, 133 ER+/PgR-, 24 ER-/PgR+ and 271 ER-/PgR- Menstrual and reproductive factors were assessed using a self-administered questionnaire. Polytomous logistic regression and tests for heterogeneity across ER+/PgR+ and ER-/PgR- were conducted. Later age at menarche was significantly associated with a decreased risk of both ER+/PgR+ and ER-/PgR- cancer among women overall (P_trend = 0.0016 for ER+/PgR+; P_trend = 0.015 for ER-/PgR-) and among postmenopausal women (P_trend = 0.012 for ER+/PgR+; P_trend = 0.0056 for ER-/PgR-). Nulliparity was associated with an increased risk of ER+/PgR+, but not ER-/PgR- cancer among women overall (P_{heterogeneity} = 0.019) and among postmenopausal women (odds ratio for ER+/PgR+ = 2.56, 95% confidence interval = 1.61-4.07; P_{heterogeneity} = 0.0095). A longer duration of breastfeeding tended to be associated with a decreased risk in all subtypes among women overall. Later age at menarche has a protective effect against both ER+/PgR+ and ER-/PgR- cancer. However, parity might impact differently on various subtypes of breast cancer. Further studies are needed to clarify the etiology of the rare ER+/PgR- and ER-/PgR+ cancer subtypes.