Association between chronological change of reproductive factors and breast cancer risk defined by hormone receptor status: results from the Seoul Breast Cancer Study

Lifestyle factors have been chronologically changed into western style ones, which could result in the rapid increase of breast cancer incidence in Korea. It is plausible that reproductive factors through hormonal mechanisms are differentially related to the risk of breast cancer subtypes. We investigated the association of reproductive risk factors on breast cancer by birth year groups and also evaluated the differential associations on the hormone receptor-defined subtypes. Using the data from the Seoul Breast Cancer Study (SeBCS), a multicenter case-control study, 3,332 breast cancer patients and 3,620 control subjects were analyzed. The distribution of subtypes among cases was as follows: 61.0 % estrogen receptor (ER)-positive, 51.9 % progesterone receptor (PR)-positive, and 43.4 % both ER/PR-positive status, respectively. Polytomous logistic regression and Wald tests for heterogeneity have been used across the subtypes. The frequencies of reproductive-related risk factors including early age at menarche, nulligravid, age at first full-term pregnancy (FFTP), duration of estrogen exposure before FFTP (EEBF), less number of children, never breastfeeding, and short duration of breastfeeding has increased as women were born later in both cases and controls, respectively (p (trend) < 0.0001. Among breast cancer patients, either ER- or PR-positive subtypes were increased in women born in 1960s compared to women born in 1940s. Early age at menarche increased the risk of breast cancer regardless of the subtypes while nulligravid, late age at FFTP, and longer duration of EEBP were associated with hormone receptor-positive cancer risk only (p (heterogeneity) < 0.05), which associations were stronger among women born later. Our results suggest that the associations of age at menarche, parity, age at FFTP, and duration of EEBF with breast cancer risk were different based on the hormone receptor status and birth year groups in Korea.