Interaction Effect Between Breast Density and Reproductive Factors on Breast Cancer Risk in Korean Population.

Background: This study was conducted to explore the effect of known risk factors, focusing on risk factors including age at menarche, age at menopause, number of children, family history of breast cancer, and age at first birth according to breast density, in consideration of interaction among East-Asian women.

Methods: Case-control study with 2,123 cases and 2,121 controls with mammographic density was conducted. Using the mammographic film, breast density was measured using Breast Imaging-Reporting and Data System. To identify the association of selected reproductive factors including age at menarche, age at menopause, number of children, family history of breast cancer, and age at first birth according to breast density, stratified analysis was conducted according to breast density groups and interaction effects was assessed. The results were presented with adjusted OR and 95% CIs.

Results: Significant interaction effect between age at first birth and breast density on breast cancer ( = 0.048) was observed. Women with age at first birth ≥ 28 years old showed increased breast cancer risk in extremely dense breast group (≥ 75%) (OR = 1.627, 95% CI = 1.190-2.226). However, women with fatty breast (< 50%) and heterogeneously dense breast (50%-75%) did not show an increased association. Age at menarche, age at menopause, number of children, and family history of breast cancer did not show significant interaction with breast cancer and similar risk patterns were observed.

Conclusions: Age at first birth showed significant interaction with breast density on breast cancer risk. Further studies considering biologically plausable model between exposure, intermediate outcomes and breast cancer risk with prospective design need to be undertaken in East Asian women.