Pregnancy-Related Factors and Breast Cancer Risk for Women Across a Range of Familial Risk

Importance Few studies have investigated whether the associations between pregnancy-related factors and breast cancer (BC) risk differ by underlying BC susceptibility. Evidence regarding variation in BC risk is critical to understanding BC causes and for developing effective risk-based screening guidelines. Objective To examine the association between pregnancy-related factors and BC risk, including modification by a of BC where scores are based on age and BC family history. Design, Setting, and Participants This cohort study included participants from the prospective Family Study Cohort (ProF-SC), which includes the 6 sites of the Breast Cancer Family Registry (US, Canada, and Australia) and the Kathleen Cuningham Foundation Consortium (Australia). Analyses were performed in a cohort of women enrolled from 1992 to 2011 without any personal history of BC who were followed up through 2017 with a median (range) follow-up of 10 (1-23) years. Data were analyzed from March 1992 to March 2017. Exposures Parity, number of full-term pregnancies (FTP), age at first FTP, years since last FTP, and breastfeeding. Main Outcomes and Measures BC diagnoses were obtained through self-report or report by a first-degree relative and confirmed through pathology and data linkages. Cox proportional hazards regression models estimated hazard ratios (HR) and 95% CIs for each exposure, examining modification by PARS of BC. Differences were assessed by estrogen receptor (ER) subtype. Results The study included 17 274 women (mean SD age, 46.7 15.1 years; 791 African American or Black participants 4.6%, 1399 Hispanic or Latinx participants 8.2%, and 13 790 White participants 80.7%) with 943 prospectively ascertained BC cases. Compared with nulliparous women, BC risk was higher after a recent pregnancy for those women with higher PARS (last FTP 0-5 years HR for interaction, 1.53; 95% CI, 1.13-2.07; P for interaction lt; .001). Associations between other exposures were limited to ER-negative disease. ER-negative BC was positively associated with increasing PARS and increasing years since last FTP ( P for interaction lt; .001) with higher risk for recent pregnancy vs nulliparous women (last FTP 0-5 years HR for interaction, 1.54; 95% CI, 1.03-2.31). ER-negative BC was positively associated with increasing PARS and being aged 20 years or older vs less than 20 years at first FTP ( P for interaction = .002) and inversely associated with multiparity vs nulliparity ( P for interaction = .01). Conclusions and Relevance In this cohort study of women with no prior BC diagnoses, associations between pregnancy-related factors and BC risk were modified by PARS, with greater associations observed for ER-negative BC.