Abstract 4176: Timing of pregnancy-related factors and breast cancer risk for women across a range of absolute risk
Authors: McDonald Jasmine A. , Liao Yuyan , John Esther M. , Kurian Allison W. , Genkinger Jeanine M. , Buys Saundra S. , Hopper John L. , Investigators kConFab , Terry Mary Beth 
Published: April 2023

Abstract
Background: Studies in women with pathogenic variants in BRCA1 or BRCA2 suggest that underlying breast cancer (BC) risk modifies the associations between pregnancy-related factors and BC risk. Less is known about whether the associations are modified across a range of predicted absolute BC risk based on age and the extent of BC family history.
Objective: Examine the association between pregnancy-related factors and BC risk and modification by predicted absolute BC risk in the Prospective Family Study Cohort (ProF-SC) with women enrolled between 1992-2011 and a median 10.0 years of follow-up time.
Methods: ProF-SC includes the six international sites of the Breast Cancer Family Registry [USA, Canada, and Australia] and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). 17,274 women with 943 prospectively ascertained BC cases were eligible for the prospective analysis with 87% of cases self-identifying as non-Hispanic White. Questionnaires at study entry assessed self-reported pregnancy-related factors (parity, number of full-term pregnancies (FTP), age at first FTP, years since last FTP, breastfeeding, and age at menarche). We used Cox proportional hazards regression models with age as a time scale to estimate Hazard Ratios (HR) and the 95% Confidence Intervals (CI) for each reproductive variable (main effect) and examined modification by predicted absolute risk of BC, measured by a 1-year absolute risk score (continuous) estimated by the BOADICEA (interaction effect). We also examined associations stratified by estrogen receptor (ER) subtype.
Results: Women with a first FTP at age ≥30 vs. &lt;20 years had an increased risk of BC (HR=1.49, 95% CI 1.10, 2.02); no other pregnancy-related factors were associated with BC risk. Compared to nulliparous women, the main effect for higher parity was associated with increased ER-negative BC (PARS*≥4 FTP HR 2.34, 95% CI 1.09, 5.01). In contrast, increasing absolute BC risk for women with higher parity was associated with reduced risk of ER-negative BC (PARS*≥4 FTP HRinteraction 0.66, 95% CI 0.48, 0.90; pinteraction=0.01). Increasing absolute BC risk for nulliparous or first FTP at age ≥25 years had a &gt;20% increased risk of ER-negative BC compared to first FTP at age &lt;20 years (pinteraction=0.002); the main effects for nulliparity and first FTP at age ≥25 years and ER-negative BC were null (p-values=0.2-1.0). Compared to nulliparous women, increasing absolute risk for women who were within 5 years of their last FTP was positively associated with ER-negative BC (HRinteraction=1.54, 95% CI 1.03, 2.31); main effects were null (HR=1.00, 95% CI 0.39, 2.54).
Conclusion: The association between pregnancy-related factors and BC risk are modified by predicted absolute BC risk, with stronger associations observed for ER-negative BC. Women at higher absolute BC risk may benefit from more frequent BC monitoring following childbirth.
Citation Format: Jasmine A. McDonald, Yuyan Liao, Esther M. John, Allison W. Kurian, Jeanine M. Genkinger, Saundra S. Buys, John L. Hopper, kConFab Investigators, Mary Beth Terry. Timing of pregnancy-related factors and breast cancer risk for women across a range of absolute risk. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4176.