Pregnancy-Related Factors and Breast Cancer Risk for Women Across a Range of Familial Risk
Authors: McDonald Jasmine A. , Liao Yuyan , Knight Julia A. , John Esther M. , Kurian Allison W. , Daly Mary , Buys Saundra S. , Huang Yun , Frost Caren J. , Andrulis Irene L. , Colonna Sarah V. , Friedlander Michael L. , Hopper John L. , Chung Wendy K. , Genkinger Jeanine M. , MacInnis Robert J. , Terry Mary Beth ,   Kathleen Cuningham Foundation Consortium investigators, Amor David , Andrews Lesley , Antill Yoland , Balleine Rosemary , Beesley Jonathan , Bennett Ian , Bogwitz Michael , Bodek Simon , Botes Leon , Brennan Meagan , Brown Melissa , Buckley Michael , Burke Jo , Butow Phyllis , Caldon Liz , Campbell Ian , Cao Michelle , Chakrabarti Anannya , Chauhan Deepa , Chauhan Manisha , Chenevix-Trench Georgia , Christian Alice , Cohen Paul , Colley Alison , Crook Ashley , Cui James , Courtney Eliza , Cummings Margaret , Dawson Sarah-Jane , deFazio Anna , Delatycki Martin , Dickson Rebecca , Dixon Joanne , Edwards Stacey , Farshid Gelareh , Fellows Andrew , Fenton Georgina , Field Michael , Flanagan James , Fong Peter , Forrest Laura , Fox Stephen , French Juliet , Friedlander Michael , Gaff Clara , Gattas Mike , George Peter , Greening Sian , Harris Marion , Hart Stewart , Harraka Philip , Hayward Nick , Hopper John , Hoskins Cass , Hunt Clare , James Paul , Jenkins Mark , Kidd Alexa , Kirk Judy , Koehler Jessica , Kollias James , Lakhani Sunil , Lawrence Mitchell , Lee Jason , Li Shuai , Lindeman Geoff , Lippey Jocelyn , Lipton Lara , Lobb Liz , Loi Sherene , Mann Graham , Marsh Deborah , McLachlan Sue Anne , Meiser Bettina , Milne Roger , Nightingale Sophie , O'Connell Shona , O'Sullivan Sarah , Gallego Ortega David , Pachter Nick , Pang Jia-Min , Pathak Gargi , Patterson Briony , Pearn Amy , Phillips Kelly , Pieper Ellen , Ramus Susan , Rickard Edwina , Ragunathan Abi , Robinson Bridget , Saleh Mona , Skandarajah Anita , Salisbury Elizabeth , Saunders Christobel , Saunus Jodi , Savas Peter , Scott Rodney , Scott Clare , Sexton Adrienne , Shaw Joanne , Shelling Andrew , Srinivasa Shweta , Simpson Peter , Southey Melissa , Spurdle Amanda , Taylor Jessica , Taylor Renea , Thorne Heather , Trainer Alison , Tucker Kathy , Visvader Jane , Walker Logan , Williams Rachael , Winship Ingrid , Young Mary Ann , Zaheed Milita 
Published: August 2024

ImportanceFew 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresParity, number of full-term pregnancies (FTP), age at first FTP, years since last FTP, and breastfeeding.Main Outcomes and MeasuresBC 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.ResultsThe 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 &amp;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 &amp;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 RelevanceIn 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.