很少有研究调查妊娠相关因素与乳腺癌 (BC) 风险之间的关联是否因潜在的 BC 易感性而异。有关 BC 风险变化的证据对于了解 BC 原因和制定有效的基于风险的筛查指南至关重要。检查妊娠相关因素与 BC 风险之间的关联，包括根据年龄和 BC 家族对 BC 进行修改该队列研究包括来自前瞻性家庭研究队列 (ProF-SC) 的参与者，其中包括乳腺癌家庭登记处的 6 个站点（美国、加拿大和澳大利亚）和凯瑟琳·坎宁安基金会联盟（澳大利亚）。对 1992 年至 2011 年期间招募的没有任何 BC 个人病史的女性队列进行了分析，对她们进行了随访至 2017 年，中位（范围）随访时间为 10（1-23）年。数据分析时间为 1992 年 3 月至 2017 年 3 月。产次、足月妊娠 (FTP) 次数、首次 FTP 年龄、距上次 FTP 的年数以及母乳喂养情况。BC 诊断通过自我报告或一级报告获得相关并通过病理学和数据链接得到证实。 Cox 比例风险回归模型估计每次暴露的风险比 (HR) 和 95% CI，并检查 BC 的 PARS 的修改。通过雌激素受体 (ER) 亚型评估差异。该研究包括 17274 名女性（平均 [SD] 年龄，46.7 [15.1] 岁；791 名非裔美国人或黑人参与者 [4.6%]，1399 名西班牙裔或拉丁裔参与者 [8.2%] ，以及 13790 名白人参与者 [80.7%]），其中有 943 例前瞻性确定的 BC 病例。与未生育过的女性相比，PARS 较高的女性在最近怀孕后的 BC 风险更高（最近 FTP 0-5 年相互作用的 HR，1.53；95% CI，1.13-2.07；相互作用的 P < .001）。其他暴露之间的关联仅限于 ER 阴性疾病。 ER 阴性 BC 与 PARS 的增加和自上次 FTP 以来年数的增加呈正相关（交互作用 P < .001），与未生育女性相比，近期怀孕的风险更高（上次 FTP 0-5 年交互作用的 HR，1.54；95% CI， 1.03-2.31）。 ER 阴性 BC 与 PARS 增加、首次 FTP 时年龄为 20 岁或以上与 20 岁以下呈正相关（相互作用 P = .002），与多产与未产呈负相关（相互作用 P = .01）。在这项针对既往没有 BC 诊断的女性的队列研究中，妊娠相关因素与 BC 风险之间的关联通过 PARS 进行了修改，观察到 ER 阴性 BC 的关联更大。

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.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.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.Parity, number of full-term pregnancies (FTP), age at first FTP, years since last FTP, and breastfeeding.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.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 < .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 < .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).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.