AbstractBackgroundReproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.MethodsAnalyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2–like, HER2-enriched–like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided.ResultsCompared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2–like, and HER2-enriched–like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.ConclusionsThis large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.

中文翻译：

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内在样乳腺癌亚型的独特生殖风险概况：基于人群的研究的汇总分析


摘要背景生殖因素已被证明与雌激素受体 (ER) 阳性和 ER 阴性乳腺癌的风险存在差异相关。然而，它们与内在样亚型的关联尚不清楚。方法分析包括来自 4 大洲 16 个国家的乳腺癌协会联盟 31 项基于人群的病例对照或队列研究的多达 23 353 例病例和 71 072 例对照。使用多层次 Logistic 回归来评估生殖因素与乳腺癌风险之间的关联，这些亚型是内在样亚型（管腔 A 样、管腔 B 样、管腔 B-HER2 样、HER2 富集样和三阴性）乳腺癌）和侵袭性。所有统计检验均为双侧。结果与未产妇相比，已产妇女患管腔 A 样、管腔 B 样、管腔 B-HER2 样和 HER2 富集样疾病的风险较低。这种关联仅在距上次出生约 10 年后才显现出来，并随着时间的增加而变得更强（比值比 [OR] = 0.59，95% 置信区间 [CI] = 0.49 至 0.71；OR = 0.36，95% CI = 0.28 至对于患有腔内 A 样肿瘤的经产妇，在上次分娩后 20 至 25 年以内以及在上次分娩后 45 至 50 年内分别为 0.46）。相比之下，经产女性在最后一次分娩后患三阴性乳腺癌的风险较高（对于经产女性：OR = 3.12，95% CI = 2.02 至 4.83），这种风险随着时间的推移而减弱，但持续数十年（OR = 1.03） ，95% CI = 0.79 至 1.34，对于上次生育后 25 至不到 30 年的多产妇女）。首次生育年龄较大（与管腔 A 样乳腺癌相比，三阴性乳腺癌的 Pheterogeneity < .001）和母乳喂养（Pheterogeneity < .001）。001（与管腔 A 样乳腺癌相比，三阴性乳腺癌）与三阴性乳腺癌风险较低相关，但与其他疾病亚型无关。初潮年龄越小，所有亚型的风险越高；绝经年龄较大与管腔 A 型乳腺癌的风险较高相关，但与三阴性乳腺癌无关。原位肿瘤的关联与管腔 A 样肿瘤的关联相似。结论这项大型综合研究表明，与其他亚型相比，三阴性乳腺癌具有独特的生殖风险因素特征，这对于了解疾病病因和风险预测具有重要意义。