背景:先前的研究表明,生殖因素与亚型之间的乳腺癌(BC)风险存在差异。这项研究的目的是调查生殖因素与BC亚型之间的关联。以及诊断时这些是否因年龄而异。
方法:我们使用了肿瘤标志物的汇总数据(雌激素和孕激素受体,人表皮生长因子受体2(HER2)和生殖风险因素(均等,来自参与乳腺癌协会联盟(BCAC)的34项研究的28,095例侵袭性BC患者的首次全职妊娠年龄(FFTP)和初潮年龄)。在仅案例分析中,我们使用logistic回归评估生殖因素与BC亚型之间的关联,并以管腔A肿瘤作为参考.还测试了BC亚型风险中年龄和均等之间的相互作用,在所有年龄段,因为年龄是非线性建模的,特别是35岁,55岁和75岁。
结果:ParouswomenweremorelikelytobedifiedwiththreenegativeBC(TNBC)thanwithluminalABC,与年龄无关(奇偶校验的OR=1.38,95%CI1.16-1.65,p=0.0004;与年龄相互作用的p=0.076)。Parous女性也更有可能被诊断为管腔和非管腔HER2样BC,并且这种影响在早期更为明显(与年龄的相互作用p分别为0.037和0.030)。例如,在35岁时诊断出的女性,与管腔ABC相比,管腔HER2样BC的可能性为1.48(CI1.01-2.16),而这种关联在75岁时不显著(OR=0.72,CI0.45-1.14)。而初潮年龄与BC亚型无显著相关性,相对于管腔ABC,FFTP年龄的增加与TNBC呈非线性相关。FFTP的年龄为25岁比20岁降低了TNBC的风险(OR=0.78,CI0.70-0.88,p<0.0001),但这种影响在后来的FFTP中并不明显。
结论:我们的主要发现表明,在BC诊断时,所有年龄段的产次都与TNBC相关。而与腔HER2样BC的关联仅存在于早发性BC。
BACKGROUND: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis.
METHODS: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a
case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years.
RESULTS: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p < 0.0001), but this effect was not apparent at a later FFTP.
CONCLUSIONS: Our main findings suggest that parity is associated with TNBC across all ages at BC diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC.