John Esther M, Koo Jocelyn, Ingles Sue A, Keegan Theresa H, Gomez Scarlett L, Haiman Christopher A, Kurian Allison W, Kwan Marilyn L, Neuhausen Susan L, Shariff-Marco Salma, Thomsen Catherine, Wu Anna H, Cheng Iona
Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, United States.
Department of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA, United States.
J Natl Cancer Inst. 2025 Mar 1;117(3):436-449. doi: 10.1093/jnci/djae254.
Epidemiological studies of risk factors for second primary breast cancer (SBC) have been conducted primarily in non-Hispanic White (NHW) women.
A racially and ethnically diverse population-based pooled cohort of 9639 women with first primary stage I-III invasive breast cancer (FBC) was linked with the California Cancer Registry; 618 contralateral SBC (CSBC) and 278 ipsilateral SBC (ISBC), diagnosed more than 6 months after FBC, were identified. Using Fine and Gray models accounting for competing risks, we assessed associations of CSBC and ISBC risk with FBC clinical characteristics and epidemiological factors.
In younger women (FBC at age <50 years), higher CSBC risk was associated with ER/PR-negative FBC (hazard ratio [HR] = 1.68), breast cancer family history (HR = 2.20), and nulliparity (HR = 1.37). In older women (FBC at age ≥50 years), higher risk was associated with breast cancer family history (HR = 1.32), premenopausal status (HR = 1.49), overweight (HR = 1.39), and higher alcohol consumption (HR = 1.34). For ISBC, higher risk was associated with married status (HR = 1.94) in younger women, and overweight (HR = 1.60) among older women. For CSBC, HR estimates were generally similar across racial and ethnic groups. Even after adjustment for these risk factors, compared with NHW women, risk remained elevated for CSBC in younger African American, Asian American, and Hispanic women, and for ISBC in older African American and Hispanic women with ER/PR-positive FBC.
Our findings support genetic risk evaluation, enhanced screening, and lifestyle changes in women at higher risk of SBC. Additional risk factors must contribute to the unequal burden of SBC across racial and ethnic groups.
关于第二原发性乳腺癌（SBC）危险因素的流行病学研究主要在非西班牙裔白人（NHW）女性中开展。
将一个基于人群的、种族和民族多样化的9639例患有第一原发性I - III期浸润性乳腺癌（FBC）的女性队列与加利福尼亚癌症登记处相链接；识别出618例对侧SBC（CSBC）和278例同侧SBC（ISBC），这些病例均在FBC诊断6个月后确诊。使用考虑竞争风险的Fine和Gray模型，我们评估了CSBC和ISBC风险与FBC临床特征及流行病学因素之间的关联。
在年轻女性（FBC发病年龄<50岁）中，较高的CSBC风险与ER/PR阴性FBC（风险比[HR]=1.68）、乳腺癌家族史（HR = 2.20）和未生育（HR = 1.37）相关。在老年女性（FBC发病年龄≥50岁）中，较高风险与乳腺癌家族史（HR = 1.32）、绝经前状态（HR = 1.49）、超重（HR = 1.39）和较高酒精摄入量（HR = 1.34）相关。对于ISBC，年轻女性中较高风险与婚姻状况（HR = 1.94）相关，老年女性中与超重（HR = 1.60）相关。对于CSBC，各种族和民族组的HR估计值总体相似。即使在对这些风险因素进行调整后，与NHW女性相比，年轻的非裔美国女性、亚裔美国女性和西班牙裔女性患CSBC的风险仍然升高，而老年非裔美国女性和患有ER/PR阳性FBC的西班牙裔女性患ISBC的风险仍然升高。
我们的研究结果支持对SBC高危女性进行遗传风险评估、加强筛查和改变生活方式。其他风险因素必定导致了SBC在不同种族和民族群体中负担不均。
