Althuis Michelle D, Fergenbaum Jennifer H, Garcia-Closas Montserrat, Brinton Louise A, Madigan M Patricia, Sherman Mark E
Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Room 7084, 6120 Executive Boulevard, Rockville, MD 20852, USA.
Cancer Epidemiol Biomarkers Prev. 2004 Oct;13(10):1558-68.
Breast cancers classified by estrogen receptor (ER) and/or progesterone receptor (PR) expression have different clinical, pathologic, and molecular features. We examined existing evidence from the epidemiologic literature as to whether breast cancers stratified by hormone receptor status are also etiologically distinct diseases. Despite limited statistical power and nonstandardized receptor assays, in aggregate, the critically evaluated studies (n = 31) suggest that the etiology of hormone receptor-defined breast cancers may be heterogeneous. Reproduction-related exposures tended to be associated with increased risk of ER-positive but not ER-negative tumors. Nulliparity and delayed childbearing were more consistently associated with increased cancer risk for ER-positive than ER-negative tumors, and early menarche was more consistently associated with ER-positive/PR-positive than ER-negative/PR-negative tumors. Postmenopausal obesity was also more consistently associated with increased risk of hormone receptor-positive than hormone receptor-negative tumors, possibly reflecting increased estrogen synthesis in adipose stores and greater bioavailability. Published data are insufficient to suggest that exogenous estrogen use (oral contraceptives or hormone replacement therapy) increase risk of hormone-sensitive tumors. Risks associated with breast-feeding, alcohol consumption, cigarette smoking, family history of breast cancer, or premenopausal obesity did not differ by receptor status. Large population-based studies of determinants of hormone receptor-defined breast cancers defined using state-of-the-art quantitative immunostaining methods are needed to clarify the role of ER/PR expression in breast cancer etiology.
根据雌激素受体（ER）和/或孕激素受体（PR）表达分类的乳腺癌具有不同的临床、病理和分子特征。我们研究了流行病学文献中的现有证据，以确定按激素受体状态分层的乳腺癌在病因上是否也是不同的疾病。尽管统计效力有限且受体检测方法不标准，但综合来看，经过严格评估的研究（n = 31）表明，激素受体定义的乳腺癌病因可能是异质性的。与生殖相关的暴露往往与ER阳性肿瘤而非ER阴性肿瘤的风险增加有关。未生育和生育延迟与ER阳性肿瘤的癌症风险增加比与ER阴性肿瘤的关联更为一致，初潮早与ER阳性/PR阳性肿瘤比与ER阴性/PR阴性肿瘤的关联更为一致。绝经后肥胖与激素受体阳性肿瘤风险增加的关联也比与激素受体阴性肿瘤更为一致，这可能反映了脂肪组织中雌激素合成增加和更高的生物利用度。已发表的数据不足以表明使用外源性雌激素（口服避孕药或激素替代疗法）会增加激素敏感性肿瘤的风险。与母乳喂养、饮酒、吸烟、乳腺癌家族史或绝经前肥胖相关的风险在受体状态方面没有差异。需要开展基于人群的大型研究，采用最先进的定量免疫染色方法来确定激素受体定义的乳腺癌的决定因素，以阐明ER/PR表达在乳腺癌病因中的作用。
