Understanding breast cancer subtypes in Black women

 描述(由申请者提供)：对于黑人女性比白人女性更容易被诊断出患有侵袭性疾病的原因，人们知之甚少。根据免疫组织化学(IHC)标志物的特征，在每个年龄段中，白人女性雌激素受体(ER)+乳腺癌的比例最高，黑人女性ER-乳腺癌的比例最高。此外，三阴性乳腺癌[TNBC；ER-，孕激素受体(PR)-，人表皮生长因子受体2(HER2)-]是基底细胞样乳腺癌的侵袭性亚型，在黑人女性中比白人女性更常见，比其他亚型预后更差。最近的研究主要在白人女性中进行，报告了与荷尔蒙相关的乳腺癌亚型和其他风险因素相关的风险差异，如月经初潮年龄、口服避孕药使用、产次、首次足月分娩年龄、母乳喂养、绝经年龄、激素替代治疗使用、肥胖和体育活动，这表明乳腺癌亚型可能有不同的病因。很少有乳腺癌研究包括大量黑人女性，尽管已知不同亚型的癌症发病率存在显著的种族差异，而且大多数研究都没有收集肿瘤组织来详细描述肿瘤亚型。 为了解决这个问题，我们建议从710例黑人乳腺癌病例中收集肿瘤组织样本，根据激素受体状态对乳腺肿瘤进行分类，并检查黑人女性中激素相关和其他危险因素与乳腺癌亚型之间的关系。乳腺癌与许多可改变的危险因素的相关性似乎因肿瘤亚型而不同；因此，在未来的研究中，对所有乳腺肿瘤进行亚型分型是必不可少的。利用即将完成的以黑人妇女为基础的人口病例对照研究是收集和分类 乳腺癌肿瘤组织，因为我们已经获得了参与者的许可。这项拟议的项目将是最全面和最有力的研究之一，以调查激素相关因素和其他风险因素与黑人女性乳腺癌亚型之间的关系。此外，肿瘤组织的收集将在不久的将来提供机会，将这些危险因素分析扩展到内在的分子亚型。这项研究的结果将填补目前关于增加黑人女性侵袭性乳腺癌风险的激素相关因素评估的一个重要空白，并将有助于确定预后较差的乳腺癌亚型的高风险(或低风险)黑人女性谁将从筛查中受益，并可能为降低黑人女性侵袭性乳腺癌的风险提供新的目标。这可能为开发针对种族和乳腺癌亚型的临床有用的乳腺癌预测模型铺平道路。

 DESCRIPTION (provided by applicant): Little is understood about what factors might explain why Black women tend to be diagnosed with more aggressive disease than White women. Based on characterization by immunohistochemical (IHC) markers, in every age group, White women have the highest rates of estrogen receptor (ER)+ breast cancer and Black women have the highest rates of ER- breast cancer. Moreover, triple negative breast cancer [TNBC; ER-, progesterone receptor (PR)-, human epidermal growth factor receptor 2 (HER2)-], an aggressive subset of basal-like breast cancer, is more common among Black women than among White women and has a worse prognosis than other subtypes. Recent studies, conducted largely among White women, have reported differences in risk by breast cancer subtype associated with hormone-related and other risk factors, such as age at menarche, oral contraceptive use, parity, age at first full-term birth, breastfeeding, age at menopause, hormone replacement therapy use, obesity and physical activity, suggesting that subtypes of breast tumors may have distinct etiologies. Few breast cancer studies have included large numbers of Black women, despite known marked racial differences in cancer incidence by subtype, and most studies did not collect tumor tissue to allow for detailed characterization of tumor subtypes. To address this issue, we propose to collect tumor tissue specimens from 710 Black breast cancer cases, to classify breast tumors by hormone-receptor status, and to examine associations between hormone-related and other risk factors and breast cancer subtypes among Black women. The association of breast cancer with many modifiable risk factors appears to differ by tumor subtype; therefore, it is essential to perform subtyping of all breast tumors in future studies. The utilization of a soon to be completed population-based case-control study of Black women is a highly efficient approach to the collection and classification of breast cancer tumor tissue since we have already obtained participants' permission. This proposed project will be one of the most comprehensive and well-powered studies to investigate the associations between hormone-related and other risk factors and breast cancer subtypes among Black women. Moreover, the collection of tumor tissue will provide immediate future opportunities to extend these risk factor analyses to intrinsic molecular subtypes. The results of this study will fill an important gap in current knowledge regarding assessment of hormone-related factors that increase risk for aggressive breast cancer among Black women, and will assist in delineating Black women at high (or low) risk for breast cancer subtypes with a poor prognosis who will most benefit from screening, and may provide new targets to reduce the risk of aggressive breast cancer among Black women. This may pave the way for the development of clinically useful breast cancer prediction models specific to race and breast cancer subtype.