Reproduction, Lactation and Hormonal Factors in Breast Cancer Subtypes

越来越清楚的是，乳腺癌不是单一的疾病实体，而是多种疾病的组合 不同的疾病亚型，具有不同的临床结果和病因风险因素。年的美国妇女 非洲血统(AA)在所有年龄段都有较高的乳腺癌死亡率，被诊断出来的频率更高 而且比欧洲血统的女性(EA)有更多的侵袭性肿瘤。原因是 这些种族差异尚不清楚，现有的对再生障碍性贫血女性的研究缺乏统计能力来进行调查 乳腺癌的危险因素由早期发病年龄和肿瘤生物学定义。我们正在进行的研究已经 提供了关于产次和哺乳与ER-/PR-乳腺癌风险和 基底细胞样乳腺癌。高胎次似乎与ER-样和基底样样的风险显著增加有关 年轻女性中的乳腺癌，哺乳消除了大部分多余的风险。也有证据表明 口服避孕药的使用可能是ER-乳腺癌的一个比ER+癌症更强的风险因素。AA 女性月经初潮年龄较早，母乳喂养婴儿的可能性较小，而且更有可能 她们的孩子比EA女性的年龄还小。我们建议将数据、生物标本和专业知识结合起来 来自四项关于AA女性乳腺癌的最大研究：黑人妇女健康研究， 卡罗莱纳乳腺癌研究、妇女健康圈研究和多种族队列研究。我们会 有超过6,671例AA乳腺癌病例，其中5,534例有DNA，4475例有肿瘤块。我们会 通过固有的亚型确定乳腺肿瘤的特征，然后评估生殖和激素因素 与每个亚型风险的关系，包括ER-/PR-、五种固有亚型和早发性乳腺癌 (45岁之前)。使用这四项研究的DNA样本，我们将在基因中对tag SNPs进行分型 类固醇激素途径，并评估它们与乳腺癌亚型的关系。然后我们将评估 这些遗传和生殖因素如何相互作用增加早发、ER和基底样乳房的风险 再生障碍性贫血妇女的癌症。我们还将评估与项目1、3和4中发现的遗传标记的相互作用 探讨免疫/炎症途径在早期侵袭性乳腺癌中的作用。如果我们确认 初步研究结果表明，母乳喂养可使再生障碍性贫血患者的基底样癌风险增加两倍 对于女性，我们的研究结果将对促进AA中的母乳喂养产生直接的公共健康影响 女人。

It has become increasingly clear that breast cancer is not a single disease entity, but a combination of distinct disease subtypes, with separate clinical outcomes and etiologic risk factors. American women of African ancestry (AA) have a higher mortality from breast cancer at all ages, are diagnosed more frequently at young ages, and have more aggressive tumors than women of European ancestry (EA). The reasons for these racial disparities are unclear, and existing studies of AA women lack the statistical power to investigate risk factors for breast cancer defined by early age at onset and tumor biology. Our ongoing studies have provided intriguing data regarding the relation of parity and lactation to risk of ER-/PR- breast cancer and to basal-like breast cancer. High parity appears to be associated with a strong increased risk of ER- and basal-like breast cancer in young women, with lactation removing most of the excess risk. There is also evidence that oral contraceptive use may be a stronger risk factor for ER- breast cancer than for ER+ cancer. AA women have an earlier age at menarche, are less likely to breastfeed their babies, and more likely to have their babies at a young age than are EA women. We propose to combine data, biospecimens, and expertise from four of the largest studies of breast cancer in AA women: the Black Women's Health Study, the Carolina Breast Cancer Study, the Women's Circle of Health Study, and the Multi-Ethnic Cohort. We will have over 6,671 AA breast cancer cases, with DNA available on 5,534 and tumor blocks on 4475. We will characterize breast tumors by intrinsic subtypes and then assess reproductive and hormonal factors in relation to risk of each subtype, including ER-/PR-, five intrinsic subtypes, and early onset breast cancer (before age 45). Using DNA samples from the four studies, we will genotype tagSNPs in genes in the steroid hormone pathway and assess their association with breast cancer subtypes. We will then assess how these genetic and reproductive factors interact to increase risk of early-onset, ER-, and basal-like breast cancer in AA women. We will also assess interactions with genetic markers found in Projects 1, 3, and 4 and explore the role of immune/inflammatory pathways in early aggressive breast cancer. If we confirm preliminary results that breastfeeding prevents the two-fold increase in risk of basal-like breast cancer in AA women, our results will have immediate public health impact for promotion of breastfeeding among AA women.