RISK FACTORS FOR TRIPLE-NEGATIVE AND HER2-OVEREXPRESSING BREAST CANCER AMONG HI..

摘要： 三阴性（TN）（不表达雌激素受体（ER）、孕激素受体（PR）或HER 2的肿瘤）和HER 2过表达（H2 E）（ER-/HER 2+的肿瘤）乳腺癌是两种特别侵袭性的乳腺癌分子亚型，对西班牙裔女性和其他医学弱势群体的影响不成比例。然而，影响其病因和疾病的因素在很大程度上是未知的，并且评估这些问题的少数研究中没有一项包括有意义数量的西班牙裔病例。为了解决这一现有的研究差距，我们提出了一个基于人口的病例-病例研究乳腺癌的妇女年龄在20-69岁的西雅图，华盛顿和阿尔伯克基，新墨西哥州大都市区。本研究将纳入1120例TN、600例H2 E和1120例管腔（ER+）浸润性乳腺癌病例，其中包括175例TN、90例H2 E和175例西班牙裔管腔病例。将进行详细的医疗记录审查，以确定许多乳腺癌风险因素的数据。样本量为 本研究的规模远大于其他任何已发表的关于这些肿瘤类型的研究，重点关注这些肿瘤最常见的年龄范围，并纳入了大量西班牙裔病例，因此，本研究将使我们能够解决以下新问题： 1.如何确定乳腺癌的危险因素，包括生殖因素，人体测量 测量、乳房X线摄影密度和乳腺癌家族史与TN风险相关， H2 E乳腺癌相对于管腔乳腺癌的风险？几项样本量有限的研究表明，TN、H2 E和管腔型乳腺癌具有不同的危险因素特征，但这些结果需要在更大的人群基础上进行确认。考虑到大多数乳腺癌风险因素会增加乳腺癌的风险，而与种族/民族无关，识别TN和H2 E特异性风险因素可能具有广泛的公共卫生重要性，并为西班牙裔和非洲裔美国人经历的这两种侵袭性类型乳腺癌的较高发病率提供重要的见解。 2.确定的危险因素与TN和H2 E乳腺癌风险之间的关联是否不同 在西班牙裔和非西班牙裔之间？虽然大多数风险因素不太可能通过西班牙裔种族与TN和H2 E的相关性发生变化，但有一些数据表明，有些风险因素，如家族史，可能会影响到我们的研究。我们的研究的优势是在将女性定义为西班牙裔时纳入遗传祖先。 3.乳腺癌危险因素如何影响确诊妇女的死亡风险 TN和H2 E乳腺癌的患者吗一些流行病学风险因素，特别是肥胖，影响乳腺癌幸存者的死亡风险。然而，之前没有研究评估这些风险因素如何对TN和H2 E乳腺癌幸存者的死亡风险产生差异影响。

Abstract: Triple-negafive (TN) (tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or HER2) and HER2-overexpressing (H2E) (tumors that are ER-/HER2+) breast cancers are two particularly aggressive molecular subtypes of breast cancer that disproportionately impact Hispanic women and other medically disadvantaged populations. However, factors influencing their etiologies and prognoses are largely unknown, and none of the few studies assessing these questions have included a meaningful number of Hispanic cases. To address this existing research gap, we propose a population-based case-case study of breast cancer among women aged 20-69 years in the Seattle, Washington and Albuquerque, New Mexico greater metropolitan areas. This study will include 1120 TN, 600 H2E, and 1120 luminal (ER+) invasive breast cancer cases, including 175 TN, 90 H2E, and 175 luminal cases that are Hispanic. Detailed medical record reviews will be conducted to ascertain data on numerous breast cancer risk factors. With a sample size that is substantially larger than any other published study of these tumor types, a focus on the age range over which these tumors are most common, and inclusion of a substanfial number of Hispanic cases, this study will enable us to address the following new quesfions: 1. How are established breast cancer risk factors, including reproductive factors, anthropometric measures, mammographic density, and family history of breast cancer, related to risks of TN and H2E breast cancer relative to risk of luminal breast cancer? Several studies with limited sample sizes indicate that TN, H2E and luminal breast cancers have different risk factor proflles, but these results require confirmation in a larger population-based setfing. Given that most breast cancer risk factors confer elevated risks of breast cancer independent of race/ethnicity, identifying TN and H2E specific risk factors could have broad public health importance and provide important insight Into the contributors to the higher incidence rates of these two aggressive types of breast cancer that both Hispanics and African Americans experience. 2. Do the associations between established risk factors and risks of TN and H2E breast cancer differ among Hispanics and non-Hispanics? While most risk factors are unlikely to difl'er in their associafion with TN and H2E by Hispanic ethinicity, there is some data to suggest that some, like family history, might A strength of our study is the incorporation of genetic ancestry when defining women as Hispanic. 3. How do established breast cancer risk factors influence risk of mortality among women diagnosed with TN and H2E breast cancers? Several epidemiologic risk factors, notably obesity, influence risk of mortality among breast cancer survivors. However, no prior studies have assessed how such risk factors may differentially impact risk of mortality among TN and H2E breast cancer survivors.