A pooled analysis for risk factors of triple negative breast cancer

描述（由申请人提供）：三阴性乳腺癌（TNBC）是雌激素受体（ER）、孕酮受体（PR）和人表皮生长因子受体-2（HER 2）阴性的乳腺肿瘤亚型。由于其侵袭性和缺乏有效的靶向治疗，TNBC患者的预后通常比最常见的乳腺癌亚型管腔A（ER+或PR+，HER 2-）患者更差。TNBC患者的总体5年生存率比管腔A患者低至少10%。此外，TNBC往往比其他人更频繁地袭击绝经前黑人妇女。我们的长期目标是更好地了解TNBC的病因，以便我们可以开发有针对性的方法，减少其在全人群范围内的发生。基因表达研究表明管腔A肿瘤与ER信号传导相关，而大多数TNBC的特征在于“基底样”分子谱，通常过表达参与细胞增殖和分化的基因。基于临床和分子差异 在TNBC和管腔A之间，我们假设这两种亚型的风险特征可能不同。先前的研究表明，乳腺癌的既定风险因素（例如，生殖因素）与鲁米那A有关。然而，由于在大多数已发表的单一研究中TNBC病例数量较少，以及可用于已发表的合作或协作研究的风险因素数据有限，因此TNBC风险状况仍然模糊。 合并分析。本提案的目的是确定TNBC的风险因素，比较其对发生TNBC和管腔A的可能性的贡献，并确定人种或绝经状态是否改变TNBC的任何总体主效应或TNBC和管腔A之间检测到的任何异质性。我们有机会获得现有的数据收集的三个大型人口为基础的病例对照研究的妇女年龄在20-64岁。数据包括病例参与者的ER/PR/HER 2状态以及关于病例和对照参与者的各种暴露的详细信息。这些研究将为我们提供大量的TNBC病例（n=566）和扩展的风险因素列表的详细信息，这在大多数以前的研究中是不可用的。感兴趣的因素是10个已知的和可疑的风险或保护因素时，乳腺癌被认为是一种单一的疾病。这些因素包括月经/生殖史、口服避孕药使用、绝经期激素治疗使用、体型测量及其随时间的变化、种族、乳腺癌家族史、娱乐性体育活动、饮酒、吸烟和产前因素。TNBC病例的大样本、潜在乳腺癌风险因素的扩展列表以及研究参与者在种族（白色、黑色）和年龄（绝经前和绝经后）方面的多样性，都提供了进行本研究所需的资源。该项目的成功完成将为TNBC的病因学提供新的见解，这可能导致在全人群范围内预防TNBC的新的靶向方法。

DESCRIPTION (provided by applicant): Triple negative breast cancer (TNBC) is the breast tumor subtype that is negative for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Due to its aggressive nature and the lack of effective targeted therapies, patients with TNBC generally have a poorer prognosis than patients with the most common breast cancer subtype, luminal A (ER+ or PR+, HER2-). The overall 5-year survival rate for TNBC patients is at least 10% lower than that for luminal A patients. Furthermore, TNBC tends to strike premenopausal black women more frequently than others. Our long-term goal is to better understand the etiology of TNBC so that we can develop targeted approaches that reduce its occurrence on a population-wide scale. Gene expression studies indicate luminal A tumors are associated with ER signaling, whereas the majority of TNBCs are characterized by a "basal-like" molecular profile, typically overexpressing genes involved in cell proliferation and differentiation. Based on the clinical and molecular differences between TNBC and luminal A, we hypothesize that the risk profiles for these two subtypes are likely to be different. Previous studies have shown that established hormone-related risk factors for breast cancer overall (e.g., reproductive factors) are associated with luminal A. However, the TNBC risk profile remains vague due to the small number of TNBC cases in the majority of published single studies, and the limited risk factor data available for published collaborative or pooled analyses. The objective of this proposal is to identify risk factors for TNBC, compare their contributions to the likelihood of developing TNBC and luminal A, and determines if race or menopausal status modifies any overall main effect for TNBC or any heterogeneity detected between TNBC and luminal A. We have access to existing data collected by three large population-based case-control studies of women aged 20-64 years. The data include case participants' ER/PR/HER2 status and detailed information about various exposures for case and control participants. These studies will supply us with both a large number of TNBC cases (n=566) and detailed information for an extended list of risk factors, which are not available in most previous studies. Factors of interest are 10 known and suspected risk or protective factors identified when breast cancer was considered as a single disease. They include menstrual/reproductive history, oral contraceptive use, menopausal hormone therapy use, body size measures and their changes over time, race, breast cancer family history, recreational physical activity, alcohol consumption, cigarette smoking, and prenatal factors. The large sample of TNBC cases, the extended list of potential breast cancer risk factors, and the variety of study participants with respect to race (white, black) and age (pre- and post-menopausal), all provide the resources needed to carry out this study. Successful completion of this project will provide new insight into the etiology of TNBC, which could lead to novel targeted approaches to the prevention of TNBC on a population-wide scale.