HRT USE AND RISK OF LOBULAR AND DUCTAL BREAST CANCER

描述（改编自申请人的摘要）： 发病率 浸润性小叶乳腺癌（ILBC）在美国稳步增加 自 1977 年以来，导管乳腺发病率呈增加趋势 自 1987 年以来，癌症发病率已趋于稳定。小叶肿瘤的数量有所增加 特别是 50 岁以上的女性。 联合使用雌激素-孕激素 激素替代疗法（CHRT）在此期间也稳步上升 期间，两项病例对照调查的最新分析表明 使用 CHRT 的绝经后女性可能会增加 ILBC 的风险，而 CHRT 与导管癌没有关系。流行病学研究很少 评估了已知或怀疑的乳腺癌危险因素有何不同 跨越不同的组织学类型，但这样的研究很重要 因为可能有多种途径导致发展和 不同组织学类型的乳腺癌的进展。 这项拟议研究的主要目的是确认最近的初步结果 研究结果显示，在很多情况下，CHRT 与小叶乳腺癌相关 基于人群的研究，更详细地评估这种关系，并 探索该协会的机制。 我们建议对 900 名 55-79 岁的女性进行病例对照研究。 被诊断患有乳腺癌（450 小叶癌，450 导管癌）和 450 居住在西雅图-普吉特湾三个县的人口控制 华盛顿西部都会区。需要解决的具体问题 是： (1) CHRT 的使用与以下疾病发生率的增加有关： 55-79 岁女性的浸润性小叶乳腺癌。 (2)是否使用CHRT 与浸润性导管乳腺癌发病率增加有关 55-79岁的女性？ (3) CHRT 使用的持续时间、模式和/或新近度 影响协会的规模？ (4) CHRT 的使用是否与 组织学特征、肿瘤细胞增殖的改变，或 类固醇激素受体、癌基因、细胞周期和细胞的表达 小叶和导管乳腺癌的死亡调节蛋白？

DESCRIPTION (Adapted from the Applicant's Abstract): Incidence rates of invasive lobular breast carcinomas (ILBC) have increased steadily in the United States since 1977, whereas the trend of increasing incidence of ductal breast cancer has plateaued since 1987. This rise in lobular tumors has occurred specifically among women over age 50. The use of combined estrogen-progestin hormone replacement therapy (CHRT) has also risen steadily over this time period, and recent analyses from two case-control investigations suggest that postmenopausal women who use CHRT may have an increased risk of ILBC, whereas there is no relationship of CHRT to ductal cancer. Few epidemiologic studies have assessed how known or suspected risk factors for breast cancer differ across different histologic types, but such investigations are important because there are likely to be multiple pathways leading to the development and progression of breast cancer of different histologic types. The primary objectives of this proposed study are to confirm recent preliminary findings that CHRT is associated with lobular breast cancer in a large population-based study, to assess this relationship in greater detail, and to explore mechanisms for this association. We propose to conduct a case-control study of 900 women aged 55-79 who have been diagnosed with breast cancer (450 lobular, 450 ductal) and 450 population-based controls who reside in the three county Seattle-Puget Sound metropolitan area of western Washington. The specific questions to be addressed are: (1) Is the use of CHRT associated with an increase in the incidence of invasive lobular breast cancer in women aged 55-79. (2) Is the use of CHRT associated with an increase in the incidence of invasive ductal breast cancer in women aged 55-79? (3) Do the duration, patterns and/or recency of CHRT use influence he size of the association? (4) Is the use of CHRT associated with alteration in the histologic characteristics, tumor cell proliferation, or expression of steroid hormone receptors, oncogenes, and cell cycle and cell death regulator proteins of lobular and ductal breast cancers?