HRT USE AND RISK OF LOBULAR AND DUCTAL BREAST CANCER

描述（改编自申请人摘要）： 浸润性小叶乳腺癌（ILBC）在美国 自1977年以来，美国乳腺癌的发病率呈上升趋势， 癌症自1987年以来一直处于稳定状态。这种小叶肿瘤的增加发生在 尤其是50岁以上的女性。联合雌激素-孕激素的应用 激素替代疗法（CHRT）也在这段时间稳步上升 期间，最近两项病例对照调查的分析表明， 使用CHRT的绝经后妇女可能会增加ILBC的风险，而 CHRT与导管癌无关。很少有流行病学研究 已经评估了已知或疑似乳腺癌风险因素的差异 在不同的组织学类型，但这样的调查是重要的 因为可能有多种途径导致发展， 不同组织学类型乳腺癌的进展。 这项拟议研究的主要目标是确认最近的初步 研究发现，CHRT与小叶乳腺癌在一个大的 基于人口的研究，以更详细地评估这种关系，并 探索这种联系的机制。 我们建议对900名年龄在55-79岁之间的妇女进行病例对照研究， 被诊断患有乳腺癌（450小叶，450导管）和450 居住在西雅图-普吉特湾三个县的基于人口的对照组 美国华盛顿西部的一个大都市区。需要解决的具体问题 （1）CHRT的使用是否与以下事件的发生率增加有关： 55-79岁女性浸润性小叶乳腺癌。(2)使用CHRT 与浸润性导管乳腺癌发病率的增加有关 在55-79岁的女性中？(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 组织学特征改变、肿瘤细胞增殖或 类固醇激素受体、癌基因、细胞周期和细胞 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?