A PHASE III RANDOMIZED STUDY OF EXEMESTANE PLUS PLACEBO VERSUS EXEMESTANE PLU

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。乳腺癌是西方女性最常见的恶性肿瘤。他莫昔芬是一种常用来治疗乳腺癌的药物，它可以阻断雌激素对乳房和其他组织的作用。在随机试验中，他莫昔芬通过降低乳腺癌高风险妇女的乳腺癌风险，为乳腺癌化学预防建立了“原理证明”。然而，他莫昔芬罕见但危及生命的副作用，包括子宫内膜癌、肺部和腿部血栓以及中风，严重限制了他莫昔芬用于降低风险的普遍使用。这类芳香酶抑制剂通过降低雌激素水平来治疗绝经后妇女的乳腺癌，与子宫内膜癌、血栓或中风的增加无关。当这类药物被发现可以降低绝经后乳腺癌切除术妇女患对侧乳腺癌的新风险时，人们对它们在降低乳腺癌风险方面的潜在用途产生了兴趣。塞来昔布是一种非类固醇抗炎剂（NSAID）处方剂，用于治疗疼痛和炎症。临床前和观察性研究表明，这些药物在降低乳腺癌风险方面也有潜在作用。目前的研究将评估依西美坦单独使用或与塞来昔布联合使用是否可以降低乳腺癌的风险，并且在其他健康的绝经后妇女中，基于她们的年龄或乳房x光检查乳房密度，乳腺癌的风险增加。进入的女性必须是绝经后的女性，并且根据计算的Gail风险评分，包括家庭和生育史，年龄60岁或以上，之前的某个夜间乳房活检结果，乳腺癌风险增加。同时使用非甾体抗炎药的妇女和最近使用更年期激素治疗或SERM的妇女不符合条件。参与者将在基线进行病史和体格检查，血液检查和最近的乳房x光检查和骨密度检查（DEXA）。将收集生活质量问卷和其他药物信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Breast cancer is the most common malignancy in Western women. Tamoxifen is an agent commonly used to treat breast cancer which blocks some of estogen's actions on the breast and other tissues. In randomized trials, tamoxifen has established "proof of principle" for breast cancer chemoprevention by reducing breast cancer risk in women at increased risk of breast cancer. However, rare but life-threatening side effects of tamoxifen, including endometrial cancer, blood clots in lungs and legs and stroke have severely limited general use of tamoxifen for risk reduction. The class of aromatase inhibitors are used to treat breast cancer in postmenopausal women by reducing estrogen levels and are not associated with increased endometrial cancer, blood clots or strokes. When agents in this class were found to reduce risk of new contralatral breast cancer in postmenopausal women with resected breast cancer, interest in their potential use for breast cancer risk reduction developed. Celecoxib is a non-steroid anti-inflammatory agent (NSAID) prescription agent used to treat pain and inflammatory condition. Preclinical and observational studies now suggest a potential role for breast cancer risk reduction of these agents as well. The current study will evaluate whether exemestane either alone or together with celecoxib can reduce the risk of breast cancer with a favorable risk to benefit ratio in otherwise healthy postmenopausal women at increased risk for developing breast cancer based on their age or mammogram breast density. For entry, women must be postmenopausal and be at increased breast cancer risk based on a calculated Gail risk score incorporating family and reproductive history, age 60 years or greater, a certain prior benight breast biopsy results. Women with concurrent NSAID use and those with recent menopausal hormone therapy or SERM use are not eligible. Participants will have a history and physical exam at baseline, blood tests and recent prior mammogram and bone density test (DEXA). A quality of life questionnaire and information on other medication will be collected.