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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 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于治疗乳腺癌的药物，它可以阻断雌激素对乳腺和其他组织的作用。 在随机试验中，他莫昔芬通过降低乳腺癌风险增加的妇女的乳腺癌风险，建立了乳腺癌化学预防的“原则证据”。然而，他莫昔芬的罕见但危及生命的副作用，包括子宫内膜癌，肺和腿中的血栓和中风，严重限制了他莫昔芬用于降低风险的一般用途。 芳香酶抑制剂类用于治疗绝经后妇女的乳腺癌，通过降低雌激素水平，并没有增加子宫内膜癌，血栓或中风。当发现这类药物可降低绝经后乳腺癌切除术后女性新发对侧乳腺癌的风险时，人们对其用于降低乳腺癌风险的潜在用途产生了兴趣。塞来昔布是一种用于治疗疼痛和炎症的非类固醇抗炎药（NSAID）处方药。临床前和观察性研究现在表明，这些药物在降低乳腺癌风险方面也具有潜在作用。 目前的研究将评估依西美坦单独或与塞来昔布联合使用是否可以降低乳腺癌的风险，并在其他方面健康的绝经后女性中具有有利的风险获益比，这些女性根据其年龄或乳房X线摄影乳腺密度发生乳腺癌的风险增加。对于进入，女性必须是绝经后，并根据计算的Gail风险评分（包括家族史和生殖史），年龄60岁或以上，一定的既往乳腺活检结果，乳腺癌风险增加。同时使用NSAID的妇女和最近接受绝经激素治疗或使用SERM的妇女不符合条件。参与者将在基线时进行病史和体格检查，血液检查和最近的乳房X线检查和骨密度检查（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 estrogen'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.