Fractures, Heart Disease, and Stroke on Aromatase Inhibitors

描述(申请人提供)：乳腺癌是女性中最常见的癌症，也是癌症相关死亡的第二大原因。然而，大多数患有乳腺癌的女性被诊断为早期疾病，她们死于癌症的风险低于她们死于其他原因的风险。由于这些女性的预后如此之好，治疗的选择尤为重要，因为治疗的副作用和并发症对整体健康状况的影响可能比乳腺癌本身更大。最近，确认芳香酶抑制剂对早期癌症有实质性好处的随机对照试验导致了全国性的建议，即每一位患有雌激素受体阳性且没有禁忌症的绝经后女性，在她的辅助疗程的某个时候，都应该使用芳香酶抑制剂进行治疗。然而，这些药物可能会产生不良影响。临床试验已经确认了骨折发生率的增加，一些研究表明，与服用他莫昔芬或安慰剂的女性相比，服用芳香酶抑制剂的患者的非乳腺癌死亡人数没有显著增加，这表明这些药物可能会影响其他原因的死亡风险，如心血管疾病。利用WellPoint公司的独立子公司HealthCore的管理数据，我们将探索在51岁早期乳腺癌患者的社区人群中使用芳香酶抑制剂是否与心血管事件和骨折发生率的增加有关。此外，我们还将检查接受芳香酶抑制剂治疗的女性是否正在接受推荐的骨密度测试。对照组将包括只接受他莫昔芬治疗的乳腺癌妇女，随后接受芳香酶抑制剂治疗的他莫昔芬，不接受激素治疗的妇女，以及没有乳腺癌病史的密切匹配的妇女。具体地说，我们将：1.评估芳香酶抑制剂治疗是否与临床试验以外的心肌梗死、中风和骨折风险增加有关。2.确定在接受芳香酶抑制剂治疗期间或多或少有患心血管疾病和骨折风险的女性亚组。3.评估正在接受芳香酶抑制剂治疗的女性是否正在接受推荐的骨密度测试。项目简介/相关性：芳香酶抑制剂目前被广泛用作乳腺癌的辅助治疗，更好地了解与这种疗法相关的潜在风险以及这些风险如何因患者特征而不同，将有助于医生和患者在做出使用该疗法的决定时权衡潜在的好处和风险。此外，有关这种疗法潜在危害的信息可能会导致降低接受芳香酶抑制剂治疗的女性的风险和非癌症死亡率的策略。公共卫生相关性：最后，了解接受芳香酶抑制剂治疗的女性是否正在接受推荐的骨密度测试，将有助于确定是否需要新的策略来改进测试，以确定药物导致的骨丢失。

DESCRIPTION (provided by applicant): Breast cancer is the most commonly diagnosed cancer among women and the second leading cause of cancer related deaths. Nevertheless, most women with breast cancer are diagnosed with early-stage disease, and their risk of dying of cancer is lower than their risk of dying of other causes. Because prognosis for these women is so good, the choices of treatments are particularly important, because side effects and complications of treatments may impact overall health status more than the breast cancer itself. Recently, randomized controlled trials identifying substantial benefits of aromatase inhibitors for early- stage cancers have led to national recommendations that every postmenopausal woman with an estrogen receptor-positive breast cancer and no contraindications be treated with an aromatase inhibitor at some point in her adjuvant course. Nevertheless, these drugs may have adverse effects. Clinical trials have identified increases in fracture rates, and some studies have demonstrated a non-significant increase in non-breast cancer deaths in patients taking aromatase inhibitors compared to women on tamoxifen or placebo, suggesting that the drugs may impact the risk of death from other causes, such as cardiovascular disease. Using administrative data from HealthCore, an independent subsidiary of WellPoint, Inc, we will explore whether the use of aromatase inhibitors in community-based populations of early-stage breast cancer patients aged 51 is associated with an increased incidence of cardiovascular events and fracture. In addition, we will examine whether women treated with aromatase inhibitors are receiving recommended bone density testing. Comparison groups will include women with breast cancer treated with tamoxifen only, tamoxifen followed by aromatase inhibitors, no hormonal therapy, and closely-matched women with no history of breast cancer. Specifically, we will: 1. Assess whether aromatase inhibitor therapy is associated with increased risk of myocardial infarction, stroke, and fracture outside of the clinical trial setting. 2. Identify subgroups of women who have more or less favorable risk of cardiovascular disease and fracture while on aromatase inhibitor therapy. 3. Assess whether women who are being treated with aromatase inhibitors are receiving recommended bone density testing. Project Narrative/Relevance: Aromatase inhibitors are currently being used widely as an adjuvant treatment for breast cancer, and understanding better the potential risks associated with this therapy and how these risks differ by patient characteristics will help physicians and patients weigh potential benefits and risks when decisions about use of this therapy are being made. In addition, information about potential harms of this therapy may lead to strategies to reduce risk and decrease non-cancer mortality for women who are treated with aromatase inhibitors. PUBLIC HEALTH RELEVANCE: Finally, understanding whether women treated with aromatase inhibitors are receiving recommended bone density testing will help identify whether new strategies are needed to improve testing to identify drug-induced bone loss.