Association of breast cancer and its therapies with fracture

描述(申请人提供)：骨质骨折是影响乳腺癌幸存者，特别是绝经后乳腺癌幸存者的最常见的疾病之一。有证据表明，乳腺癌患者的骨折风险大大高于普通人群，而且在未来几年可能会恶化。首先，几项欧洲研究和妇女健康倡议发现，即使在他莫昔芬是最常见的激素剂的时代，乳腺癌幸存者的骨折风险也会增加。他莫昔芬可能会对骨折提供一些保护。其次，对绝经前妇女的临床试验表明，在细胞毒性辅助化疗后，骨密度迅速下降。在绝经后女性中，证据更为有限，但动物研究和单中心人体研究表明，细胞毒性化疗也可能增加她们骨折的风险。最后，随着芳香酶抑制剂(AIs)的引入，辅助激素治疗的进展表明，骨质疏松症将成为未来更严重的问题。临床试验表明，人工智能降低了乳腺癌死亡率，但增加了约40%的骨折风险。考虑到这些因素，我们建议确定绝经后SEER-Medicare乳腺癌幸存者和年龄匹配的Medicare参与者的基于人群的样本中髋部和全非脊椎骨折的五年发生率。这项研究还将在同一样本的绝经后乳腺癌幸存者中检查含有氨甲喋呤和蒽环类药物的常见辅助化疗方案与骨折的任何关联。最后，这项研究将探索绝经后乳腺癌最常用的辅助激素疗法(他莫昔芬和芳香酶抑制剂)与绝经后乳腺癌幸存者的髋部和完全非脊椎骨折之间的关系。这项研究将提供老年乳腺癌患者骨质疏松性骨折发生的有效性数据，以及它们与最初的系统辅助治疗的关系。它将为乳腺癌幸存者中骨质疏松的咨询和治疗计划提供重要的指导。它从早期芳香酶抑制剂使用者的人群队列中的初步发现应该为未来使用Medicare Part D或其他管理数据对各种激素疗法的长期骨骼影响的研究提供重要的先导数据。公共卫生相关性：骨折是影响乳腺癌幸存者，特别是绝经后乳腺癌幸存者的最常见问题之一。我们将调查绝经后乳腺癌幸存者与非乳腺癌女性的骨折风险，然后探索乳腺癌治疗(化疗或芳香酶抑制剂)对骨折风险的贡献。这项研究应该为乳腺癌幸存者的骨质疏松症的咨询和治疗提供重要的指导。

DESCRIPTION (provided by applicant): Bony fractures are among the most common morbidities affecting breast cancer survivors, particularly postmenopausal breast cancer survivors. There is evidence to suggest that the fracture risk for breast cancer patients is substantially higher than the general population, and that it is likely to worsen in coming years. First, several European studies and the Women's Health Initiative identified an increased fracture risk among breast cancer survivors even in the era when tamoxifen, which may offer some protection against fractures, was the most common hormonal agent. Second, clinical trials in premenopausal women have shown rapid losses in bone density after cytotoxic adjuvant chemotherapy. Evidence is more limited among postmenopausal women, but animal studies and single-center human studies suggest that cytotoxic chemotherapy might also increase their fracture risk. Finally, advances in adjuvant hormonal therapy with the introduction of aromatase inhibitors (AIs) suggest that osteoporosis will become a greater problem in the future. Clinical trials suggest that AIs reduce breast cancer mortality but increase fracture risk by approximately 40%. Given these considerations, we propose to determine the five-year incidence of hip and total nonvertebral fractures among a population-based sample of postmenopausal SEER-Medicare breast cancer survivors compared with age-matched Medicare enrollees. The study will also examine any association of common adjuvant chemotherapy regimens containing methotrexate and anthracyclines with fractures among the same sample of postmenopausal breast cancer survivors. Finally, this study will explore the association of the most commonly used adjuvant hormonal therapies for postmenopausal breast cancer (tamoxifen and aromatase inhibitors) with hip and total nonvertebral fractures among a population-based surveyed cohort of postmenopausal breast cancer survivors. This study will provide effectiveness data regarding the occurrence of osteoporotic fractures in older breast cancer patients and their relationship to initial systemic adjuvant therapies. It will provide important guidance for counseling and treatment initiatives for osteoporosis among breast cancer survivors. Its preliminary findings from a population-based cohort of early aromatase inhibitor users should provide important pilot data for future study into longer-term bone effects of various types of hormonal therapies using Medicare Part D or other administrative data. PUBLIC HEALTH RELEVANCE: Bony fractures are among the most common problems affecting breast cancer survivors, particularly postmenopausal breast cancer survivors. We will investigate the risk of fracture among postmenopausal breast cancer survivors compared with women without breast cancer, and then will explore the contribution of breast cancer treatments (chemotherapy or aromatase inhibitors) to fracture risk. This study should provide importance guidance for counseling and treatment initiatives for osteoporosis among breast cancer survivors.