Clinical breast cancer risk prediction models for women with a high-risk benign breast diagnosis

项目总结/摘要 在美国，每年有超过170万例空芯针乳腺活检， 可触及肿块或乳房成像上的可疑发现。1其中75%的患者诊断为良性乳腺疾病。 活检2，包括一系列诊断，从正常或非增殖性变化， 增生性改变，有或无非典型特征。早期的研究表明，约10-30%的女性 特定的良性乳腺疾病诊断（称为“高危病变”）在手术中发现了癌症， 切除病变（称为“升级”）。3，4因此， 对于这些高危病变来说，排除恶性肿瘤是很常见的。1然而， 高风险病变的手术，其中大多数在切除时不会产生恶性诊断。 机构研究已经确定了与心脏病风险相关的各种患者、病理学和放射学变量， 女性生殖器切割升级，但没有足够的证据告知循证指南， 高危病变的患者可以安全地避免切除。5 -7长期乳腺癌的治疗也不确定。 癌症风险以及需要加强未接受癌症治疗的妇女的预防和检测战略 8 -10我们的目标是提供明确的新证据， 高危乳腺病变的临床管理建议。我们建议进行全面研究 利用乳腺癌监测联盟丰富的基础设施和纵向数据， 美国乳腺成像和病理学注册联盟。我们将补充现有的BCSC数据库， 从乳腺成像报告、病理报告和其他临床病历中新收集的数据， 自2010年以来，在100多家医疗机构诊断出7，000例高危病变。使用一个集合 学习方法，我们将开发和验证预测模型的风险升级切除（目标1）和5- 根据患者、病理学和组织病理学， 放射学因素在目标3中，我们将使用一个决策分析框架， 从利益攸关方的角度评价基于风险的战略的潜在人口影响和可接受性 用于管理高危病变。我们的研究结果将有助于识别具有可接受的低风险的女性。 对可以通过影像监测安全管理的妇女进行手术切除升级， 需要加强长期影像监测和/或化学预防的未来癌症诊断风险。 拟议的研究将比任何研究都更大，更能代表美国的临床实践 迄今为止进行的，并将是第一个全面评估病人，活检，病理和放射学 多中心研究中与高风险病变结局相关的因素。本研究产生的证据将 为空芯针活检诊断的高危病变的管理提供临床建议， 从而改善了护理，减少了美国每年诊断的> 100，000名妇女的伤害。

PROJECT SUMMARY/ABSTRACT Over 1.7 million core needle breast biopsies are performed in the U.S. every year among women with either a palpable mass or a suspicious finding on breast imaging.1 Benign breast disease is diagnosed in 75% of these biopsies2 and comprises a spectrum of diagnoses ranging from normal or non-proliferative changes to proliferative changes with or without atypical features. Early studies demonstrated that ~10-30% of women with specific benign breast disease diagnoses (referred to as “high-risk lesions”) had cancer identified on surgical excision of their lesion (referred to as “upgrade”).3,4 Thus, aggressive management with surgical excision is common for these high-risk lesions to rule out malignancy.1 However, there is widespread interest in avoiding surgery for high-risk lesions, the majority of which will not yield a malignant diagnosis on excision.5 Single- institution studies have identified various patient, pathologic, and radiologic variables associated with risk of upgrade on excision, but insufficient evidence is available to inform evidence-based guidelines as to which patients with high-risk lesions can safely avoid excision.5-7 There is also uncertainty about long-term breast cancer risk and the need for enhanced prevention and detection strategies among women who do not undergo excision, or who undergo excision without upgrade.8-10 Our goal is to provide definitive new evidence to guide clinical management recommendations for high-risk breast lesions. We propose a comprehensive study leveraging the rich infrastructure and longitudinal data of the Breast Cancer Surveillance Consortium, a large U.S. alliance of breast imaging and pathology registries. We will supplement the existing BCSC database with newly collected data from breast imaging reports, pathology reports, and other clinical medical records for over 7,000 high-risk lesions diagnosed at more than 100 healthcare facilities since 2010. Using an ensemble learning approach we will develop and validate prediction models for risk of upgrade on excision (Aim 1) and 5- year breast cancer incidence among women with high-risk lesions (Aim 2) based on patient, pathologic, and radiologic factors. In Aim 3 we will use a decision analysis framework paired with qualitative study of stakeholder perspectives to evaluate the potential population impact and acceptability of risk-based strategies for managing high-risk lesions. Our results will facilitate identification of women with acceptably low risk of upgrade on excision who can be safely managed by imaging surveillance, and identify women with elevated risk of a future cancer diagnosis who need enhanced long-term imaging surveillance and/or chemoprevention. The proposed study will be far larger and more representative of clinical practice in the U.S. than any study conducted to date, and will be the first to comprehensively evaluate patient, biopsy, pathologic, and radiologic factors in relation to high-risk lesion outcomes in a multicenter study. Evidence generated by this study will inform clinical recommendations for the management of high-risk lesions diagnosed with core needle biopsy, resulting in improved care and reduced harms for the >100,000 women diagnosed annually in the U.S.