Breast cancer neoadjuvant endocrine therapy during the Covid-19 pandemic: Opportunity for a new treatment paradigm?

新辅助内分泌治疗（NET;术前使用抗内分泌药物治疗）已被建议 作为一个有前途的支持系统，解决乳腺癌患者手术延迟，但更好的 了解NET在广泛的患者中的影响， 纳入常规护理。手术是乳腺癌的标准治疗方法，但在美国， 美国在建议的时间内不接受手术。手术延迟超过6周， 与乳腺癌死亡率相对增加82%相关，从而弥补了护理方面的差距， 诸如NET的替代治疗可以显著改善这一亚组患者的存活率。 NET产生的临床和放射学反应率与更常用的 新辅助化疗，并有很大的潜力，作为治疗激素受体阳性患者 (HR+）乳腺癌，特别是那些预计不会从化疗中获益的人。净 在COVID-19大流行之前很罕见（约3%的II-III期HR+），通常仅用于患者 需要在手术前进行细胞减灭因此，大多数先前的研究评估了 NET和治疗终点，如细胞增殖（即，Ki-67表达）、肿瘤大小、雌激素受体、 和淋巴结状态，大肿瘤患者占多数，诊断时分期较晚。很少 数据，以解决在过去的研究中观察到的NET相关的预后因素的变化是否可以 将其推广至更广泛的HR+乳腺癌患者人群，包括 较小和早期肿瘤是HR+疾病的特征。因此，本研究的目的 在155例HR+乳腺癌患者的非临床试验人群中评价NET的预后影响 在新冠肺炎大流行期间在北卡罗来纳州大学卫生系统接受治疗的癌症患者， 包括那些患有早期疾病的人。我们的基本假设是，患者会经历一个积极的 对NET治疗的反应，但反应的程度将因人口统计学和 社会经济特征使用人内设计（NET前后比较），我们将（目标1） 量化NET对Ki-67、放射学肿瘤大小、雌激素受体表达[%]、淋巴结状态的影响， 复合术前预后指数（PEPI）;（目的2）识别个体水平和结构因素 与NET响应相关联的（即，目标1中描述的预后因素的变化）。及时 接受外科治疗并不总是可行的。制定替代治疗策略， 手术延迟的影响可能会降低更高的乳腺癌发病率的风险， 是发达的。拟议的研究将有助于填补这一空白，通过展示NET在现实世界中的影响， HR+乳腺癌患者的一般人群。

Neoadjuvant endocrine therapy (NET; pre-surgical treatment with an anti-endocrine drug) has been suggested as a promising support system for addressing surgical delays among breast cancer patients, but a better understanding of the impact of NET among a broad cross-section of patients is needed before it can be integrated into usual care. Surgery is a standard treatment for breast cancer, but up to 36% of patients in the US do not receive surgery within the recommended time period. Delaying surgery by >6 weeks has been associated with an 82% relative increase in breast cancer death, thus bridging this gap in care with alternative treatments such as NET may substantially improve survival among this subset of patients. NET produces similar rates of clinical and radiologic response when compared with the more commonly used neoadjuvant chemotherapy and has strong potential as a treatment for patients with hormone receptor-positive (HR+) breast cancer, particularly those who are not expected to derive any benefit from chemotherapy. NET was rare (~3% of stage II-III HR+) before the COVID-19 pandemic, and was generally reserved for patients needing cytoreduction prior to surgery. As such, most prior studies evaluating the relationship between the NET and treatment endpoints, such cellular proliferation (i.e., Ki-67 expression), tumor size, estrogen receptor, and nodal status, over-represented patients with large tumors and a later stage at diagnosis. There are few data to address whether NET-associated changes to prognostic factors observed in past studies can be generalized to the broader population of patients with HR+ breast cancer, including those with the smaller and earlier stage tumors that are characteristic of HR+ disease. Therefore, the objective of this study is to evaluate the prognostic impact of NET in a non-clinical trial population of 155 patients with HR+ breast cancer who were treated in the University of North Carolina Health system during the Covid-19 pandemic, including those with early stage disease. Our underlying hypothesis is that patients will experience a positive response to NET treatment, but that the magnitude of the response will vary by demographic and socioeconomic characteristics. Using a within-person design (pre-/post-NET comparison), we will (Aim 1) quantify the effect of NET on Ki-67, radiologic tumor size, estrogen receptor expression [%], nodal status, and the composite pre-operative prognostic index (PEPI); and (Aim 2) identify individual-level and structural factors that are associated with NET response (i.e., change in the prognostic factors described in Aim 1). Timely access to surgical care is not always feasible. The development of alternative treatment strategies that mitigate the effects of surgical delays may reduce the risks of greater breast cancer morbidity while long-term solutions are developed. The proposed study will help fill this gap by demonstrating the real-world effects of NET in a general population of patients with HR+ breast cancer.