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

Covid-19大流行期间的乳腺癌新辅助内分泌治疗：新治疗模式的机会？

• 批准号: 10425018
• 负责人: Sarah Jane Nyante
• 金额: $ 18.17万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-10 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10425018
• 关键词: Address; Affect; Aftercare; Area; Aromatase Inhibitors; Biopsy; Body mass index; Breast Cancer Patient; Breast Cancer Treatment; COVID-19 pandemic; Cancer Burden; Cancer Prognosis; Caring; Cell Proliferation; Cessation of life; Characteristics; Clinical/Radiologic; Data; Development; Diagnosis; Disease; Disease Progression; Endocrine; Equipment; Estrogen Receptors; Ethnic Origin; General Population; Health Insurance; Health system; Individual; Insurance Coverage; Knowledge; Malignant Neoplasms; Medical; Meta-Analysis; Mission; Morbidity - disease rate; Neoadjuvant Therapy; Newly Diagnosed; Nodal; North Carolina; Operative Surgical Procedures; Outcome; Patients; Performance; Persons; Pharmaceutical Preparations; Population; Postmenopause; Predictive Factor; Prognosis; Prognostic Factor; Public Health; Race; Radiology Specialty; Recurrence; Research; Retrospective cohort; Risk; Stage at Diagnosis; Subgroup; Support System; Tamoxifen; Time; Tumor stage; Universities; Woman; alternative treatment; cancer surgery; cancer survival; chemotherapy; deprivation; design; experience; hormone receptor-positive; hormone therapy; improved; indexing; infection management; infection risk; low and middle-income countries; malignant breast neoplasm; mortality; mortality risk; pandemic disease; patient population; patient prognosis; patient subsets; preservation; prevent; prognostic; prognostic index; receptor expression; response; rural residence; socioeconomics; standard care; treatment as usual; treatment strategy; tumor

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.

新辅助内分泌治疗(NET；手术前使用抗内分泌药物治疗)已被提出。 作为一种有希望的支持系统来解决乳腺癌患者的手术延误，但更好的 需要在广泛的患者中了解NET的影响，然后才能 融入到日常护理中。手术是乳腺癌的标准治疗方法，但高达36%的乳腺癌患者 美国在建议的时间内不接受手术。将手术推迟&gt；6周 与乳腺癌死亡率相对增加82%相关，从而弥合了这一保健差距 替代疗法，如Net，可能大大提高这一亚群患者的存活率。 NET的临床和放射学响应率与更常用的 新辅助化疗对激素受体阳性患者有很强的治疗潜力 (HR+)乳腺癌，特别是那些预计不会从化疗中获得任何好处的人。网络 在新冠肺炎大流行之前很罕见(约占II-III期HR+的3%)，通常为患者保留 手术前需要细胞减少术。因此，大多数先前评估两者之间关系的研究 净值和治疗终点，如细胞增殖(即Ki-67表达)、肿瘤大小、雌激素受体、 和结节状态，过多地代表大肿瘤患者和诊断的后期。几乎没有几个 过去研究中观察到的预后因素的净相关变化是否可以 推广到更广泛的HR+乳腺癌患者，包括那些患有 较小的早期肿瘤，是HR+疾病的特征。因此，这项研究的目的是 是在155名HR+乳房患者的非临床试验人群中评估Net对预后的影响 在新冠肺炎大流行期间在北卡罗来纳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，患者将经历积极的 对净治疗的反应，但反应的大小将因人口和性别而异 社会经济特征。使用内部设计(前/后净额比较)，我们将(目标1) 量化Net对Ki-67、放射肿瘤大小、雌激素受体表达[%]、结节状态和 术前综合预后指数(PEPI)；和(目标2)确定个体水平和结构性因素 与净反应(即目标1所述的预测因素的变化)有关的因素。及时 获得外科护理并不总是可行的。制定替代治疗策略，以缓解 手术延迟的影响可能会降低乳腺癌发病率增加的风险，而长期的解决方案 都是开发出来的。这项拟议的研究将通过展示网络在现实世界中的影响来帮助填补这一空白 HR+乳腺癌患者的一般人群。