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

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.