Abstract ES9-1: Optimizing treatment of early stage triple negative breast cancer: Clinical challenges and new scientific horizons

Abstract

“Triple negative” breast cancer (TNBC) as defined by the lack of estrogen and progesterone receptors and absence of Her2-overexpression, is challenging due to its aggressive natural history and limited treatment options. However, significant progress has been made in the last decade in understanding the biological diversity of TNBC, its prognosis and approaches to successful treatment. For example, molecular classification by gene expression studies initially identified a basal molecular subtype enriched for TNBC, which was further refined to additional include 4 major subtypes: basal-like, mesenchymal, luminal androgen receptor and immune-enriched. In addition, clear associations between TNBC and mutations in DNA-repair-related genes, especially BRCA-1 and BRCA-2 have been elucidated. These findings have subsequently guided therapeutic development. The early-stage setting has been the focus of much of this work, as it is clear that patients who have tumors that respond vigorously to chemotherapy preoperatively have a reduced likelihood of later metastatic recurrence compared to those who have poorly-responsive disease. Capitalizing on this knowledge, trials in the neoadjuvant setting have defined the importance of pathologic complete response (pCR) as a surrogate endpoint, and have shed light on differential effects of standard therapy (such as platinums), development of new targeted therapies (such as PARP inhibitors) and the role of immunotherapy. The high rate of observed recurrence in patients who have high stage disease at diagnosis, or, in particular, residual disease after neoadjuvant therapy, has also led to the launch of clinical trials in the adjuvant and post-neoadjvuant setting designed to specifically address micrometastatic minimal residual disease and therapy resistance. The advantage of the post-neoadjvuant approach to trials amongst patients with residual disease is to decrease the size of adjuvant trials, and allow them to be focused within populations most at risk of recurrence, sparing those with good prognosis the need for additional, potentially toxic treatment. Despite this progress, there are still many unanswered questions regarding optimal therapy and potential to improve outcomes in TNBC. This session will review the state of the science with regard to biology, new treatment approaches, and the value of both the neoadjuvant and post-neoadjvuant settings in developing optimal approaches to tailor therapy on the basis of risk stratification, reduce recurrence, and improve outcomes for women presenting with triple negative breast cancer. Citation Format: DeMichele A. Optimizing treatment of early stage triple negative breast cancer: Clinical challenges and new scientific horizons [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES9-1.