Progress in immune checkpoint inhibition in early-stage triple-negative breast cancer

Immune checkpoint inhibitors have been particularly effective in treating cancers with robust immune microenvironments and have been successfully incorporated into the management of metastatic ER-negative and HER2-negative breast cancer. This has prompted investigation of immunotherapy in early-stage triple negative breast cancer (TNBC) to address the suboptimal clinical outcomes and limited therapeutic options.

This review highlights the studies examining the use of neoadjuvant immunotherapy with standard chemotherapy in the management of early-stage TNBC and explores ongoing areas of study including the role of adjuvant checkpoint inhibition and novel combination therapies with immunotherapy.

The current standard of care for early-stage ER-negative, HER2-negative breast cancer measuring ≥2 cm or with lymph node involvement is neoadjuvant chemotherapy with pembrolizumab followed by ongoing pembrolizumab in the adjuvant setting to complete 1 year of total therapy as per the KEYNOTE-522 study. This approach is associated with improved pathologic complete response (pCR) rate and event free survival, irrespective of PD-L1 status. Many questions remain regarding the optimization of chemotherapy partner(s) for immunotherapy, necessity of adjuvant immunotherapy for patients who achieve pCR, inclusion of other therapies in the adjuvant setting (particularly capecitabine or olaparib), and use of adjuvant immunotherapy when it was not received in the neoadjuvant setting.