Role of immunotherapy in early breast cancer: past, present, and future

The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment over the last decade, starting with the US Food and Drug Administration (FDA) approval of ipilimumab in 2011. Since that time, the FDA has approved nine additional ICIs, which now serve as frontline agents in lung, colorectal, head and neck, genitourinary, and skin cancers. ICIs have been practice-changing across many cancer subtypes, and their role in breast cancer (particularly in early-stage disease) is a topic of ongoing research. The only current FDA-approved ICI indication in early breast cancer is for the use of pembrolizumab in high-risk, triple-negative breast cancer in combination with chemotherapy, based on results from the KEYNOTE-522 trial. Although numerous trials have further investigated the use of ICIs in early-stage triple-negative breast cancer, survival outcomes have been inconsistent. Studies investigating the use of ICIs in early-stage estrogen receptor-positive and human epidermal growth factor receptor 2-positive breast cancer are even more limited, although available data (especially for estrogen receptor-positive disease) are promising. Numerous studies are ongoing, including critical investigations into biomarkers that may help determine which patients with breast cancer are most likely to benefit from the addition of immunotherapy. In this review, we discuss the history of ICI development, key trials investigating the use of ICIs in early-stage breast cancer, and future directions in the field.