Optimizing adjuvant and post-neoadjuvant therapy in HER2-positive early breast cancer

Treatment advances have improved outcomes in human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer (eBC) but certain patients remain at high risk of recurrence. Neoadjuvant therapy (NAT) has comparable outcomes to adjuvant therapy with the advantage of surgical down-staging, response assessment, informing prognosis, and tailoring adjuvant treatment. Thus, the standard of care for the majority of HER2-positive eBC has become a combination of chemotherapy and HER2-targeted agents given in the neoadjuvant setting.

Mounting evidence suggests that pathologic complete response after NAT translates to a favorable long-term prognosis. The efficacy and tolerability of post-NAT are key, particularly for patients with residual disease. This is demonstrated, for example, by the use of trastuzumab emtansine in the appropriate clinical setting and various new drugs under investigation. This review summarizes the current clinical management and exciting future directions to optimize outcomes in HER2-positive eBC.

Targeted therapies such as trastuzumab deruxtecan, tucatinib, and immunotherapy have demonstrated impressive responses in metastatic breast cancer, including CNS disease. Incorporating these agents in the post-neoadjuvant space may improve the prognosis of HER2-positive eBC. Future research should prioritize the identification of biomarkers that personalize treatments to achieve maximum benefit and less toxicity.