Post-Neoadjuvant Treatment in HER2-Positive Breast Cancer: Escalation and De-Escalation Strategies

Simple Summary The response to neoadjuvant treatment is strongly associated with the clinical outcome of breast cancer patients, especially in the HER2-positive subtype of the disease. In HER2-positive patients with a residual tumor burden, an escalation of post-neoadjuvant therapy leads to the improvement of survival, while (post)-neoadjuvant treatment de-escalation is currently being discussed in low-risk settings in order to avoid unnecessary toxicities. Patients with high-risk non-metastatic breast cancer are recommended for chemotherapy, preferably in the neoadjuvant setting. Beyond advantages such as a better operability and an improved assessment of individual prognosis, the preoperative administration of systemic treatment offers the unique possibility of selecting postoperative therapies according to tumor response. In patients with HER2-positive disease, both the escalation of therapy in the case of high-risk features and the de-escalation in patients with a low tumor load are currently discussed. Patients with small node-negative tumors receive primary surgery and, upon confirmation of pathological T1 N0 status, de-escalated adjuvant therapy with paclitaxel and trastuzumab. For those with a large tumor and/or nodal involvement, neoadjuvant polychemotherapy with a dual antibody blockade is recommended. Patients with invasive residual disease benefit from switching postoperative therapy to the antibody-drug-conjugate trastuzumab emtansine (T-DM1). In this review, we discuss current evidence and controversies regarding post-neoadjuvant treatment strategies in HER2-positive breast cancer.