Neoadjuvant and adjuvant treatment of patients with HER2-positive early breast cancer.

The availability of HER2-targeted therapy has dramatically improved patient outcome in HER2-positive (HER2+) early breast cancer (EBC) as recently demonstrated by the EBCTCTG metaanalysis on trastuzumab in HER2+ EBC: Adding trastuzumab to chemotherapy has reduced recurrence rates and breast-cancer related mortality by a third [1]. Today, neoadjuvant therapy has become standard of care for women with stage II or III tumors as pathological complete response (pCR) status after surgery can be used to individualize adjuvant systemic therapy. pCR is correlated with favorable patient outcome, particularly in hormone receptor (HR) negative HER2+ EBC, as demonstrated by the FDA meta-analysis. Moreover, for patients with non-pCR, 14 cycles of adjuvant T-DM1 have become a new adjuvant therapy standard based on the results of the KATHERINE trial. Primary surgery can be offered to patients with low tumor burden (cN0 cT1). For this low-risk subgroup, 12 weeks of adjuvant paclitaxel + trastuzumab for one year are correlated with excellent outcome based on the APT trial results. A multidisciplinary team is essential right from the beginning for optimal locoregional and systemic therapy in such a complex neoadjuvant - adjuvant continuum of care. Clinical trials in HER2+ EBC are currently evaluating further therapy de-escalation in low-risk disease or patients with pCR whereas for patients with non-pCR, escalation trials are also ongoing. Newly approved drugs for HER2+ MBC like tucatinib or trastuzumab-deruxtecan or even immunotherapy combinations are being evaluated to improve upon efficacy of T-DM1 alone in the non-pCR setting. Regarding de-escalation, the WSG ADAPT trial demonstrated feasibility of avoiding overtreatment and individualizing neoadjuvant therapy without compromising outcome. Further de-escalation trials (e.g. DECRESCENDO, COMPASS-HER2) are currently ongoing.