Optimizing HER2-positive breast cancer therapy through neoadjuvant platforms: controversies and concepts

Abstract

HER2-positive breast cancer is a highly aggressive subtype that once had a poor prognosis. While the last two decades have seen progress in multiple HER2-targeting agents that lead to improved patient outcomes, these benefits are accompanied by increased toxicity and great cost. In addition, as not all patients have the same risk of disease, individualized treatment regimens are required. Neoadjuvant therapy can allow surgical de-escalation while also providing efficacy and prognostic information, and for HER2-positive breast cancer, chemotherapy combined with dual HER2-blockade regimens can achieve 42−68% pathologic complete response (pCR) and translate to excellent outcomes. The KATHERINE study showed that adjuvant trastuzumab emtansine (T-DM1) ameliorated invasive disease-free survival (iDFS) significantly in patients with residual disease. However, the question remains as to whether treatment can be tailored for patients with pCR or early response, and several ongoing trials such as CompassHER2 and PHERGain are attempting to address this. Preoperative therapy is currently recommended by the American National Comprehensive Cancer Network (NCCN) and by Chinese Guidelines for HER2-positive breast cancer patients with ≥T2 or ≥N1. For now, we can call neoadjuvant therapy a promising platform for optimizing HER2-positive breast cancer treatment. However, it is an ongoing challenge to individualize management of anti-HER2 regimens, and this narrative review will discuss current trials and comment on several controversial topics based on therapeutic strategies and clinical practices in China.