Treatment of small (T1mic, T1a, and T1b) node-negative HER2+breast cancer - a review of current evidence for and against the use of anti-HER2 treatment regimens

Introduction Since the advent of anti-HER2 therapies, evidence surrounding adjuvant treatment of small (T1mic, T1a, and T1b), node-negative, HER2-positive breast cancer (HER2+ BC) has remained limited. Practices vary widely between institutions with little known regarding the added benefit of systemic therapy, including cytotoxic chemotherapy and HER2-directed treatments. Our group has set out to perform an extensive review of available literature on this topic. Areas covered In this review, we examined HER2 biology, anti-HER therapies, outcome definitions, and available prospective and retrospective data surrounding the use of adjuvant therapy in those with small, node-negative, HER2+ BC. For outcomes, we primarily explored breast cancer-specific survival (BCSS), invasive disease-free survival (iDFS), and overall survival (OS). We also investigated the incidence of adverse events with a particular focus on symptomatic and asymptomatic declines in ejection fraction. Expert opinion Retrospective data will likely be the main driver for future treatment decisions. Given what we know, high-risk T1b and T1c subgroups derive measurable added benefit from HER2-guided combination therapies but it's not clear whether these benefits outweigh known risks associated with this combination therapy. For tumors <= 0.5 cm (T1mic and T1a), treatment remains highly controversial with limited evidence available through retrospective analysis that suggest over-treatment may be occurring.