Neoadjuvant approach as a platform for treatment personalization: focus on HER2-positive and triple-negative breast cancer

The neoadjuvant setting provides unquestionable clinical benefits for high-risk breast cancer (BC) patients, mainly in terms of expansion of locoregional treatment options and prognostic stratification. Additionally, it is also emerging as a strategical tool in the research field. In the present review, by focusing on HER2-positive and triple-negative subtypes, we examined the role of the neoadjuvant setting as a research platform to facilitate and rationalize the placement of escalation strategies, promote the adoption of biomarker-driven approaches for the investigation of de-escalated treatments, and foster the conduction of comprehensive translational analyses, thus ultimately aiming at pursuing treatment personalization. The solid prognostic role of pathologic complete response after neoadjuvant therapy, and its use as a surrogate endpoint to accelerate the drug approval process were discussed. In this context, available data on escalated treatment strategies capable of enhancing pathologic complete response (pCR) rate or improving prognosis of patients with residual disease (RD) after neoadjuvant treatment, were comprehensively reviewed. We also summarized evidence regarding the possibility of obtaining pCR with de-escalated strategies, with particular emphasis on the role of biomarker-driven approaches for patient selection. Pitfalls of the dichotomy of pCR/RD were also deepened, and data on alternative/complementary biomarkers with a possible clinical relevance in this regard were reviewed.