Assessing neoadjuvant treatment response through serum human epidermal growth factor receptor 2 (HER2) dynamics.

Abstract

Background: Human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancer (BC) accounts for 15-20% of all cases, requiring HER2-targeted neoadjuvant therapy (NAT). Despite the success of trastuzumab and other HER2-targeted treatments, many patients still experience inadequate responses, highlighting the need for more accurate and accessible biomarkers to predict treatment outcomes. Serum HER2 (sHER2) levels, as a non-invasive biomarker, have shown promise in monitoring treatment response; however, the role of sHER2 dynamics during treatment remains underexplored. The aim of this study was to investigate the potential of sHER2 dynamics as a predictor of pathological complete response (pCR) in HER2-positive BC patients undergoing NAT.

Methods: This retrospective study analyzed 120 HER2-positive BC patients who underwent standard NAT followed by surgery at Fudan University Shanghai Cancer Center (FUSCC). sHER2 levels were measured at three time points: baseline, after the second cycle of therapy (C2), and at surgery. Logistic regression analysis was used to assess the association between changes in sHER2 levels and the achievement of pCR. The study also examined the influence of other clinicopathological factors such as estrogen receptor (ER) status, Ki67, and tissue HER2 (tHER2) levels on pCR.

Results: During NAT, sHER2 levels showed a significant decline, with a more pronounced reduction observed in patients achieving pCR. The greatest reduction in sHER2 levels after C2 was strongly associated with pCR. Both univariate and multivariate analyses identified significant reductions in sHER2 levels after C2 and ER-negative status as independent predictors of pCR. Notably, sHER2 changes from baseline to C2 demonstrated a stronger predictive value for pCR compared to changes observed later in treatment.

Conclusions: Our study confirms that reductions in sHER2 levels after C2 are a strong indicator of favorable treatment response in HER2-positive BC patients undergoing NAT. Monitoring sHER2 dynamics early in treatment can serve as a useful, non-invasive biomarker to predict pCR and may guide therapeutic decisions in clinical practice.