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Assessing neoadjuvant treatment response through serum human epidermal growth factor receptor 2 (HER2) dynamics
Xuliren Wang1,2, Min Xiong1,2, Zhibo Shao1,2
1Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
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.
Insights
Early reduction in serum HER2 (sHER2) levels after neoadjuvant therapy (NAT) predicts pathological complete response (pCR) in HER2-positive breast cancer (BC). Monitoring sHER2 dynamics offers a non-invasive approach to guide treatment decisions.
Area of Science:
- Oncology
- Biomarkers
- Breast Cancer Research
Background:
- HER2-positive breast cancer (BC) requires neoadjuvant therapy (NAT), but treatment responses vary.
- Current biomarkers for predicting outcomes are limited.
- Serum HER2 (sHER2) is a promising non-invasive biomarker, but its dynamic changes during treatment need further investigation.
Purpose of the Study:
- To investigate the potential of sHER2 dynamics as a predictor of pathological complete response (pCR) in HER2-positive BC patients undergoing NAT.
- To assess the association between changes in sHER2 levels and pCR achievement.
Main Methods:
- Retrospective analysis of 120 HER2-positive BC patients treated with NAT.
- sHER2 levels measured at baseline, after the second cycle (C2), and at surgery.
- Logistic regression used to analyze the association between sHER2 changes and pCR, considering clinicopathological factors.
Main Results:
- sHER2 levels significantly declined during NAT, with a more pronounced reduction in patients achieving pCR.
- A significant reduction in sHER2 levels after C2 was strongly associated with pCR.
- Early sHER2 changes (baseline to C2) showed a stronger predictive value for pCR than later changes.
Conclusions:
- Reductions in sHER2 levels after C2 are a strong indicator of favorable treatment response in HER2-positive BC patients.
- Monitoring sHER2 dynamics early in NAT can serve as a useful, non-invasive biomarker to predict pCR.
- sHER2 monitoring may guide therapeutic decisions in clinical practice.
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