[Study on the relationship between ultrasound-based response evaluation and pathological outcomes in neoadjuvant...

Objective: To investigate the association between ultrasound response assessment during neoadjuvant therapy and pathological outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Methods: This retrospective study included 609 patients with HER2-positive breast cancer who received neoadjuvant therapy at the Breast Center of Peking University Cancer Hospital between June 1, 2018, and December 31, 2024. Ultrasound response was assessed at cycles 2, 4, 6, and 8 according to the World Health Organization (WHO) response criteria and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and categorized as clinical complete response (cCR), clinical partial response (cPR), clinical stable disease (cSD), or clinical progressive disease (cPD). Patients with cCR or cPR were classified into the response group, whereas those with cSD or cPD were classified into the poor-response group. Pathological complete response (pCR) and Miller-Payne (MP) grade were determined from surgical pathology. The χ² test was used to analyze the associations of ultrasound response with pCR and MP grade. Receiver operating characteristic (ROC) curves and areas under the curves (AUC) were used to assess the performance of ultrasound response in predicting pCR. Results: The overall pCR rate was 67.5% (411/609), with rates of 68.7% (338/492) among patients receiving sequential anti-HER2 neoadjuvant therapy and 62.4% (73/117) among those receiving upfront anti-HER2 neoadjuvant therapy. Except for the WHO assessment at cycle 2, pCR rates differed significantly between the response and poor-response groups at all assessment time points according to both criteria (all P<0.05). The proportions of patients with MP grades 4-5 also differed significantly between the two groups at all assessment time points (all P<0.05). When ultrasound response according to each criterion was combined with clinicopathological factors, all AUC were<0.8, indicating poor predictive performance for pCR. In the upfront anti-HER2 therapy group, pCR rates differed significantly between the response and poor-response groups at cycles 2-6 (all P<0.05); in the sequential anti-HER2 therapy group, significant differences were observed at cycles 4-8 (all P<0.05). The pCR rate did not differ significantly between patients with SD accompanied by tumor enlargement and those with SD accompanied by tumor shrinkage (all P>0.05). Conclusions: During neoadjuvant therapy for HER2-positive breast cancer, a treatment response identified by ultrasound at cycle 2 in patients receiving upfront anti-HER2 therapy or at cycle 4 in those receiving sequential anti-HER2 therapy may be associated with pCR; however, ultrasound assessment has limited predictive value for pCR.