A prospective single-center cohort study: integrating PET imaging and genomics to identify early biomarkers of response to dual-targeted PH neoadjuvant therapy in breast cancer.

[BACKGROUND] We aimed to investigate potential biomarkers for predicting pathological complete response (pCR) to neoadjuvant therapy in HER2-positive breast cancer, with a focus on early-stage indicators.

[METHODS] We conducted a comprehensive analysis incorporating genomic and PET imaging data from 61 patients undergoing neoadjuvant treatment. Genomic profiling and PET/CT scans were performed at baseline (T1) and after one treatment cycle (T2). Various clinical and molecular parameters were assessed, including HER2 gene status, maximum standardized uptake value, and genomic alterations.

[RESULTS] Our findings revealed several candidate biomarkers associated with treatment response. Early changes in 18 F-FDG PET/CT and baseline 68 Ga-HER2 PET/CT emerged as potential predictors for pCR. Genomic analysis identified differences in mutation frequencies, with notable changes after one treatment cycle. A multivariate predictive model, incorporating PET imaging and clinical characteristics, demonstrated excellent performance in forecasting treatment response.

[CONCLUSIONS] The study underscores the significance of early biomarkers in predicting neoadjuvant treatment outcomes for HER2-positive breast cancer. Integrating genomic and imaging data provides a comprehensive approach for tailoring therapeutic strategies. The identified biomarkers hold promise for guiding treatment escalation or de-escalation, presenting a step forward in personalized management for HER2-positive breast cancer patients.