Clinical characteristics and survival analysis of HER2 negative breast cancer: AR and negative PD-L1 predict worse pathological complete response rate

Abstract Background: HER2-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared differences between HER2-low and HER2-0 breast cancers, but consensus conclusions have not been reached. Furthermore, a biomarker for predicting pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be discovered. Method: We collected data of 777 patients from three centers (the Cancer Center of Guangdong Provincial People's Hospital, the Oncology Center of the First Affiliated Hospital of Sun Yat-Sen University and the Sun Yat-Sen University Cancer Center), stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could serve as reliable predictors of pCR. Results: The study found higher pCR rates in HER2-0 breast cancers compared to HER2-low tumors (289 patients [30.1%] vs 475 patients [18.1%], p<0.0001). Survival analysis did not show significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts worse pCR rates in both the overall patient cohort and the HER2-0 breast cancer patient cohort (overall patients: OR: 0.479, 95%CI: (0.250, 0.917), p=0.026; HER2-0 patients: OR: 0.267, 95%CI: (0.080, 0.892), p=0.032). In contrast, programmed death ligand 1 (PD-L1) predicts favorable pCR rates in the overall patient cohort (OR: 3.199, 95%CI: (1.020, 10.037), p=0.046). Conclusion: There is insufficient evidence to classify HER2-low breast cancer as a new subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to poorer pCR outcomes.