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The addition to chemotherapy of anti-HER2 drugs such as trastuzumab or pertuzumab has improved outcomes in HER2-positive breast cancer patients. However, resistance to these drugs in some patients remains a major concern. This study examines the possible association between the response to neoadjuvant anti-HER2 treatment in breast cancer patients and the presence of 28 SNPs in 17 genes involved in different cell processes ( PON1 , CAT , GSTP1 , FCGR3 , ATM , PIK3CA , HER3 , BARD1 , LDB2 , BRINP1 , chr6 intergenic region, RAB22A , TRPC6 , LINC01060 , EGFR , ABCB1 , and HER2 ). Tumor samples from 50 women with early breast cancer were genotyped using the iPlex ® Gold chemistry and MassARRAY platform, and patients were classified as good responders (Miller-Payne tumor grades 4-5) and poor responders (Miller-Payne tumor grades 1-3), as assessed upon surgery after 6 months of treatment. Proportions of patients with the HER2Ala1170Pro (rs1058808) SNP double mutation were higher in good (58.62%) than poor (20%) responders ( p = 0.025). Similarly, proportions of patients carrying the synonymous SNP rs2070096 ( BARD1Thr351= ) (wv + vv) were higher in patients showing a pathological complete response (46.67%) than in those not showing this response (15.15%) ( p = 0.031). The SNPs rs1058808 ( HER2Ala1170Pro ) and rs2070096 ( BARD1Thr351= ) were identified here as potential biomarkers of a good response to anti-HER2 treatment.

HER2 and BARD1 Polymorphisms in Early HER2-Positive Breast Cancer Patients: Relationship with Response to Neoadjuvant Anti-HER2 Treatment