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

SIMPLE SUMMARY: Neoadjuvant treatment with anti-HER2 drugs such as trastuzumab or pertuzumab improves outcomes in patients with HER2-positive breast cancer. However, resistance to this treatment in some patients determines a need to identify genetic biomarkers able to predict patient responses and optimize personalized treatments. In this work, two different SNPs (rs1058808 HER2Ala1170Pro and rs2070096 BARD1Thr351=) are proposed as potential biomarkers of a good response to anti-HER2 treatment in patients with early HER2-positive breast cancer. ABSTRACT: 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.