Studies have emphasized the significance of genotyping GSTP1 and detecting deletions of GSTM1 and GSTT1 genes in predicting the response of breast cancer patients to anthracycline and taxane-based treatment regimens. Nevertheless, there are discrepancies in the data due to the substantial influence of interethnic differences on the prediction of chemotherapeutic response. This study examined the impact of GSTM1 and GSTT1 gene deletions, as well as GSTP1 polymorphism, on the response and toxicity of South Indian patients with locally advanced breast cancer who were undergoing anthracycline-based neoadjuvant chemotherapy. We conducted a prospective study from January 2015 to December 2018. We enrolled 170 patients who had been diagnosed with locally advanced breast cancer and were undergoing treatment with anthracycline-based therapy. The frequencies of the homozygous wild-type variant AA, the heterozygous variant AG, and the mutant homozygous variant GG were 44%, 41%, and 15%, respectively. Out of the 152 patients, 48 successfully attained a pathologic response. Patients with the GSTM1 null variant had a complete pathologic response, whereas those with the GSTM1 gene did not. Additionally, we have noticed a pattern in the susceptibility to neutropenia among patients who had null variants of GSTM1. In our study, South Indian breast cancer patients with the GSTM1 deletion experienced better complete pathological responses.