P-Glycoprotein Expression in Indian Breast Cancer Patients with Reference to Molecular Subtypes and Response to Anthracycline-Based Chemotherapy-a Prospective Clinical Study from a Developing Country.

Abstract

Chemo-resistance is an important factor determining the response of tumor to neoadjuvant chemotherapy (NACT). Our study was aimed to determine the role of P-glycoprotein (P-glyp) expression as a predictor of response to NACT in locally advanced breast cancer (LABC) patients with special reference to molecular subtypes. Sixty cases of locally advanced breast cancer (LABC) were subjected to trucut biopsy and the tissue samples were evaluated immunohistochemically for P-glyp, ER, PR, and Her 2 neu status. Pre- and post-NACT P-glyp expression was correlated with clinical response (using WHO criteria after three cycles of CEF regimen) and molecular subtypes. The change in the P-glyp expression before (pre-) and after (post-) NACT was statistically significant with higher stage (p = 0.02), hormonal negative molecular subtypes (p = 0.01), and poor clinical response (p = 0.01). Pre-NACT-positive P-glyp expression is associated with higher stage and hormonal negative molecular subtypes and poor clinical response. The increased expression of P-glyp induced by NACT likely explains the concept of acquired chemo-resistance and may prove as an intermediate checkpoint in determining chemo-sensitivity for further treatment so that additional doses of ineffective chemotherapy may be avoided in non-responders translating into better patient safety.