Neoadjuvant Chemotherapy Induces Expression Levels of Breast Cancer Resistance Protein That Predict Disease-Free Survival in Breast Cancer

• DOI: 10.1371/journal.pone.0062766
• Publication Date: 2013-05-03T04:15:01Z
• Authors: Baek Kim; Hiba Fatayer; Andrew M. Hanby; Kieran Horgan; Sarah L. Perry; Elizabeth M.A. Va...; Eldo T. Verghese; Bethany J. Williams; James L. Thorne; Thomas A. Hughes
• Keywords: Abcg2; P-glycoprotein

Three main xenobiotic efflux pumps have been implicated in modulating breast cancer chemotherapy responses. These are P-glycoprotein (Pgp), Multidrug Resistance-associated Protein 1 (MRP1), and Breast Cancer Resistance (BCRP). We investigated expression of these proteins cancers before after neoadjuvant (NAC) to determine whether their levels define response NAC or subsequent survival. Formalin-fixed paraffin-embedded tissues were collected representing matched pairs core biopsy (pre-NAC) surgical specimen (post-NAC) from 45 patients with invasive ductal carcinomas. regimes anthracyclines +/− taxanes. Immunohistochemistry was performed for Pgp, MRP1 BCRP quantified objectively using computer-aided scoring. Pgp significantly up-regulated exposure (Wilcoxon signed-rank p = 0.0024 p<0.0001), while showed more variation NAC, frequent up- (59% cases) down-regulation (41%) contributing a lack significant difference overall. Pre-NAC all markers, post-NAC did not correlate disease-free survival (DFS). Post-NAC response, but correlated DFS (Log rank 0.007), longer low expression. In multivariate Cox regression analyses, proved predict independently standard prognostic factors, high associated hazard ratio 4.04 (95% confidence interval 1.3–12.2; 0.013). conclude that NAC-induced cancer, little predictive value.