Induction of primary systemic therapy by weekly paclitaxel: Predictive value of hormone receptors, HER-2, topoisomerase II- alpha, and other biological markers in relation to pathological complete response

Abstract

e11525 Background: Randomized phase II study of epirubicin(E) plus cyclophosphamide (C) vs. weekly paclitaxel (P) as primary systemic therapy (PST) in stage II and III breast cancer(BC) have shown that there was no significant difference in the pathological complete response (pCR) rate between the EC and P groups (#568 ASCO 2008). The aim of this study is to evaluate the predictive value of hormone receptors, HER2, topoisomerase IIα(TOP II) and other biological markers in the EC and P groups as PST. Methods: Tissue samples were obtained before PST from pts who were randomized to either Arm A (EC: E 75 mg/m2 and C 600 mg/m2 every 3 W for 4 cycles) or Arm B (weekly P: P 80 mg/m2 weekly for 12 w). Pts received PST for 12 w, then underwent surgery. All pts received a crossover regimen as adjuvant chemotherapy.The pretreatment expression of estrogen receptor (ER), progesterone receptor(PgR), HER2, P53, Ki67, P21 and CD31 were analized by immunohistochemical staining. The status of TOP II gene was evaluated by FISH. Results: One-hundred- sixty pts (Arm A: n=82, Arm B: n=78 ) were estimable. The pCR rates were 13.4% in Arm A and 17.9% in Arm B(p=0.43). In both arms, pCR rate was significantly higher for pts whose tumors did not express ER nor PgR(ER/PgR-) compared with the receptor positive(ER/PgR+) pts. Pts with HER2 positive tumors tend to have higher pCR rate in Arm B compared with Arm A (32.2% vs. 12.5%;p=0.11). The pCR rate for pts with HER2 negative BC were not different in both Arms(A:14.0% vs. B:8.5%). Pts with triple negative (TN) (ER/PgR, HER2-) BC achieved almost same pCR in both Arms (A:25.0% vs. B:23.1%). However, the pCR rate for pts with nonTN BC was significantly higher in ArmB compared to Arm A (16.9% vs. 8.6%, p<0.001). The deletion and amplification of TOP II gene were not predictive of higher pCR rate to ArmA than to Arm B. The pretreatment expression of P53, Ki67, P21 and CD31 was unlikely to predict the higher response of any Arm. Conclusions: Althogh valuable predictive factor of pCR were not detected between EC and weekly P group, the efficacy of weekly P therapy as PST were equal to EC therapy regardless of HR,HER2 and TOP II gene status. Therefore, induction of PST by weekly P therapy seems to be promising. No significant financial relationships to disclose.