Phase II, randomized trial of preoperative epirubicin-paclitaxel +/- gefitinib with biomarker evaluation in operable breast cancer

Valentina Guarneri, Antonio Frassoldati, Guido Ficarra, Fabio Puglisi, Claudia Andreetta, Andrea Michelotti, Nicola Cresti, Corrado Boni, Giancarlo Bisagni, Rossana Berardi, Nicola Battelli, Armando Santoro, Giuseppe Banna, Alberto Bottini, Beatrice Di Blasio, Antonino Maiorana, Federico Piacentini, Simona Giovannelli, Gordana Jovic, PierFranco Conte

Research output: Contribution to journalArticle


Purpose: To evaluate the in vivo effect of adding gefitinib to preoperative chemotherapy on the EGFR-dependent p42/44 MAPK in operable breast cancer (BC) patients. Secondary aims: to evaluate EGFR, (p)-EGFR, Ki67, apoptotic index (TUNEL test) and VEGFR2 expression from baseline to surgery, percentage of pathologic complete response (pCR), and toxicity. Patients and Methods: 90 patients with stage II-IIIA BC have been randomized to receive epirubicin 90 mg/sqm and paclitaxel 175 mg/sqm on day 1 plus: gefitinib 250 mg daily from day 5 to 16 (Arm A, intermittent), gefitinib 250 mg daily from day 1 to 21 (Arm B, continuous), or placebo (Arm C). Treatment plan: 4 courses every 3 weeks, followed by surgery. Results: After preoperative therapy, 86/90 patients underwent surgery; 46 patients (51%) received breast conservative surgery. A pCR was observed in 4 patients. No significant differences in the expression of p42/44 MAPK, EGFR, (p)-EGFR, VEGFR2, proliferation index and apoptosis were observed comparing the combined Arms A + B vs C, and comparing Arm A vs B. Hematologic toxicities were not significantly different comparing Arms A + B vs Arm C, and comparing Arm A vs B. Significantly higher skin and mucosal toxicities were observed when comparing the two gefitinib Arms (A + B) vs Arm C (32% vs 9.6%, P = 0.018; 57% vs 29%, P = 0.009 respectively), while no significant differences were observed comparing Arm A vs B. Conclusion: Adding gefitinib to chemotherapy did not result in different effects on the EGFR-dependent pathway, proliferation, apoptosis and VEGFR2 expression as compared to placebo, while enhancing skin and mucosal toxicity. The two schedules of gefitinib (intermittent vs continuous) did not result in different biologic effects.

Original languageEnglish
Pages (from-to)127-134
Number of pages8
JournalBreast Cancer Research and Treatment
Issue number1
Publication statusPublished - Jul 2008



  • Breast cancer
  • Chemotherapy
  • Gefitinib
  • MAPK
  • Primary systemic therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Guarneri, V., Frassoldati, A., Ficarra, G., Puglisi, F., Andreetta, C., Michelotti, A., Cresti, N., Boni, C., Bisagni, G., Berardi, R., Battelli, N., Santoro, A., Banna, G., Bottini, A., Blasio, B. D., Maiorana, A., Piacentini, F., Giovannelli, S., Jovic, G., & Conte, P. (2008). Phase II, randomized trial of preoperative epirubicin-paclitaxel +/- gefitinib with biomarker evaluation in operable breast cancer. Breast Cancer Research and Treatment, 110(1), 127-134.