1. ¹Department of Medical Oncology, National Cancer Research Institute, Genoa, Italy
2. ²Trials Unit, National Cancer Research Institute, Genoa, Italy
3. ³Pathology Unit, National Cancer Research Institute, Genoa, Italy
4. ⁴Ospedale C Poma, Mantova, Italy
5. ⁵UO Oncologia Medica, ASL 1, Sassari, Italy
6. ⁶Ospedale Galliera, Genoa, Italy
7. ⁷Ospedale Civile, Sestri Levante (Ge), Italy
8. ⁸Oncologia Medica, ASL 19, Asti, Italy
9. ⁹Oncologia Medica, Ospedale Casale Monferrato, Italy

Correspondence: Dr L Del Mastro, Department of Medical Oncology, National Cancer Research Institute, L. go Rosanna Benzi 10, 16132 Genova, Italy. E-mail: lucia.delmastro@istge.it

¹⁰See Appendix A1

Received 14 January 2005; Revised 11 May 2005; Accepted 11 May 2005; Published online 21 June 2005.

Abstract

No data are available on the role of HER2 overexpression in predicting the efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients. We retrospectively evaluated this role in patients enrolled in a phase III study comparing standard FEC21 (5-fluorouracil, epirubicin, and cyclophosphamide, administered every 3 weeks) vs dose-dense FEC14 (the same regimen repeated every 2 weeks). HER2 status was determined for 731 of 1214 patients. Statistical analyses were performed to test for interaction between treatment and HER2 status with respect to event-free survival (EFS) and overall survival (OS); EFS and OS were compared within each HER2 subgroup and within each treatment arm. Median follow-up was 6.7 years. Among FEC21-treated patients, both EFS (HR=2.07; 95% CI 1.27–3.38) and OS (HR=2.47; 95% CI 1.34–4.57) were significantly worse in HER2 + patients than in HER2 - patients. Among FEC14-treated patients, differences in either EFS (HR=1.21; 95% CI 0.65–2.24) or OS (HR=1.85; 95% CI 0.88–3.89) between HER2 + and HER2 - patients were not statistically significant. Interaction analysis suggested that the use of dose-dense FEC14 might remove the negative prognostic effect of HER2 overexpression on EFS and OS. Our data suggest a potential role of HER-2 overexpression in predicting the efficacy of dose-dense epirubicin-containing chemotherapy and the need to confirm this hypothesis in future prospective studies.