title: HER2 expression and efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients.
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.
authors.affiliation: Department of Medical Oncology, National Cancer Research Institute, Genoa, Italy. lucia.delmastro@istge.it
authors.forename: L
authors.initials: L
authors.lastname: Del Mastro
authors.forename: P
authors.initials: P
authors.lastname: Bruzzi
authors.forename: G
authors.initials: G
authors.lastname: Nicolò
authors.forename: G
authors.initials: G
authors.lastname: Cavazzini
authors.forename: A
authors.initials: A
authors.lastname: Contu
authors.forename: M
authors.initials: M
authors.lastname: D'Amico
authors.forename: A
authors.initials: A
authors.lastname: Lavarello
authors.forename: F
authors.initials: F
authors.lastname: Testore
authors.forename: B
authors.initials: B
authors.lastname: Castagneto
authors.forename: E
authors.initials: E
authors.lastname: Aitini
authors.forename: L
authors.initials: L
authors.lastname: Perdelli
authors.forename: C
authors.initials: C
authors.lastname: Bighin
authors.forename: R
authors.initials: R
authors.lastname: Rosso
authors.forename: Marco
authors.initials: M
authors.lastname: Venturini
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000627:therapeutic use*; D018734:Genes, erbB-2; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D000903:Antibiotics, Antineoplastic; D015251:Epirubicin