Evaluation of the prognostic and predictive value of HER-1/EGFR in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy.
BACKGROUND
To assess the prognostic and predictive significance of HER-1/EGFR protein levels in high-risk patients with breast cancer treated with dose-dense sequential adjuvant chemotherapy.


METHODS
595 high-risk breast cancer patients were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy (E-CMF vs. E-T-CMF). Disease-free survival (DFS) was the primary end point. HER-1/EGFR was assessed by immunohistochemistry (IHC) in 312 patients.


RESULTS
HER-1/EGFR expression was detected in 54 of 312 patients (17%). Positive expression of HER-1/EGFR was significantly associated with negative receptor status (52 vs. 17%, p < 0.001), worse histological grade (70 vs. 45%, p = 0.001), HER-2 overexpression (46 vs. 27%, p = 0.01) and positive p53 expression (48 vs. 19%, p < 0.001). With a median follow-up of 7 years, the total number of relapses was 105 (34%), and the total number of deaths 69 (22%). The analysis for DFS provides significant evidence that the HER-1/EGFR effect on the risk of disease progression was different according to treatment (interaction p = 0.02). Regarding overall survival, a trend towards a significant difference for an interaction of HER-1/EGFR and treatment was found (p = 0.07).


CONCLUSIONS
The present study demonstrated a differential effect of positive HER-1/EGFR expression in the two treatment groups, with HER-1/EGFR being a negative prognostic marker in the absence of paclitaxel.
Tzaida
Olympia
O
Metaxas Cancer Hospital, Piraeus, Greece.
Gogas
Helen
H
Dafni
Urania
U
Kyroudi
Aspasia
A
Papaspyrou
Irene
I
Kyriakou
Vasiliki
V
Malamou-Mitsi
Vasiliki
V
Alamani
Maria
M
Skopa
Chrisoula
C
Kostopoulos
Ioannis
I
Kastritis
Efstathios
E
Pectasides
Dimitrios
D
Briasoulis
Evangelos
E
Kalofonos
Haralabos P
HP
Aravantinos
Gerasimos
G
Fountzilas
George
G
Arapantoni-Dadioti
Petroula
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D011379:Prognosis
D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil; D008727:Methotrexate