erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer.
J Natl Cancer Inst
; 90(18): 1361-70, 1998 Sep 16.
Article
em En
| MEDLINE
| ID: mdl-9747867
ABSTRACT
BACKGROUND:
Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis.METHODS:
In National Surgical Adjuvant Breast and Bowel Project protocol B-11, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil (PF) or a combination of L-phenylalanine mustard, 5-fluorouracil, and doxorubicin (PAF). Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS). Reported P values are two-sided.RESULTS:
Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P=.02), lack of estrogen receptors (P=.008), and the number of positive lymph nodes (P=.0001). After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors--DFS relative risk of failure (RR)=0.60 (95% confidence interval [CI]=0.44-0.83), P=.001; survival RR=0.66 (95% CI=0.47-0.92), P =.01; RFS RR=0.58 (95% CI=0.42-0.82), P=.002; DDFS RR=0.61 (95% CI=0.44-0.85), P=.003. However, it was not significant for patients with erbB-2-negative tumors-DFS RR=0.96 (95% CI=0.75-1.23), P=.74; survival RR =0.90 (95% CI=0.69-1.19), P=.47; RFS RR=0.88 (95% CI=0.67-1.16), P=.37; DDFS RR=1.03 (95% CI=0.79-1.35), P=.84. Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P=.02) and DDFS (P=.02) but not for survival (P= .15) or RFS (P=.06).CONCLUSIONS:
These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Doxorrubicina
/
Biomarcadores Tumorais
/
Regulação Neoplásica da Expressão Gênica
/
Receptor ErbB-2
/
Antibióticos Antineoplásicos
/
Neoplasias Hormônio-Dependentes
Tipo de estudo:
Etiology_studies
/
Guideline
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
J Natl Cancer Inst
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos