Identification of high-risk breast cancer patients from genetic changes of their tumors.
To identify the genetic prognostic markers for breast cancer, we analyzed loss of heterozygosity (LOH) at 11p, 16q, 17p, 17q, and 18q, as well as amplification of the ERBB2, INT2, and MYC genes, in 131 patients with breast carcinoma, 49 of whom had lymph node involvement, but none of whom had distant metastases. Among the several chromosome arms tested, LOH at 17q was correlated with lymph node metastasis. Amplification of the ERBB2, MYC, and INT2 genes was found more frequently in tumors from patients with lymph node metastases than in tumors from those without lymph node metastases. Univariate analysis demonstrated that LOH at 17q and INT2 amplification were factors influencing disease-free survival (DFS). A multivariate analysis was performed on 89 tumors that were able to be evaluated for both LOH at 17q and INT2 amplification, and the results showed that patients who had tumors with these genetic changes were more likely to have a poor prognosis. The findings of this study suggest that investigating genetic changes, in addition to conventional clinicopathologic factors, may contribute to defining groups of breast cancer patients with differences in prognosis.
Watatani
M
M
First Department of Surgery, Kinki University School of Medicine, Osakasayama, Japan.
Inui
H
H
Nagayama
K
K
Imanishi
Y
Y
Nishimura
K
K
Hashimoto
Y
Y
Yamauchi
E
E
Hojo
T
T
Kotsuma
Y
Y
Yamato
M
M
Matsunami
N
N
Yasutomi
M
M
D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008593:Menopause; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models
D004273:DNA, Neoplasm