Radiation effects on development of HER2-positive breast carcinomas.
Clin Cancer Res
; 13(1): 46-51, 2007 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-17200337
ABSTRACT
PURPOSE:
Neither hormone-related nor genetics risk factors have been associated with the development of highly proliferative HER2-positive breast carcinomas. Because the majority of HER2-positive tumors present the amplification of the oncogene, we asked whether genomic instability triggered by irradiation might be involved in the induction of HER2-overexpressing breast carcinomas. EXPERIMENTALDESIGN:
Sixty-six infiltrating breast carcinomas from patients treated with radiation therapy for Hodgkin's lymphoma or other pediatric solid tumors and a control series of 61 consecutive sporadic breast tumors were analyzed by immunohistochemistry for HER2 expression with HercepTest. A panel of antibodies against estrogen receptor, progesterone receptor, c-kit, cytokeratin 5/6, p53, and ki67 antigen was also used to identify differentiation subsets and molecular characteristics of the analyzed breast carcinomas.RESULTS:
Although no differences between the two tumor series were found with respect to HER2 expression scored 2+ and 3+, the percentage of 3+ HER2-positive tumors was significantly higher in patients irradiated during breast maturation compared with patients irradiated after breast maturation (35.3% versus 12.5%, P = 0.046). In the latter group, 52.5% of the breast carcinomas showed basal-like differentiation (estrogen receptor, progesterone receptor, and HER2 negative) versus only 5.9% in the group irradiated during breast development (P < 0.0001). Analysis adjusted for age confirmed the significant increase in basal-like tumor development in patients irradiated within 4 years of menarche, but also showed that the differences between patients irradiated before and after puberty in HER2 3+ tumor frequencies are due to age-related differences in HER2 3+ tumor onset.CONCLUSION:
Together, our data indicate that the development of HER2-positive tumors correlates with timing rather than type of carcinogenic hits and provide clear evidence that radiation is a risk factor for breast carcinomas showing basal-like differentiation.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mama
/
Neoplasias da Mama
/
Doença de Hodgkin
/
Regulação Neoplásica da Expressão Gênica
/
Receptor ErbB-2
/
Neoplasias
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Child
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Itália