Structure and expression of c‐erbB‐2 and EGF receptor genes in inflammatory and non‐inflammatory breast cancer: Prognostic significance

Abstract

C-erbB-2 and epidermal growth factor receptor (EGFR) genes were independently shown to be associated with breast cancer progression. In this report, we have analyzed the structure and expression of these 2 genes in the same tumor specimens of a large series of breast cancers. Two clinical types of tumor were studied: inflammatory (IBC) and non-inflammatory breast cancers (NBC) obtained from 221 untreated patients at different clinical stages. Amplification and over-expression of the c-erbB-2 proto-oncogene were observed in 27% and 47% of tumors, respectively, and were strongly associated with breast cancers of the most unfavorable prognosis, namely IBC and NBC with multiple positive axillary nodes. EGFR gene was neither amplified nor rearranged. A restriction fragment length polymorphism (RFLP) for HindIII endonuclease was observed. EGFR transcripts were detected in 46% of tumors and observed more frequently in IBC than in NBC (p less than 0.02). In NBC the presence of EGFR transcripts increased linearly with lymph-node involvement and was associated with estrogen-receptor-negative tumors (p = 0.01). Analysis of both genes from the same tumor samples indicated that genes are associated with cancer aggressiveness. Furthermore, in NBC these 2 genes were independently activated, in contrast to IBC in which activated genes were negatively correlated, suggesting that c-erbB-2 and EGFR genes play different roles in NBC and IBC.

Differences in survival among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early

“…26 As such, there are currently several prospective studies evaluating inhibitors of angiogenesis (eg, bevacizumab) for the treatment of IBC. 27 A higher frequency of overexpression of human epidermal growth factor receptor 2 (HER2) among IBC tumors compared with non-IBC tumors has also been reported, 28,29 making HER2-directed targeted therapy with adjuvant trastuzumab important. Women In conclusion, in this large population-based study, we demonstrated that in the era of the use of anthracyclines and taxanes, survival differences between women with stage IIIB/C IBC and those with non-IBC LABC are still present, with differences observed early.…”

c-erbB-2 oncogene as a prognostic marker in breast cancer

“…The results of these studies have varied considerably but several studies have found consistent results with respect to certain prognostic factors. The original study reported by Slamon et al (1987) showed a positive association between c-erbB-2 expression and the number of involved axillary nodes, this finding has not been generally reproducible but finds some support in three other studies (Tandon et al, 1989;Guerin et al, 1989;May et al, 1990) and indirectly in the study by Zhou et al (1989) ship between c-erbB-2 expression and other markers of differentiation. Ploidy has previously been investigated by two groups neither of whom found any significant association (Tavassoli et al, 1989;Ro et al, 1989) At least 20 other groups have now published data concerning the prognostic significance of c-erbB-2, of these only four groups have failed to find a prognostic effect of c-erbB-2 in at least one sub group (Zhou et al, 1989;Ali et al, 1988;Gusterson et al, 1988;Barnes et al, 1988).…”

Gene dosage PCR and fluorescence in situ hybridization reveal low frequency of egfr amplifications despite protein overexpression in invasive breast carcinoma

“…The overexpression of the receptor protein confers a transformed phenotype to NIH 3T3 cells 1 and could be demonstrated in various human malignancies. Different authors reported egfr amplifications in 0-15% of human breast carcinomas 2,3 and EGFR protein overexpression in 16.4%. 4 Although, numerous studies have shown its prognostic significance, [4][5][6][7] the most recent literature characterized EGFR as a factor of doubtful prognostic significance in human breast cancer.…”