ERBB2 oncogene in human breast cancer and its clinical significance

Cofactor competition between the ligand-bound oestrogen receptor and an intron 1 enhancer leads to oestrogen repression of ERBB2 expression in breast cancer

“…In situ hybridization studies and targeted gene disruption in mice have shown that this protein plays a key role in neural and cardiac development (Lee et al, 1995;Marchionni et al, 1995). The protein is only expressed at low levels in most normal adult tissues, but is overexpressed in a number of human tumours, including 25 ± 30% of breast carcinomas, where it is a marker of poor prognosis (Slamon et al, 1987;Revillion et al, 1998). In addition, experiments in vitro and in transgenic mice have shown that overexpression of ERBB2, or its rodent counterpart, c-neu, in breast epithelial cells can result in cellular transformation (DiFiore, 1987;Bouchard et al, 1989;D'Souza et al, 1993).…”

“…This e ect is reversed in the presence of anti-oestrogens such as tamoxifen and ICI 182780; an observation that clearly has signi®cant implications for anti-oestrogenic therapy for breast cancer, particularly in the area of tamoxifen resistance. Work in cell lines has demonstrated that overexpression of ErbB2 in ER positive cells can result in resistance to tamoxifen (Pietras et al, 1995) and studies in patients have also linked ERBB2 overexpression with a poor response to anti-oestrogen therapy (Newby et al, 1997;Revillion et al, 1998). It is therefore important to understand the molecular mechanism behind the cross talk between these signalling pathways.…”

Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation

“…Overexpression of ErbB2 is associated with poor prognosis, especially in patients with lymph node involvement (Hynes and Stern, 1994;Revillion et al, 1998;Slamon et al, 1987). In phase III clinical trials of a recombinant humanized anti-ErbB2 monoclonal antibody, targeting of breast cancer cells overexpressing ErbB2 results in growth inhibition and regression of tumors (reviewed in: Nass et al, 1998).…”

Strong Correlation between Results of Fluorescent In Situ Hybridization and Immunohistochemistry for the Assessment of the ERBB2 (HER-2/neu) Gene Status in Breast Carcinoma

“…The range of positivity found in the various studies seems to be rather large: 5 to 55% for the amplification, and 10 to 55% for the overexpression (6). Indeed, results of molecular methods may be affected by the dilution of tumor material by normal cells and by the determination of the threshold defining the existence of an amplification or an overexpression (2,7,21).…”

“…Several works suggest that this amplification/overexpression is associated with poor prognosis in breast carcinoma, especially in node positive cases (1-5; for review, see 6,7) and that it could be a marker of reduced response to chemotherapy (3,4,8,9; for review, 6, 7). Conversely, whereas some authors provided data suggesting that ERBB2 expression was a marker of preferential response to anthracycline-containing regimens (10 -11), others found no significant correlation (12)(13)(14).…”