Immunocytochemical and biochemical analysis of epidermal growth factor receptor expression in human breast cancer tissues: Relationship to estrogen receptor and lymphatic invasion

Toi, Masakazu; Hamada, Yoshiaki; Nakamura, Toshio; Mukaida, Hidenori; Suehiro, Shinichi; Wada, Tsutomu; Toge, Tetsuya; Niimoto, Minoru; Hattori, Takao

doi:10.1002/ijc.2910430208

Cited by 55 publications

(22 citation statements)

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“…High levels of expression of the related epidermal growth factor receptor and c-erbB-2 PTKs in 35 ± 50% and 20 ± 30% of breast tumours respectively have been found to be associated with poor prognosis (Sainsbury et al, 1987;Slamon et al, 1987Slamon et al, , 1989Harris et al, 1989;Grimaux et al, 1989;Toi et al, 1989;Nicholson et al, 1991;Gullick et al, 1991;Paterson et al, 1991;Gusterson et al, 1992). Further, studies in animal model systems have supported the hypothesis that elevated expression of such molecules can predispose to tumour development.…”

Section: Introductionmentioning

confidence: 98%

BRK tyrosine kinase expression in a high proportion of human breast carcinomas

1997

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Section: Introductionmentioning

confidence: 98%

BRK tyrosine kinase expression in a high proportion of human breast carcinomas

1997

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“…As noted above PgR subdivides ER-positive tumours. A more powerful factor for subdividing ERnegative tumours is epidermal growth factor receptor (EGFR) expression, which is inversely related to ER expression (Sainsbury et al, 1985;Toi et al, 1989;McClelland et al, 1993 al., 1980) and it is still measurable in patients' blood 6 weeks after stopping tamoxifen therapy (Fabian et al, 1981). In early studies virtually all the repeat tumour biopsies were taken with the patients on tamoxifen treatment.…”

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confidence: 99%

Oestrogen receptor: a stable phenotype in breast cancer

Robertson

1996

Br J Cancer

127

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Summary Oestrogen receptor (ER) expression in breast cancer is regarded as a phenotype that may change during the natural history of the disease or during endocrine therapy. It has been suggested that in up to 70% of tumours that show acquired resistance the mechanism may be changed in ER status from positive to negative. This paper proposes an alternative hypothesis that ER expression is a stable phenotype in breast cancer. The paper reviews the literature on ER expression during the natural history of breast cancer in patients and also presents data on the effect of endocrine therapy on ER expression. If the alternative hypothesis is true it has important implications for treatment from chemoprevention to acquired endocrine resistance in advanced disease. Equally, if the hypothesis is true, attempts to develop laboratory models of endocrine resistance where ER-positive tumours become ER negative need to be re-evaluated.Keywords: breast cancer; oestrogen receptor; stable phenotypeThe oestrogen receptor (ER) is a 65 kDa oestrogen-binding protein expressed by 46-77% of breast cancers (Walt et al., 1976;Knight et al., 1977; Maynard et al., 1978;Brooks et al., 1980;Osborne et al., 1980; Croton et al., 1981;Howell et al., 1984;Hawkins et al.,1987a;Williams et al., 1987;Clarke and McGuire, 1988). It is a generally held view that ER expression is not a permanent phenotype in breast cancer cells Moolgavakar et al., 1980; Encarnacion et al., 1993; Morrow and Jordon, 1993;Nomura et al., 1985;Jordan, 1994;Paik et al., 1994). One reason for this view is the belief that patients with ER-positive primary breast tumours often develop ER-negative metastases in regional lymph nodes or distant sites. This has been interpreted to show that ER negativity correlates with more aggressive tumour biology and loss of cellular control. A second reason is the strong correlation between ER and therapeutic response to primary endocrine therapy (Samaan et al., 1981;Howell et al., 1984;Williams et al., 1987), which formed the basis for early hypotheses of endocrine sensitivity and resistance. Up to 60% of ER-positive tumours respond to hormone therapy (e.g. Tamoxifen), while for ER-negative tumours the figure is around 10% Samaan et al., 1981;Williams et al., 1987). Therapeutic response to endocrine therapy is not permanent and eventually all such tumours progress. As ER negativity is strongly associated with primary resistance to endocrine therapy it is generally accepted that when responding tumours subsequently progress that in the majority of tumours this is due to loss of ER expression by the tumour Moolgavakar et al., 1980;Nomura et al., 1985; Encarnacion et al., 1993;Morrow and Jordan, 1993;Jordan, 1994;Paik et al., 1994). This paper proposes the alternative hypothesis that ER is a stable phenotype in breast cancer cells.The discovery of monoclonal antibodies (Kohler and Milstein, 1975) subsequently led to specific antibodies being raised to ER (Green and Jensen, 1982 . The ER-ICA allowed assessment of tumour tissue sections (King ...

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“…Many studies in recent years have shown an inverse relationship between ER and EGFR in female human breast cancer (Sainsbury et al, 1985;Toi et al, 1989;Lewis et al, 1990). EGFR expression in human breast cancer is associated with a number of features of poor prognosis, including high tumour grade (Hainsworth et al, 1991), lymphatic invasion (Toi et al, 1989(Toi et al, , 1990, lymph node involvement (Hainsworth et al, 1991) and markers of increased cellular proliferation such as Ki-67 (Toi et al, 1990).…”

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confidence: 99%

“…EGFR expression in human breast cancer is associated with a number of features of poor prognosis, including high tumour grade (Hainsworth et al, 1991), lymphatic invasion (Toi et al, 1989(Toi et al, , 1990, lymph node involvement (Hainsworth et al, 1991) and markers of increased cellular proliferation such as Ki-67 (Toi et al, 1990). It has also been shown to be significantly associated with resistance to hormone therapy , reduced relapse-free period (Lewis et al, 1990;Nicholson et al, 1990) and reduced overall survival .…”

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confidence: 99%

“…ER is immunolocalised in the nuclei of target cells (King & Green, 1984;King et al, 1985), and human breast cancer is found to have a heterogeneous population of ER-positive cells and ER-negative cells (King et al, 1985). The EGFR immunocytochemical assay (EGFR-ICA) using the monoclonal antibody EGFR1 (Waterfield et al, 1982) localises EGFR on the cellular membrane and this also displays a heterogeneous distribution (Toi et al, 1989).…”

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