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Summary More accurate criteria are required for the selection of patients with node-negative breast cancer for systemic adjuvant therapy. Expression of epidermal growth factor receptor (EGFr) has been shown previously to be inversely related to oestrogen receptor (ER) in patients with operable breast cancer and to be associated with a poorer prognosis. Analysis of EGFr and ER was performed on tumour samples from 231 patients with operable breast cancer followed for up to 6 years after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) The histological status of the axillary lymph nodes, specifically the absolute number of nodes involved, remains the most potent prognostic marker for patients with operable breast cancer (Valagussa et al., 1978;Fisher et al., 1983). Tumour recurrence and death due to breast cancer, however, affects a significant proportion of patients with node-negative disease (Fisher et al., 1989c). Recurrence rates of up to 43% and mortality at 10 years of 32% have been reported (Fisher et al., 1989b), suggesting a need for effective adjuvant systemic therapy for selected patients in this supposedly good prognostic subgroup.It is now recognised that there is a need for a marker (or markers) capable of discriminating patients with axillary node-negative disease at high risk of recurrence and death. Tumour oestrogen receptor (ER) content has been proposed but there is disagreement about its value (Cooke et al., 1979;Fisher et al., 1988 Valagussa, 1987).There have been several reports describing the presence of specific, high affinity receptors for epidermal growth factor (EGFr) on membranes prepared from primary human breast carcinoma (Sainsbury et al., 1985;Perez et al., 1984). These studies showed a marked inverse relationship between expression of EGFr and ER. Tumours which overexpressed EGFr were associated with a poor overall prognosis (Sainsbury et al., 1987;Rios et al., 1988) but short follow-up precluded close examination of patient subgroups in particular nodenegative patients. Continued prospective patient follow-up and increased patient numbers now allows examination of the prognostic value of EGFr, particularly in node-negative patients. Patients and methodsTwo hundred and thirty-one consecutive patients with operatable breast cancer and without biochemical or radiological evidence of distant metastases were treated by simple mastectomy (n = 181) or wide local excision and post-operative radiotherapy by external beam and iridium wire implants (n = 50). Level I axillary nodes (behind pectoralis major) were sampled if palpable at surgery (n = 129, 56%). An average of four nodes were sampled and for those with positive nodes an average of three contained metastatic tumour (range 1-8). In patients treated by mastectomy adjuvant radiotherapy was given to the ipsilateral axilla if the nodes were involved. No patient received adjuvant chemotherapy in this study. Forty patients towards the end of the s...

There was a significantly higher proportion of EGFr+ tumours in the endocrine failure group compared with the control population (P<0.001).EGFr status is a marker for rapid early progression on primary endocrine therapy and the development of non-excisional methods of EGFr analysis would allow better directed therapeutic decisions.The anti-oestrogen drug tamoxifen, and the aromatase inhibitor aminoglutethimide, have been extensively tested in metastatic breast cancer with overall objective remission rates of around 30% (Cole & Todd, 1976;Ward, 1973;Murray & Pitt, 1981; Harris et al., 1986a,b). The lack of serious toxicity in the case of tamoxifen has made this a particularly attractive therapy where quality of life was as important as prolongation (Stewart et al., 1980). In advanced disease ER status predicts response to endocrine therapy (Block et al., 1975;McGuire et al., 1975;Roberts et al., 1978).The proportion of patients with ER positive primary breast cancers increases with age such that about 70% of patients over 70 years of age have ER positive tumours (Allegra et al., 1979; Elwood & Godolphin, 1980). These observations may in part account for the relatively good prognosis for some elderly patients with breast cancer.Tamoxifen had proved useful in the treatment of many elderly patients with advanced or metastatic breast cancer (Ingle et al., 1981;Legha et al., 1978). The use of pharmacological endocrine manipulation as the sole treatment of primary operable breast cancer in the elderly has been reported in several small studies (Preece et al., 1982;Hellenberg et al., 1982;Bradbeer, 1985;Allan et al., 1985;Horgan et al., 1986), and in one randomised prospective study (Gazet et al., 1988), to be an alternative to surgery. Steroid receptor status at relapse was not reported in these studies but in one (Allan et al., 1985) the response rate for ER positive tumours was found to be similar to the overall response rate.The use of primary endocrine therapy for many elderly patients with operable breast cancer became our standard practice in mid-1984. However, not all elderly patients will respond to tamoxifen and some relapse rapidly (within 6 months) without any initial control of tumour growth. We have shown previously that EGF receptor status is a strong prognostic factor in primary breast cancer (Sainsbury et al., 1987 EGFr to age, relapse in elderly patients on primary endocrine therapy, and its role in predicting tumour recurrence in elderly patients treated by primary surgery. Patients and methodsFifty-one patients over seventy years and ten in their late sixties with severe intercurrent medical illness or severe psychological aversion to mastectomy who were otherwise considered to have primary operable breast cancer were offered primary endocrine therapy. Patients with proven distant metastases at the time of presentation, as assessed by biochemical and clinical criteria, were excluded from this study.The study population comprised 61 patients. The median age was 77 years (range 64-96) and all patients ...

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