Summary Between 1984 and 1990, 94 women presenting to the Edinburgh Breast Unit with operable breast cancer of 4 cm or greater in diameter (T2, T3, NO, Ni, MO) were given preoperative systemic therapy. Initially, all women received hormone therapy, with CHOP (cyclophosphamide 1 g m-2, doxorubicin 50 mg m-2, vincristine 1.4 mg m-2 to a maximum of 2 mg and prednisolone 40 mg per day orally for 5 days) chemotherapy being administered to those who failed to respond by 3 months. After April 1987, first-line hormone therapy was only offered to women with oestrogen receptor (ER)-moderate/-rich (> 20 fmol mg-1 protein) tumours, and CHOP was reserved for those women whose tumours failed to respond to hormone therapy and for those with ER-negative/-poor tumours. Response data have been published previously (Anderson et al, 1991). After a median follow-up of 7.5 years, there is no difference in survival between those women given initial hormone therapy and those given chemotherapy, with neither group having yet reached its median survival. The two key factors that predicted for a poor survival were the number of involved axillary nodes after preoperative systemic therapy (P < 0.00001) and a lack of response to preoperative therapy (P < 0.05). These data suggest that many women with ER-moderate/-rich tumours will have a good prognosis after preoperative hormone therapy alone. However, it is possible to identify, by their post-systemic therapy axillary node status, a group of women who still have an appalling prognosis after preoperative chemotherapy or hormone therapy.

No abstract

Summary The effect of systemic therapy on tumour oestrogen receptor (ER) concentration has been studied in 88 patients with large, operable, primary tumours (total 89) of the breast. In 26 patients, tumour was not available for study on one occasion (usually post-treatment). Forty-five patients were treated initially by endocrine therapy but, of these, 13 who had failed to respond went on to receive chemotherapy also. Seventeen patients with low concentrations of ER (<20 fmol mg-' protein) were treated directly by chemotherapy. Patients underwent an incisional biopsy for confirmation of diagnosis and determination of pre-treatment ER by radioligand binding assay, followed by systemic therapy for 3 months (or 6 months for both endocrine and cytotoxic therapies). Following 3 months of systemic therapy (6 months when patients received both endocrine and cytotoxic therapies), patients proceeded on to mastectomy and axillary lymphnode clearance. When residual tumour was present within the mastectomy specimen, a portion was selected for ER assay by the pathologist.In both pre-and post-treatment specimens, a section was cut from the face of the tissue portion used for receptor analysis, fixed in formol-saline and stained with haematoxylin and eosin to permit histopathological confirmation of the presence of tumour. Twenty-six patients in whom either the pre-or post-treatment specimen contained <10% tumour, as assessed by the pathologist, have been excluded from the Correspondence: R.A. Hawkins.

Summary Forty-three patients with large (> 4cm) but operable carcinoma of the breast have been treated by endocrine manipulation before definitive local surgery. This has allowed the study of the relationship between response to therapy and pretreatment oestrogen receptor (ER) concentration, as measured by a dextrancoated charcoal adsorption method. Premenopausal patients (17) were treated by surgical (4) or medical (13) oophorectomy. Post-menopausal patients (26) received either tamoxifen (10) The likelihood of response to endocrine treatment in patients with metastatic breast carcinoma is related to the concentration of oestrogen receptor (ER) protein within that tumour (McGuire et al., 1975;Brooks et al., 1980;Jensen, 1975;Dao & Nemoto, 1980;Oriana et al., 1987). The value of ER status in predicting benefit from adjuvant endocrine treatment remains controversial. While several studies have demonstrated that only patients with ER-positive tumours have a significant survival advantage (Rose et al., 1985;Fisher et al., 1986;Rutquist et al., 1987;Meakin, 1986;Marshall et al., 1987;Bianco et al., 1988), the Nato trial (Nolvadex Adjuvant Trial Organisation, 1988) with tumours of ER concentration 20 fmol mg-1 cytosol protein or less were given four cycles of the chemotherapeutic regime CHOP (cyclophosphamide 1 g m-2, adriamycin 50mgm -2, vincristine 1.4 mgm-2, prednisolone 40 mg orally 5 days).Patients over 70 years of age, with a history of psychiatric instability or evidence of metastatic disease on clinical, haematological, biochemical or bone scintiscan investigation were excluded from the study. Seventeen patients were premenopausal, 26 were post-menopausal, i.e. more than 1 year since their last menstrual period. Initial assessmentAt initial presentation, tumour size was assessed from both clinical and radiological examination. The mean clinical diameter was calculated from the mean of eight calipermeasured diameters taken at 22.5°axes. An incisional wedge biopsy was performed under general anaesthesia and 0.6cm3 of tumour removed and sent for histological and biochemical evaluation.The determination of oestrogen receptor concentration The ER concentration of the excised tumour specimen was determined using the dextran-coated charcoal adsorption method (Hawkins et al., 1981). In brief, tumour was homogenised in tris-monothioglycerol-glycerol buffer and centrifuged at low speed; portions of tumour extract were incubated at 4°C overnight with eight concentrations of 3H oestradiol + non-radioactive oestradiol (0.031-62.3 nM). After separation of the bound fraction by adsorption with dextran-coated charcoal and scintillation counting, the concentration of receptor sites and dissociation constant of binding were calculated by Scatchard analysis (Scatchard, 1949) using a programmed BBC microcomputer. Protein concentration was determined in a separate portion of each tumour extract by the method of Bradford (Bradford, 1976) using serum albumin as a standard, with five quality controls. Receptor concentration was fi...

Summary Cellular DNA was analysed by flow cytometry in fine needle aspirates (FNA) from both benign and malignant breast lesions in order to determine the feasibility of flow cytometric analysis. In 22 of 26 (84%) benign and 69 of 74 (93%) malignant aspirates, sufficient cells were present to produce good quality DNA histograms. DNA in all 22 benign lesions was diploid. In contrast, of the 69 cancers with sufficient cells for analysis, 40 The method of aspiration has been described previously (Zajicek, 1965), but briefly aspirates were obtained using a 23 gauge needle attached to a 10ml syringe. The lesion was localised with the needle tip and negative pressure applied. Using a gentle pumping action, material was aspirated into the needle, the pressure was released, and the needle withdrawn.Material was expelled onto 4 dry glass slides and smears prepared: 2 were air dried for subsequent May Grunwald Giemsa staining, and 2 were fixed in alcohol for Papanicoulaou staining. All slides were examined by two pathologists and categorised as either malignant, suspicious, benign or acellular (Dixon et al., 1984). A further drop of aspirated material was taken for immunohistochemical assay of the oestrogen receptor. The remainder of the aspirate, which was to be used for flow cytometric analysis, was expelled into 200Il of citrated buffer, rapidly frozen on dry ice, and stored at -40°C until analysed (Vindel0v et al., 1983a