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The urinary excretion patterns of oestrogen metabolites, including unusual metabolites, were determined by gas chromatography and mass spectrometry for 63 women with advanced breast cancer and 39 normal postmenopausal women. The concentration of total unusual metabolites excreted was found to be an excellent discriminant between breast-cancer patients and controls (P less than 0.0001). Discrimination between responders and non-responders to endocrine therapy was attempted, using several different indices. Of these, the ratio of Classical Oestrogens to Unusual Metabolites (CE/UM) proved a fair discriminant, but the product of this ratio and the oestriol ratio (CE/UM x E3R) was much the best discriminant. This product, termed a Pattern Index, has considerable potential, not only as a discriminant for selecting therapy, but also as a rapid index of patient response to that therapy.

Soluble and nuclear oestrogen receptor status was determined in both the central and peripheral portions of tumour for 37 cases of adenocarcinoma of the endometrium. Of these, 29 had functional receptor in the peripheral biopsy, but only 19 retained functional receptor in the centre. Six of the 10 patients whose tumours showed this difference came from the group of 12 patients who were immediately post-menopausal (4.50 +/- 1.45 y post-menopausal age). Receptor status was not related to tumour classification into histological grades I and II. However, receptor-negative central biopsies were significantly more likely (P less than 0.05) to be Grade III. Early relapse was also related to a receptor-negative central biopsy.

In 101 breast cancer patients, measurement of oestrogen receptor status in multiple biopsies across a tumour reveals a highly significant difference in the proportion of patients remaining either disease-free (P less than 0.04) or alive (P less than 0.005), when those with uniformly receptor positive (++) primary tumours are matched with clinically comparable patients whose tumours were homogeneously receptor negative (--). Mean follow-up time was 85 months. The prognostic value of this discriminant is particularly striking in the 53 patients with involved nodes at presentation. Of these, 13 were (++) and seven remain alive of whom six are disease-free, whereas 24 of the 29 (--) patients are dead. These results further suggest that receptor assay on a single homogenate gives less clinical information than do assays on multiple biopsies across the tumour. For patients with involved nodes, clinical management may best be decided after determination of 'macroheterogeneity'.