Serum adrenal androgens in women with primary operable breast cancer and their relationship with age and body mass index.

Several studies have found elevated levels of adrenal androgens in postmenopausal women and depressed levels in premenopausal women with breast cancer, suggesting a role for adrenal androgens in the aetiology of breast cancer. We have measured serum dehydroepiandrosterone sulphate and androstenedione in 81 women with primary operable breast cancer and 62 age-matched controls. Results showed that serum levels of both adrenal androgens fell significantly with age in women with breast cancer (P=0.003). However, no relationship was observed between serum adrenal androgen levels and body mass index in either women with breast cancer or controls. Dehydroepiandrosterone sulphate levels were elevated in postmenopausal women with breast cancer compared to controls, and this was not due to preoperative stress. No differences were observed in androstenedione levels between premenopausal or postmenopausal women with breast cancer and controls, nor were dehydroepiandrostenedione sulphate levels significantly different between premenopausal women with breast cancer and controls. These results suggest that dehydroepiandrosterone sulphate has a role in the aetiology of postmenopausal breast cancer.

Can breast surgeons read mammograms of symptomatic patients in the one-stop breast clinic?

AIM: To establish how accurate surgeons were when compared to the radiologists in interpreting symptomatic mammograms in one-stop clinics. METHODS: The surgeons were asked to write their opinion on the mammograms which was compared with the radiologists' report. 144 patients were involved in the study and the data were analysed by McNemara's test for paired categorical data. RESULTS AND CONCLUSIONS: Surgeons were accurate in interpreting most of the mammographic findings. However, they underestimated the presence of benign calcification which was statistically significant. Surgeons can, therefore, be involved in double reading of mammograms in symptomatic breast disease patients and improve the sensitivity which has been the case in double reading by radiologists in the breast screening programme.

Automatic needle biopsy in the diagnosis of early breast cancer.

An automatic needle biopsy system, Bioptycut, has been evaluated for use in the outpatient biopsy of 107 patients with suspected operable breast cancer. Of the 107 patients, 96 proved to have malignancy. The sensitivity of the test was 65%, and the specificity 100%. Using a fine gauge needle the sensitivity was originally less than that of Trucut biopsy, but improved results were obtained with more experience.

Immunological analysis of mucin molecules expressed by normal and malignant mammary epithelial cells.

Many existing MAbs raised against the human milk fat globule or against carcinoma cells recognise epitopes on high-molecular-weight glycoproteins. In a comparative ELISA assay a number of these antibodies have been shown to react with an extract of the human milk fat globule. In comparative immunoblots of cultured normal milk cells and breast cell lines, all were found to bind to large molecules which show some variation in molecular weight depending on the cell source. The HMFG-2 antibody, which is widely used in cancer diagnosis, also recognises epitopes on lower-molecular-weight components. In T47D cells these may be as small as 80,000 Mr, and with electron microscopy this cell line can be shown to accumulate HMFG-2-reactive components in the Golgi apparatus. Using an HMFG-2 affinity column we have immunopurified HMFG-2-reactive material from the 2 breast cancer cell lines MCF-7 and T47D and shown that all of the above antibodies react in a solid-phase ELISA with the purified material. In addition to high-molecular-weight components, the immunopurified material was found to contain lower-molecular-weight components including a glycoprotein of 68,000 Mr that was not, however, recognised by the HMFG-2 antibody on a Western blot. We have used this immunopurified material to generate new MAbs. All of these recognise the high-molecular-weight bands seen with the other antibodies, but 2 of them also recognise a band at 68,000 Mr in blots of MCF-7 and T47D. The second-generation antibodies show a spectrum of reactivity on tissues similar to HMFG-2 and one reacts at least as strongly as HMFG-2 with methanol-acetone-fixed sections of breast cancers.

Strategies for the development of monoclonal antibodies for in vivo imaging: their use in the imaging of ovarian carcinoma.

There are a number of strategies that have been used for the development of monoclonal antibodies which recognise tumour associated antigens. These include the use of whole tumour cells or membrane components as the immunogen, and the use of differentiation antigens, for example the human milk fat globule. The monoclonal antibody HMFG-2 was developed using the latter strategy and has been shown to react with a large molecular weight mucin-like molecule which appears to be highly immunogenic in the mouse. The HMFG-2 antibody is proving to be extremely useful in the localisation of ovarian tumours and is being used in a number of clinics. This antibody and its antigen have a number of characteristics which have contributed to its success in imaging ovarian carcinomas, including the repetitive nature of the antigenic epitope and the antibody's affinity.

Monoclonal antibody HMFG-2 retains activity in vivo and binds to high molecular weight components expressed by metastatic breast cancers.

The monoclonal antibody HMFG-2 was raised against components of the human milk fat globule and human milk epithelial cells. It recognizes an epitope on glycoproteins of varying molecular weight; it is tumour-associated and expressed heterogeneously by most breast cancers. An intravenous injection of 131I-labelled HMFG-2 has been given to patients with recurrent cutaneous metastasis from breast carcinomas. Clearance of radioactivity from the plasma was measured and the label was shown to be carried on intact circulating antibody that had the ability to bind in vitro to the specific determinant as expressed by both the patients own tumour and by cultured breast cancer cells. Antibody was found to be associated with biopsy material taken from skin metastases 24 hours after administration of labelled antibody. However, the amount of radioactivity was insufficient for the production of a positive isotopic scan.

Cyclic AMP inhibits the growth of human breast cancer cells in defined medium.

Three well-characterized human breast cancer cell lines, MCF-7, T47D and Cama-1, have been grown in defined medium in the absence of serum. Under these conditions, the growth of these cells was inhibited by a variety of cyclic AMP elevating agents, including cholera toxin, monobutyryl cyclic AMP, bromo-cyclic AMP, prostaglandin E2, and 1-methyl-3-isobutyryl xanthine. This inhibitory effect of cyclic AMP on breast cancer cells contrasts with the stimulation of proliferation induced by elevation of intra-cellular cyclic AMP in normal human mammary epithelial cells. Such a major perturbation of growth control may arise either as a result of malignant change, or may reflect a difference in the differentiation phenotype of normal and malignant human mammary epithelial cells in vitro.

Lymphocele after renal transplantation.

Lymphoceles occurred in 25 of 115 patients after renal transplantation in the Oxford Unit. Signs of obstruction or pressure were produced in 16 of these 25 patients (15%), while nine were detected on a routine ultrasound scan. The 16 symptomatic lymphoceles were treated successfully by aspiration or surgical fenestration into the peritoneal cavity . Of the possible causes examined, diathermy and division of iliac lymphatics seemed to be the most likely reason for this high incidence. Since a technique of ligating or clipping the iliac lymphatics has been adopted, no lymphoceles have occurred in the subsequent 70 transplants.