Factors associated with mammographic parenchymal patterns.

The relationship between mammographic parenchymal patterns and known risk factors for breast cancer was studied in 5319 consecutive women presenting for breast screening. Using a multivariate analysis, correlations were found in pre-menopausal women between breast size, weight, age at first pregnancy, history of biopsy and history of cyclical breast pain and parenchymal pattern. In post-menopausal women the parenchymal pattern correlates with breast size, weight, weight change, age at first pregnancy, a history of biopsy and a history of breast feeding. The DY pattern correlated with age, breast size, weight, history of biopsy and menopausal status. When pre-menopausal women were considered separately the DY pattern correlated only with weight and breast size.

Particles with properties of retroviruses in monocytes from patients with breast cancer.

An agent with the properties of a retrovirus has been detected regularly in monocytes from patients with breast cancer. In 97% of breast cancer patients the cell-free culture medium (CFCM) in which the monocytes had been cultured possessed reverse transcriptase (RT) activity. In contrast, RT activity was detected in the CFCM from only 11% of age and sex matched controls (p less than 0.0001; Wilcoxon rank sum test). The RT activity was associated with particles having a buoyant density of between 1.165 and 1.18 g/ml, similar to that of retroviruses. Treatment of the samples with non-ionic detergent abolished the peaking of the activity in this fraction. Enveloped particles (100-120 nm in diameter) with a fringed surface resembling murine mammary tumour virus were found on negative-stain electron microscopy in CFCM obtained from patients with breast cancer. Retrovirus-like particles were also observed in the cytoplasm of giant cells formed by monocytes from these patients, and also in macrophages in breast cancer tissue; however, no such particles were detected in the tumour cells. These findings strongly suggest the presence of a retrovirus in the monocytes from patients with breast cancer. The importance of these observations in the pathophysiology of carcinoma of the breast remains to be established.

The effect of tamoxifen and medroxyprogesterone on giant cell formation by monocytes from patients with breast cancer.

Incubation of peripheral blood monocytes from patients with breast cancer under agarose for 6 days at 37 degrees C in a 5% CO2 atmosphere resulted in giant cell formation. This phenomenon appeared to be mediated by retroviruses present in these cells. In this study giant cell formation was investigated in patients with primary stage I and II breast cancer before and 3 months after mastectomy with axillary lymph node clearance. Mastectomy had no significant inhibitory effect on giant cell formation. In vitro incubation of monocytes from patients with breast cancer in the presence of tamoxifen (Nolvadex) resulted in significant inhibition of giant cell formation (P less than 0.000003; paired Student's t-test). In vitro addition of medroxyprogesterone (Farlutal) to monocytes from patients with breast cancer also resulted in significant inhibition of giant cell formation (P less than 0.003: paired Student's t-test). Furthermore, incubation of monocytes from patients treated by mastectomy followed by 3 months treatment with adjuvant tamoxifen, resulted in a significant reduction (P less than 0.00007; paired Student's t-test) in the number of giant cells compared to the same samples tested before the commencement of the treatment. Giant cell formation may be used as a simple test to predicte the response of patients with breast cancer to either tamoxifen or medroxyprogesterone.

Alteration in monocyte function in patients with breast cancer.

Migration, phagocytosis and lysozyme production of peripheral monocytes from 36 patients with breast carcinoma was compared with a group of 36 healthy controls. A significant reduction in monocyte random migration and migration towards a chemotactic agent (P less than 0.001) was observed in patients with breast cancer. Furthermore monocyte phagocytic activity was also significantly decreased (P less than 0.001) in breast cancer patients compared to the controls. In contrast lysozyme production by peripheral monocytes was significantly increased in patients with breast cancer compared to controls (P less than 0.001). The changes in monocyte function in patients with breast carcinoma were not due to abnormal blood biochemistry or to direct continuous serum inhibitors, suggesting that the defect may be intrinsic. This defect in monocyte function may play an important role in the control of malignancies by cellular immune processes.

Glucose metabolism in patients with gastrointestinal malignancy but without excessive weight loss.

Patients with gastrointestinal malignancy demonstrate impaired glucose disposal during steady state hyperglycaemia, 20.5 +/- 1.4 mumol/kg min when compared with controls 28.2 +/- 2.2 mumol/kg min. This appears to be unrelated to antecedent weight loss, but is related to the presence of metastatic spread (P less than 0.05). Insulin response to hyperglycaemia is normal, but analysis of glucose disposal with time suggests insulin resistance as a factor in the causation of impaired glucose disposal. Free fatty acid levels fail to suppress in cancer patients but their role in the causation of insulin resistance remains unclear.

Altered monocyte function in patients with benign breast disease.

Monocyte migration, lysozyme production and phagocytosis was studied in 34 patients with fibroadenosis, 28 patients with fibroadenoma and 48 healthy female controls. In patients with fibroadenosis and fibroadenoma, monocyte migration and phagocytic activity were significantly reduced when compared to controls (P less than 0.001). Conversely, lysozyme production by monocytes from patients with benign breast disease was significantly higher than in controls (P less than 0.001). In 20 patients with benign breast disease, there was no significant difference in monocyte function before and 3 months after operation. The observed impairment of monocyte function in fibroadenosis and fibroadenoma would not appear to be the result of abnormal blood biochemistry or due to a direct serum inhibitor, but is probably related to an intrinsic cellular defect. Further studies are required to evaluate the significance of impaired monocyte function in the pathophysiology of benign breast disease.

The effect of colorectal malignancies on monocyte migration, lysozyme production, and phagocytosis.

Peripheral monocyte migration, phagocytosis and lysozyme production has been investigated in 46 patients with colorectal malignancies. The diagnosis of colorectal carcinoma was based on clinical, radiological, and endoscopic examinations and confirmed histopathologically after removal of the tumour. The results were compared with a group of 36 normal healthy controls. Monocytes from patients with colorectal malignancies displayed reduced migration towards the chemotactic agent (P less than 0.001), random migration (P less than 0.001), and phagocytic activity (P less than 0.01) compared to normal controls. Lysozyme production by monocytes from patients with colorectal malignancies was significantly increased (P less than 0.01) compared to control subjects. The impairment in monocyte function in patients with colorectal carcinoma was not due to direct serum factors or to abnormal blood biochemistry, suggesting that the defect is intrinsic to the monocytes. These results suggest that an impairment in monocyte function may play an important role in the control of malignancies by cellular immune processes.

An analysis of referral patterns from a breast screening unit.

The reasons for referral from a breast screening unit are reviewed, together with the subsequent outcome and biopsy findings. 4.94% of persons attending were referred for assessment in a breast clinic, biopsy being performed on 2.09% with a detection rate of 4.1 cancers per 1000. 24.4% of the cancers were palpable and 36.6% were non-invasive. A rounded ill-defined mass was the commonest mammographic reason for biopsy. Cancer was found in 15.2% of cases with microcalcification. In no case did clinical examination in the screening unit reveal cancer which was not detected on mammography.

Transformation of blood monocytes to giant cells in vitro from patients with breast cancer.

Monocytes from patients with breast cancer and from control subjects were cultured under agarose for 6 days. Giant cell formation occurred in 32 out of the 36 patients with breast cancer (89 per cent). In contrast giant cell formation was only observed in two of the control subjects (6 per cent). Menstruation and menopause had no effect on giant cell formation. Furthermore, under the experimental conditions of this study, it seems unlikely that serum factors, lymphokines or phagocytic stimulators induced giant cell formation. The results therefore, suggest that giant cell formation may be initiated by viruses already present in the monocytes from patients with breast cancer. Further studies are required to confirm this hypothesis and to elucidate the significance of giant cell formation in the pathogenesis of breast cancer.

Giant cell formation by peripheral human monocytes.

Peripheral monocytes from patients with breast carcinoma were incubated in vitro using an under agarose technique. The monocytes were incubated at 37 degrees C in a 5% CO2 atmosphere using a mixture of 0.75% agarose gel in Eagle's medium supplemented with 10% group AB pooled human serum and 50 micrograms/ml zymosan-activated serum. Significant giant cell formation occurred after 6 days incubation and was most marked after 9 days. The optimum pH for giant cell formation was between 7.0 and 7.4. The age of the subject (range 20-50 years), type of coagulant, delay in monocyte separation, storage of the monocyte preparation for up to 24 h at 4 degrees C, and freezing for up to 3 months, had no effect on giant cell formation. No giant cell formation was observed in control subjects.

Characterisation of the under-agarose method for quantifying migration of highly purified human monocytes.

Optimal conditions governing migration towards chemotactic agent (MTCA) and random migration of purified human monocytes under agarose have been determined. These include an incubation period of 20 h, use of blood group AB pooled human serum, 0.75% agarose type I, pH between 6.8 and 7.2 and performance in 35 mm Falcon plastic petri dishes. A discontinuous Percoll density gradient was used to give monocyte purity of 83 +/- 10% and viability 97-99%. The use of highly purified monocytes was found to be essential, as increasing lymphocyte: monocyte ratio caused inhibition of migration.