Biochemical study of cyst fluid in human breast cystic disease: a review

To assess the importance of various risk factors for breast cancer in women with benign proliferative breast lesions, we reevaluated 10,366 consecutive breast biopsies performed in women who had presented at three Nashville hospitals. The median duration of follow-up was 17 years for 3303 women, 1925 of whom had proliferative disease. This sample contained 84.4 per cent of the patients originally selected for follow-up. Women having proliferative disease without atypical hyperplasia had a risk of cancer that was 1.9 times the risk in women with nonproliferative lesions (95 per cent confidence interval, 1.2 to 2.9). The risk in women with atypical hyperplasia (atypia) was 5.3 times that in women with nonproliferative lesions (95 per cent confidence interval, 3.1 to 8.8). A family history of breast cancer had little effect on the risk in women with nonproliferative lesions. However, the risk in women with atypia and a family history of breast cancer was 11 times that in women who had nonproliferative lesions without a family history (95 per cent confidence interval, 5.5 to 24). Calcification elevated the cancer risk in patients with proliferative disease. Although cysts alone did not substantially elevate the risk, women with both cysts and a family history of breast cancer had a risk 2.7 times higher than that for women without either of these risk factors (95 per cent confidence interval, 1.5 to 4.6). This study demonstrates that the majority of women (70 per cent) who undergo breast biopsy for benign disease are not at increased risk of cancer. However, patients with a clinically meaningful elevation in cancer risk can be identified on the basis of atypical hyperplasia and a family history of breast cancer.

In 135 primary breast cancers, there was a significant inverse relation between epidermal-growth-factor receptor (EGFR) and oestrogen receptor (ER) status, and a significant association with tumour size and poor differentiation. The relapse-free survival and overall survival were significantly worse for patients with EGFR+ tumours compared with EGFR- tumours. Relapse-free survival and overall survival were also worse for patients with ER- tumours compared with ER+ tumours. Of the 71 ER- patients 28 were EGFR+ and 43 were EGFR-. The relapse-free and overall survival for ER- but EGFR+ patients were significantly worse than for "double-negative" patients. Moreover, relapse-free survival and overall survival for "double-negative" patients were similar to those for ER+ patients. Thus EGFR status divides the ER- population into good and poor prognosis subgroups. The presence of EGFR was the most important variable in the primary tumours for predicting relapse-free and overall survival. Multivariate analysis showed that EGFR status was the most important variable in predicting relapse-free and overall survival in lymph-node-negative patients, and the second most important variable in lymph-node positive patients.

Recently, a potent vasoconstrictor peptide, endothelin (EDT), was isolated from vascular endothelial cells. We examined its effect on rat vascular smooth muscle cells (VSMCs). EDT induced the elevation of intracellular calcium, which was dependent on extracellular calcium and inhibited by a calcium-channel antagonist in a competitive manner. EDT caused a rapid and transient increase in the c-fos and c-myc mRNA levels and stimulated the DNA synthesis of VSMCs in a dose-dependent manner. This effect of EDT on the proliferation of VSMCs might be related to the development of atherosclerosis.