Angiogenesis as a marker of preneoplastic lesions of the human breast

At the time of biopsy or mastectomy, 947 tissue fragments from 42 patients were transplanted onto the rabbit iris to determine their capacity to elicit new formation of vessels. In all 10 carcinomas tested, at least 1 of the transplanted fragments induced a strong angiogenic response. Of 50 transplants from hyperplastic lobules, 28% also elicited new vessel formation. Fibrous or adipose tissue and tissues from normal lobules, fibrocystic disease, fibroadenoma, lipoma, and gynecomastia almost always failed to produce angiogenesis (Table 1). In the angiogenesis test the human mammary gland behaves like the mouse gland: a fraction of epithelial lesions, which morphologically appear hyperplastic, is already able to induce an angiogenic response just as the carcinomas. In the mouse, the frequency of neoplastic transformation is higher for those hyperplastic lesions with a high frequency of angiogenic response.13 These results suggest that a major effort may be warranted to ascertain whether the frequency of carcinomas is higher in human subjects whose mammary hyperplastic lesions elicit a strong angiogenic response. The angiogenic assay could distinguish lesions undergoing neoplastic transformation before morphological signs of „atypia”︁ and invasion appear.