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Natural history of breast cancer: Progression from hyperplasia to neoplasia as predicted by angiogenesis
Author(s) -
Gullino Pietro M.
Publication year - 1977
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(197706)39:6<2697::aid-cncr2820390656>3.0.co;2-4
Subject(s) - medicine , angiogenesis , breast cancer , cancer , metastasis , hyperplasia , pathology , mammary gland , ductal carcinoma , carcinoma in situ , oncology
The age‐adjusted death rate of women with breast cancer has not improved appreciably over the last 20 years. The average duration of life for untreated breast cancer is about three years with a survival rate of about 40% at three years and 18–20% at five years. If the time required for a tumor to double its diameter during a known period of time is taken as a measure of growth rate, one can calculate by extrapolation that two‐thirds of the duration of a breast cancer remains undetectable by the patient or physician. Long before a breast carcinoma can be detected by present technology, metatastic spread may occur and does in most cases. Early removal of the primary lesion is indispensable but not sufficient to prevent metastases. A major task for the biologist is to characterize the preclinical phase of breast cancer, in particular to predict which lesion—morphologically definable only as hyperplastic—already has the potential for unrestrained growth and metastasis. Evidence from our laboratory suggests that progression from hyperplasia to neoplasia can be evaluated by determining whether mammary tissue has acquired the capacity to induce new formation of vessels in the host tissue. The test was done by transplanting tissue fragments onto the iris of rabbits and angiogenesis was evaluated by direct observation through the transparent cornea. Human mammary papillomas and carcinomas, infiltrating or in situ, produced angiogenesis almost constantly, resting mammary tissue almost never, but about 30% of hyperplastic epithelium showed an angiogenic capacity. In the mouse mammary gland, frequency of the angiogenic response increased with the increased frequency of neoplastic transformation of the hyperplastic lesions. In the human mammary gland, the angiogenic capacity of hyperplastic lesions was as frequent as in the mouse gland. Whether the risk of future neoplastic behavior is also similar, should be tested in a prospective clinical trial. A simple method of localizing hyperplastic epithelium can be used for mammary tissue obtained from routine biopsies of “benign” lesions. If the angiogenic property of hyperplastic epithelium can identify a population of women with a mammary parenchyma at higher risk of developing breast carcinoma, a powerful tool is available for predicting neoplastic transformation before clinical manifestations.