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Annals of Oncology 1:401-407, 1990
© 1990 European Society for Medical Oncology

research-article

The process of malignant progression in human breast cancer

R. Clarke1, R.B. Dickson1 and N. Brünner2

1Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center Washington, USA
2Finsen Laboratory, Copenhagen Denmark

Correspondence to: Robert Clarke, Ph.D.Room S128, Vincent T. Lombardi Cancer Research Center, Georgetown University Medical School, 3800 Reservoir Road N.W.Washington, DC 20007, USA

Malignant progression in breast cancer represents the processes through which localized, hormone-dependent tumor cells become resistant to endocrine manipulations and metastasize to sites distant from the primary tumor. By selection in ovariectomized athymic nude mice, we have isolated a variant (MIII) of the hormone-dependent, poorly invasive, human breast cancer cell line MCF-7. MIII cells have lost their absolute requirement for estrogen to form proliferating tumors in nude mice. Furthermore, these tumors are significantly more invasive than the parental MCF-7 cell line. MIII cells retain some responsivity to estrogens and antiestrogens, indicating that they have progressed to a hormone-independent but hormone-esponsive phenotype. In an attempt to determine the nature of this process, we have compared the phenotype of MIII cells with that of other MCF-7 variants. These comparisons strongly suggest that the factors contributing to perturbations in antiestrogen sensitivity, hormone-dependent growth, metastatic potential and tumorigenicity are essentially independent of each other and acquired in a random manner. Loss of estrogen receptor expression and overexpression of EGF receptors tend to occur later in the process of malignant progression.

breast cancer, malignant progression, hormone dependence


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