Klin Onkol 1997; 10(2): 43-53.
Besides a time factor, primary genomic instability of cancer, hormonal and immune regulations, anti-cancer therapy may induce genomic changes leading to further diversification of malignant tumors. The rationale for preventing iatrogenic diversification in breast cancer therapy is presented. Analyses of clinical and experimental results suggest that sublethal chemotherapy may be the main inducer of diversity in breast cancer. Primary chemoresistance, insufficient dose intensity and/or dysfunction of apoptosis-regulating genes play a significant role in this process. Estrogens are stimulatory to hormonally-dependent breast cancer. Athough the results of proper adjuvant endocrine treatment are equivalent to those of chemotherapy, the benefits of anti-hormonal therapy are not sufficiently utilized, especially in pre-menopausal women. However, the predictive value of breast cancer hormonal receptors is limited due to their biological heterogeneity and/or variability of estimations. Radiotherapy lacks the diversification effect. Interestingly, the experimental induction of Fas antigen can be shown in a p53-wildtype breast cancer cell line. Surgery may influence the behavior of breast cancer only indirectly by timing the operation into the safer, luteal phase of menstrual cycle. In general, the phenomenon of therapy-induced diversification of breast cancer has to be recognized if we are to reduce the potentially detrimental effects of current oncological treatment modalities.
