Influence of polyamines on breast cancer biology

More than 200,000 women are diagnosed yearly with breast cancer in the United States. Despite the significant improvement in survival introduced by both adjuvant hormonal therapy (restricted to estrogen receptor-positive tumors) and chemotherapy, approx 40,000 American women still die yearly from this malignancy. Therefore, improved understanding of the steps involved in carcinogenesis, cancer cell proliferation, and tumor progression is of critical importance to develop specifically targeted preventive and therapeutic regimens. The appreciation of the major role played by estrogens in human breast cancer biology has led to the development of effective treatments aimed at blocking either estrogen action with antiestrogens (1) or estrogen biosynthesis with aromatase inhibitors (2). Both classes of compounds represent classical examples of biologically based therapies and have been found to be highly effective in the treatment of advanced disease, in the adjuvant setting and, at least with antiestrogens, in breast cancer prevention (1,2). Unfortunately, these compounds are ineffective in the treatment of tumors that are either already hormone independent at diagnosis (approximately two-thirds of breast cancers) or which have progressed to hormone independence after an initial period of hormone responsiveness. Therefore, considerable effort is being placed in targeting multiple growth factor and other oncogenic signaling pathways whose activation may be responsible for the development of hormone resistance. It is hoped that these treatments may either prevent progression to hormone independence or may induce regression of tumors that have already become hormone resistant.