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Jordan VC
Successful translation research with selective oestrogen receptor modulators to treat and prevent breast cancer
Geburtshilfe Und Frauenheilkunde (2007) 67:443-450.
Thirty years ago, antiestrogen therapy with tamoxifen played only a secondary role in breast cancer care. All hopes to cure metastatic breast cancer were still pinned on either the discovery of new cytotoxic drugs or a dose dense combination of available cytotoxic drugs with bone marrow transplantation. A similar strategy with combination chemotherapy was employed as an adjuvant for primary breast cancer. Simply stated, the goal was to kill the cancer with nonspecific cytotoxic drugs while keeping the patient alive with supportive care. However, medical research does not travel in straight lines and alternative approaches emerged to solve the problem of controlling tumour growth with minimal side effects. The approach was targeted therapy. All the elements of the new strategy were in place twenty years ago supported by scientific principles derived from laboratory research. The approach of using long-term antihormone therapy to control early stage breast cancer growth would revolutionise cancer care by targeting the tumour oestrogen receptor (OER). The success of the strategy would be evidenced by lives saved and contribute to a decrease in the national mortality figures for breast cancer. More importantly, translational research that targeted the tumour OER with a range of new antioestrogenic drugs (aromatase inhibitors, pure antioestrogens) would presage the current fashion of blocking survival pathways for the tumour by developing novel targeted treatments. But a surprise was in store when the pharmacology of "antioestrogens" was studied in detail. The nonsteroidal "antioestrogens" are selective oestrogen modulators (SERMs). In other words, the compounds are antioestrogens in the breast, oestrogens in the bone and lower circulating cholesterol. This knowledge would establish a practical approach to breast cancer chemoprevention for both high risk (tamoxifen) and low risk (raloxifene) women.
Publication Date: 2007-05-01.
Last updated on Wednesday, June 03, 2020