Personal ViewTamoxifen: a personal retrospective
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An anti-oestrogen to treat breast cancer
The link between hormones and breast cancer has been known throughout the 20th century. However, during the 1950s, when non-steroidal anti-oestrogens were first discovered, research into the regulation of reproduction was fashionable. As a result, a broad view was taken of their clinical utility. There were many possibilities, including contraception, precocious development, habitual abortion, female fertility, menstrual disturbances, menopause, endometriosis, acne, and cancer.
Clomiphene2 was
Adjuvant therapy
Tamoxifen was found to be effective for about 1 year in treating unselected, advanced breast cancer patients, but it was noted that the anti-oestrogen was more likely to be effective in OER-positive disease.26 The first adjuvant studies used 1 year of therapy to avoid early drug resistance, but did not select only OER-positive patients for study. In general, the results did not show a major advantage for tamoxifen, but did show increases in disease-free survival for some women. Unfortunately,
Prevention of breast cancer
The increased use of tamoxifen throughout the world during the 1980s, and its testing in earlier stages of breast cancer, raised the possibility that the drug could be used prophylactically in women at high risk. The strategy of using an anti-oestrogen to prevent breast cancer in such women was suggested 50 years earlier, by Antoine Lacassagne.40 However, the problem was that an anti-oestrogen could have a deleterious effect on a woman's physiology. If oestrogen is necessary to maintain bone
Tamoxifen's legacy
Tamoxifen has established itself as a pioneering drug for the treatment and prevention of breast cancer through the clinical trials process. However, the story does not end there. The results of the laboratory and clinical investigations pointed to other strategies to prevent diseases associated with menopause. The fact that only half the women who present with breast cancer have risk factors other than age, suggested that a general strategy to use selective oestrogen receptor modulators to
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Cited by (41)
Recent progress in gold and silver nanoparticle mediated drug delivery to breast cancers
2023, Gold and Silver Nanoparticles: Synthesis and ApplicationsSerendipity in the search for “morning-after pills” led to clomiphene for the induction of ovulation
2020, F and S ScienceCitation Excerpt :To put it in the words of Sir Winston Churchill, in 1942 following the British defeat of the Germans at the Battle of El Alamein in North Africa: “This is not the end, or the beginning of the end, but it is, perhaps, the end of the beginning.” The 60-year saga of the nonsteroidal antiestrogens, which started with Dr. Len Lerner’s clomiphene and the induction of ovulation, evolved to the improbable success of tamoxifen for the treatment and prevention of breast cancer (66–68) and the first true SERM, raloxifene, that emerged from academic research at the University of Wisconsin Comprehensive Cancer Center (49). As with all medical discoveries and changes in the standards of care, the advance required committed and determined individuals to drive the agenda based on irrefutable evidence from translational research (69–85).
Tamoxifen induces a pluripotency signature in breast cancer cells and human tumors
2015, Molecular OncologyCitation Excerpt :Breast cancer is a primary cause of death in females, worldwide. Most breast tumors are ERα positive (∼70%) and therefore therapies targeting ERα are applied, either with selective estrogen receptor modulators (SERMs), such as tamoxifen (Jordan, 2000, 2001a, b, 2006), or through deprivation of locally produced estrogen. However, about half of ERα-positive tumors exhibit intrinsic or rapidly acquire resistance to endocrine treatment.
15 years of The Lancet Oncology
2015, The Lancet OncologyDesign, synthesis and biological evaluation of novel triaryl (Z)-olefins as tamoxifen analogues
2013, Bioorganic and Medicinal Chemistry Letters