Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and men.

[16] Serious side effects include a small increased risk of uterine cancer, stroke, vision problems, and pulmonary embolism.

[24][25] Tamoxifen is used for the treatment of both early and advanced estrogen receptor-positive (ER-positive or ER+) breast cancer in pre- and postmenopausal women.

[29] The effectiveness of tamoxifen is primarily influenced by estrogen receptor (ER) status, which was the key predictor of the proportional benefits observed.

[37][38] Benign enlargement of the male breast, whether asymptomatic or painful, is a common condition thought to result from an increased estrogen/testosterone ratio or from heightened estrogenic or reduced androgenic activity via receptor interactions.Tamoxifen is used to prevent and treat gynecomastia.

[44][45][46] It has been found to decrease growth velocity and the rate of bone maturation in girls with precocious puberty, and hence to improve final height in these individuals.

[14] In dose-ranging studies, tamoxifen was administered at very high doses in women (e.g., 300 mg/m2) and was found to produce acute neurotoxicity including tremor, hyperreflexia, unsteady gait, and dizziness.

Recent research has shown that 7–10% of women with breast cancer may not receive the full medical benefit from taking tamoxifen due to their genetic make-up.

[65] A U.S. study presented at the American Society of Clinical Oncology's annual meeting in 2009 found that after two years, 7.5% of women who took only tamoxifen had a recurrence, compared with 16% who took either paroxetine, fluoxetine or sertraline, drugs considered to be the most potent CYP2D6 inhibitors.

Patients taking the SSRIs Celexa (citalopram), Lexapro (escitalopram), and Luvox (fluvoxamine) did not have an increased risk of recurrence, due to their lack of competitive metabolism for the CYP2D6 enzyme.

Patients treated with both paroxetine and tamoxifen have a 67% increased risk of death from breast cancer, from 24% to 91%, depending on the duration of coadministration.

[92][93] This unusual profile of DRI activity has made tamoxifen of potential interest as a starting point for structural modification to develop novel pharmaceutical drugs for treatment of stimulant use disorder.

[7][94] High concentrations of tamoxifen have been found in breast, uterus, liver, kidney, lung, pancreas, and ovary tissue in animals and humans.

[104] In the late 1950s, pharmaceutical companies were actively researching a newly discovered class of anti-estrogen compounds in the hope of developing a morning-after contraceptive pill.

[20] It was there in 1962 that chemist Dora Richardson first synthesized tamoxifen, back then known as ICI-46,474, when she was looking to create triphenylethylene derivatives for the contraceptive pill project that her team was researching.

[105] This compound was originally created to work as an estrogen inhibitor, but instead was found to stimulate ovulation in participants of the drug testing trial.

[106] Tamoxifen did eventually receive marketing approval as a fertility treatment, but the class of compounds never proved useful in human contraception.

[20] It was only when Walpole threatened to leave his position that corporate decided to allow trials and testing for tamoxifen as a drug that could be used to treat breast cancer.

Without Walpole's effort towards defending the work that his team had done in discovering a possibly revolutionary source for breast cancer treatment, tamoxifen could have become a discarded or under-researched idea.

[19] Tamoxifen is one of three drugs in an anti-angiogenetic protocol developed by Dr. Judah Folkman, a researcher at Children's Hospital at Harvard Medical School in Boston.

[108] Other antiestrogens, such as ethamoxytriphetol (MER-25) and clomifene (MRL-41), were assessed for treatment of breast cancer and found to be effective before tamoxifen, but were plagued with toxicity issues.

[109][110] The first clinical study of tamoxifen took place at the Christie Hospital in 1971, and showed a convincing effect in advanced breast cancer, but nevertheless ICI's development programme came close to termination when it was reviewed in 1972.

The drug was subsequently reinvented from a failed contraceptive, to become tamoxifen, the gold standard for the adjuvant treatment of breast cancer and the pioneering medicine for chemprevention for high-risk women.

1980 saw the publication of the first trial to show that tamoxifen given in addition to chemotherapy improved survival for patients with early breast cancer.

[118] A clinical strategy was described[119] that led to the creation of SERMs as a group of multifunctional medicines aimed at the treatment or prevention of many conditions in postmenopausal women, e.g. osteoporosis and breast cancer.

Shortly after, Dora Richardson published a history of tamoxifen that, unusually for that type of paper, included personal accounts and letters from patients who attributed their healing to the drug.

This testimony from cancer patients using tamoxifen helped to shape and push forward research, by justifying it both morally and scientifically to corporations.

Tamoxifen has been seen to decrease rapid bone maturation which is the result of excessive estrogen and alter predicted adult height (PAH).

[133] While widely used in transgenic research, the strong anabolic effect of tamoxifen on bone might confound this approach, especially as it relates to bone-targeted constructs.

[134][135] As of September 2019[update], endoxifen, a major active metabolite of tamoxifen with a 4-fold more potent PKC inhibition, was in phase III clinical trials for bipolar disorder.