World Library  
Flag as Inappropriate
Email this Article


Systematic (IUPAC) name
Clinical data
Trade names Nolvadex, Istubal, Valodex, Genox
  • AU: B3
  • US: D (Evidence of risk)
Legal status
Routes of
Pharmacokinetic data
Protein binding 99%
Metabolism Hepatic (CYP3A4, 2C9 and 2D6)
Biological half-life 5-7 days[1]
Excretion Faeces (65%), urine (9%)
CAS Registry Number  Y
ATC code L02
PubChem CID:
DrugBank  Y
ChemSpider  Y
Chemical data
Formula C26H29NO
Molecular mass 371.515 g/mol
563.638 g/mol (citrate salt)

Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, 4-hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, and thus may be characterized as a selective estrogen-receptor modulator. Tamoxifen is the usual endocrine (anti-estrogen) therapy for hormone receptor-positive breast cancer in pre-menopausal women, and is also a standard in post-menopausal women although aromatase inhibitors are also frequently used in that setting.[2]

Some breast cancer cells require estrogen to grow. Estrogen binds to and activates the estrogen receptor in these cells. Tamoxifen is metabolized into compounds that also bind to the estrogen receptor but do not activate it. Because of this competitive antagonism, tamoxifen acts like a key broken off in the lock that prevents any other key from being inserted, preventing estrogen from binding to its receptor, blocking cancer cell growth.

Tamoxifen was discovered by health system.[4]


  • Medical uses 1
    • Breast cancer 1.1
    • Infertility 1.2
    • Gynecomastia 1.3
    • Other conditions 1.4
  • Mechanism of action 2
  • Side effects 3
    • Bone 3.1
    • Endometrial cancer 3.2
    • Cardiovascular and metabolic 3.3
    • Central nervous system 3.4
    • Premature growth plate fusion 3.5
  • Pharmacogenetics and drug interactions 4
  • Market 5
  • History 6
  • Research 7
    • Riedel's thyroiditis 7.1
    • Bipolar disorder 7.2
    • McCune-Albright syndrome 7.3
  • See also 8
  • References 9
  • External links 10

Medical uses

Breast cancer

Tamoxifen is currently used for the treatment of both early and advanced ER+ (estrogen receptor positive) breast cancer in pre- and post-menopausal women.[5] Additionally, it is the most common hormone treatment for male breast cancer.[6] It is also approved by the FDA for the prevention of breast cancer in women at high risk of developing the disease.[7] It has been further approved for the reduction of contralateral (in the opposite breast) cancer. The use of tamoxifen is recommended for 10 years.[8]

In 2006, the large STAR clinical study concluded that raloxifene is equally effective in reducing the incidence of breast cancer, but after an average 4-year follow-up there were 36% fewer uterine cancers and 29% fewer blood clots in women taking raloxifene than in women taking tamoxifen, although the difference is not statistically significant.[9][10][11]


Tamoxifen is used to treat infertility in women with anovulatory disorders. A dose of 10–40 mg per day is administered in days 3–7 of a woman's cycle.[12]


Tamoxifen is used to prevent estrogen-related gynecomastia, resulting from elevated estrogenic levels. It is taken as a preventative measure in small doses, or used at the onset of any symptoms such as nipple soreness or sensitivity. Other drugs are taken for similar purposes such as clomiphene citrate and the anti-aromatase drugs which are used in order to try to avoid the hormone related adverse effects. Tamoxifen is also sometimes used to treat or prevent gynecomastia in sex offenders undergoing temporary chemical castration.[13]

Other conditions

Occasionally tamoxifen is used in treatment of the rare conditions of retroperitoneal fibrosis[14] and idiopathic sclerosing mesenteritis.[15]

Mechanism of action

Crystallographic structure of 4-hydroxy-tamoxifen (carbon = white, oxygen = red, nitrogen = blue) complexed with ligand binding domain of estrogen receptor alpha (cyan ribbon).[16]

Tamoxifen itself is a prodrug, having relatively little affinity for its target protein, the estrogen receptor. It is metabolized in the liver by the cytochrome P450 isoform CYP2D6 and CYP3A4 into active metabolites such as 4-hydroxytamoxifen (afimoxifene) and N-desmethyl-4-hydroxytamoxifen (endoxifen)[17] which have 30-100 times more affinity with the estrogen receptor than tamoxifen itself. These active metabolites compete with estrogen in the body for binding to the estrogen receptor. In breast tissue, 4-hydroxytamoxifen acts as an estrogen receptor antagonist so that transcription of estrogen-responsive genes is inhibited.[18]

4-hydroxytamoxifen binds to estrogen receptors (ER), the ER/tamoxifen complex recruits other proteins known as co-repressors and then binds to DNA to modulate gene expression. Some of these proteins include NCoR and SMRT.[19] Tamoxifen function can be regulated by a number of different variables including growth factors.[20] Tamoxifen needs to block growth factor proteins such as ErbB2/HER2[21] because high levels of ErbB2 have been shown to occur in tamoxifen resistant cancers.[22] Tamoxifen seems to require a protein PAX2 for its full anticancer effect.[21][23] In the presence of high PAX2 expression, the tamoxifen/estrogen receptor complex is able to suppress the expression of the pro-proliferative ERBB2 protein. In contrast, when AIB-1 expression is higher than PAX2, tamoxifen/estrogen receptor complex upregulates the expression of ERBB2 resulting in stimulation of breast cancer growth.[21][24]

4-Hydroxytamoxifen binds to estrogen receptors competitively (with respect to the endogenous agonist estrogen) in tumor cells and other tissue targets, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects. It is a nonsteroidal agent with potent antiestrogenic properties which compete with estrogen for binding sites in breast and other tissues. Tamoxifen causes cells to remain in the G0 and G1 phases of the cell cycle. Because it prevents (pre)cancerous cells from dividing but does not cause cell death, tamoxifen is cytostatic rather than cytocidal.

The scientific literature is complex with respect to the activity of tamoxifen, and care should be taken to establish whether tamoxifen, or the 4-hydroxy metabolite was used, especially in in vitro assays.

Side effects

A report in September 2009 from Health and Human Services' Agency for Healthcare Research and Quality suggests that tamoxifen, raloxifene, and tibolone used to treat breast cancer significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects.[25]

Some cases of lower-limb lymphedema have been associated with the use of tamoxifen, due to the blood clots and deep vein thrombosis (DVT) that can be caused by this medication. Resolution of the blood clots or DVT is needed before lymphedema treatment can be initiated.


A beneficial side effect of tamoxifen is that it prevents bone loss by acting as an estrogen receptor agonist (i.e., mimicking the effects of estrogen) in this cell type. Therefore, by inhibiting osteoclasts, it prevents osteoporosis.[26][27] When tamoxifen was launched as a drug, it was thought that tamoxifen would act as an estrogen receptor antagonist in all tissue, including bone, and therefore it was feared that it would contribute to osteoporosis. It was therefore very surprising that the opposite effect was observed clinically. Hence tamoxifen's tissue selective action directly led to the formulation of the concept of selective estrogen receptor modulators (SERMs).[28] In contrast tamoxifen appears to be associated with bone loss in premenopausal women who continue to menstruate after adjuvant chemotherapy.[29]

Endometrial cancer

Tamoxifen is a selective estrogen receptor modulator.[30] Even though it is an antagonist in breast tissue it acts as partial agonist on the endometrium and has been linked to endometrial cancer in some women. Therefore endometrial changes, including cancer, are among tamoxifen's side effects.[31] With time, risk of endometrial cancer may be doubled to quadrupled, which is a reason tamoxifen is typically only used for 5 years.[32]

The American Cancer Society lists tamoxifen as a known carcinogen, stating that it increases the risk of some types of uterine cancer while lowering the risk of breast cancer recurrence.[33] The ACS states that its use should not be avoided in cases where the risk of breast cancer recurrence without the drug is higher than the risk of developing uterine cancer with the drug.

Cardiovascular and metabolic

Tamoxifen treatment of postmenopausal women is associated with beneficial effects on serum lipid profiles. However, long-term data from clinical trials have failed to demonstrate a cardioprotective effect.[34] For some women, tamoxifen can cause a rapid increase in triglyceride concentration in the blood. In addition there is an increased risk of thromboembolism especially during and immediately after major surgery or periods of immobility.[35] Tamoxifen is also a cause of fatty liver, otherwise known as steatorrhoeic hepatosis or steatosis hepatis.[36]

Central nervous system

Tamoxifen-treated breast cancer patients show evidence of reduced cognition,[37] a major side effect of tamoxifen, and semantic memory scores.[38] However memory impairment in patients treated with tamoxifen was less severe compared with those treated with anastrozole (an aromatase inhibitor).[39]

A significant number of tamoxifen treated breast cancer patients experience a reduction of libido.[40][41]

Premature growth plate fusion

While tamoxifen has been shown to antagonize the actions of estrogen in tissues such as the breast, its effects in other tissues such as bones has not been documented fully. There have been studies done in mice showing tamoxifen mimic the effects of estrogen on bone metabolism and skeletal growth. Thus increasing the possibility of pre-mature bone fusion. This effect would be less of a concern in adults who have stopped growing.[42]

Pharmacogenetics and drug interactions

Nolvadex (tamoxifen) 20 mg tablets

Patients with variant forms of the gene CYP2D6 (also called simply 2D6) may not receive full benefit from tamoxifen because of too slow metabolism of the tamoxifen prodrug into its active metabolite 4-hydroxytamoxifen.[43][44] On Oct 18, 2006 the Subcommittee for Clinical Pharmacology recommended relabeling tamoxifen to include information about this gene in the package insert.[45]

Certain CYP2D6 variations in breast cancer patients leads to a worse clinical outcome for tamoxifen treatment.[46] Genotyping therefore has the potential for identification of women who have these CYP2D6 phenotypes and for whom the use of tamoxifen is associated with poor outcomes.

Recent studies suggest that taking the selective serotonin reuptake inhibitors (SSRIs) antidepressants paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft) can decrease the effectiveness of tamoxifen, as these drugs compete for the CYP2D6 enzyme which is needed to metabolize tamoxifen into the active form, endoxifen.[47] A U.S. study presented at the American Society of Clinical Oncology's annual meeting in 2009 found that after two years, 7.5 percent of women who took only tamoxifen had a recurrence, compared with 16 percent who took either paroxetine, fluoxetine or sertraline, drugs considered to be the most potent CYP2D6 inhibitors. That difference translates to a 120 percent increase in the risk of breast cancer recurrence. 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.[48] A newer study demonstrated a clearer and stronger effect from paroxetine in causing the worst outcomes. 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.[49]

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 unique genetic make-up. DNA Drug Safety Testing can examine DNA variations in the CYP2D6 and other important drug processing pathways. More than 20% of all clinically used medications are metabolized by CYP2D6 and knowing the CYP2D6 status of a person can help the doctor with the future selection of medications.[50] Other molecular biomarkers may also be used to select appropriate patients likely to benefit from tamoxifen.[51]


Global sales of tamoxifen in 2001 were $1,024 million.[52] Since the expiration of the patent in 2002, it is now widely available as a generic drug around the world. As of 2004, tamoxifen was the world's largest selling hormonal drug for the treatment of breast cancer.[53]


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. Arthur L Walpole was a reproductive endocrinologist who led such a team at the Alderley Park research laboratories of ICI Pharmaceuticals. It was there in 1966 that Dora Richardson first synthesised tamoxifen, known then as ICI-46,474.[54] Walpole and his colleagues filed a UK patent covering this compound in 1962, but patent protection on this compound was repeatedly denied in the US until the 1980s.[55] Tamoxifen did eventually receive marketing approval as a fertility treatment, but the class of compounds never proved useful in human contraception. A link between estrogen and breast cancer had been known for many years, but cancer treatments were not a corporate priority at the time, and Walpole's personal interests were important in keeping support for the compound alive in the face of this and the lack of patent protection.[3]

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. Folkman discovered in the 1970s that angiogenesis – the growth of new blood vessels – plays a significant role in the development of cancer. Since his discovery, an entirely new field of cancer research has developed. Clinical trials on angiogenesis inhibitors have been underway since 1992 using myriad different drugs. The Harvard researchers developed a specific protocol for a golden retriever named Navy who was cancer-free after receiving the prescribed cocktail of celecoxib, doxycycline, and tamoxifen – the treatment subsequently became known as the Navy Protocol.[56] Furthermore tamoxifen treatment alone has been shown to have anti-angiogenetic effects in animal models of cancer which appear to be, at least in part, independent of tamoxifen's estrogen receptor antagonist properties.[57]

The first clinical study took place at the Christie Hospital in 1971, and showed a convincing effect in advanced breast cancer,[58] but nevertheless ICI's development programme came close to termination when it was reviewed in 1972. Tamoxifen's further development may have been bolstered by a second clinical study by Harold W.C. Ward [59] at the Queen Elizabeth Hospital, Birmingham. Ward's study showed a more definitive response to the drug at a higher dosage. Walpole also may have helped to convince the company to market tamoxifen for late stage breast cancer in 1973.[55] He was also instrumental in funding V. Craig Jordan to work on tamoxifen. In 1972, ICI Pharmaceuticals Division abandoned development of tamoxifen for financial reasons. 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.[60] Two books, Estrogen Action, Selective Estrogen Receptor Modulators and Women's Health (Imperial College Press 2013) and Tamoxifen Pioneering Medicine in Breast Cancer (Springer 2013) tell this story.

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.[61] In advanced disease, tamoxifen is now only recognised as effective in estrogen receptor positive (ER+) patients, but the early trials did not select ER+ patients, and by the mid 1980s the clinical trial picture was not showing a major advantage for tamoxifen.[62] Nevertheless, tamoxifen had a relatively mild side-effect profile, and a number of large trials continued.

The pharmacology of SERMs was discovered, defined, and deciphered during the 1980s [63] A clinical strategy was described [64] 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. This story is told in: V. Craig Jordan, ed. 2013. "Estrogen Action, Selective Estrogen Receptor Modulators and Women's Health" Imperial College Press, Singapore.

It was not until 1998 that the meta-analysis of the Oxford based Early Breast Cancer Trialists' Collaborative Group showed definitively that tamoxifen saved lives in early breast cancer.[65]


Tamoxifen is used as a research tool to trigger tissue-specific gene expression in many conditional expression constructs in genetically modified animals including a version of the Cre-Lox recombination technique.[66]

The drug has also been studied in several additional indications.

Riedel's thyroiditis

Tamoxifen has been proposed as part of a treatment plan for Riedel's thyroiditis.[67]

Bipolar disorder

Tamoxifen has been shown to be effective in the treatment of mania in patients with bipolar disorder by blocking protein kinase C (PKC), an enzyme that regulates neuron activity in the brain. Researchers believe PKC is over-active during the mania in bipolar patients.[68][69]

McCune-Albright syndrome

In McCune-Albright syndrome (MAS) tamoxifen has been used to treat premature puberty and the consequences of premature puberty. Tamoxifen has been seen to decrease rapid bone maturation which is the result of excessive estrogen and alter predicted adult height (PAH).[70][71] The same effects have also been seen in short pubertal boys.[72]

However, one in vitro study in 2007 and later an in vivo study in 2008 have shown that tamoxifen induces apoptosis in growth plate chondrocytes, reduces serum IGF-I levels and causes persistent retardation of longitudinal and cortical radial bone growth in young male rats, leading the researches to express concern giving tamoxifen to growing individuals.[73][74]

See also


  1. ^ "Tamoxifen". 
  2. ^ Mouridsen H, Giobbie-Hurder A, Goldhirsch A, Thürlimann B, Paridaens R, Smith I, Mauriac L, Forbes J, Price KN, Regan MM, Gelber RD, Coates AS (Aug 2009). "Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer". The New England Journal of Medicine 361 (8): 766–76.  
  3. ^ a b Jordan VC (Jan 2006). "Tamoxifen (ICI46,474) as a targeted therapy to treat and prevent breast cancer". British Journal of Pharmacology. 147 Suppl 1 (Suppl 1): S269–76.  
  4. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  5. ^ Jordan VC (Oct 1993). "Fourteenth Gaddum Memorial Lecture. A current view of tamoxifen for the treatment and prevention of breast cancer". British Journal of Pharmacology 110 (2): 507–17.  
  6. ^ "Breast cancer in men". CancerHelp UK. Cancer Research UK. 2007-09-28. Retrieved 2009-03-22. 
  7. ^ Center for Drug Evaluation and Research (July 7, 2005). "Tamoxifen Information: reducing the incidence of breast cancer in women at high risk". U.S. Food and Drug Administration. Archived from the original on June 19, 2007. Retrieved July 3, 2007. 
  8. ^ Burstein HJ, Temin S, Anderson H, Buchholz TA, Davidson NE, Gelmon KE, Giordano SH, Hudis CA, Rowden D, Solky AJ, Stearns V, Winer EP, Griggs JJ (Jul 2014). "Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update". Journal of Clinical Oncology 32 (21): 2255–69.  
  9. ^ National Cancer Institute (2006-04-26). "Study of Tamoxifen and Raloxifene (STAR) Trial". U.S. National Institutes of Health. Retrieved July 3, 2007. 
  10. ^ University of Pittsburgh. "STAR Study of Tamoxifen and Raloxifen". Archived from the original on June 11, 2007. Retrieved July 3, 2007. 
  11. ^ Dr  
  12. ^ Steiner AZ, Terplan M, Paulson RJ (Jun 2005). "Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis". Human Reproduction 20 (6): 1511–5.  
  13. ^ Sample, Ian (2007-06-13). "Q&A: Chemical castration".  
  14. ^ van Bommel EF, Hendriksz TR, Huiskes AW, Zeegers AG (Jan 2006). "Brief communication: tamoxifen therapy for nonmalignant retroperitoneal fibrosis". Annals of Internal Medicine 144 (2): 101–6.  
  15. ^ Akram S, Pardi DS, Schaffner JA, Smyrk TC (May 2007). "Sclerosing mesenteritis: clinical features, treatment, and outcome in ninety-two patients". Clinical Gastroenterology and Hepatology 5 (5): 589–96; quiz 523–4.  
  16. ^ ​; Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL (December 1998). "The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen". Cell 95 (7): 927–37.  
  17. ^ Desta Z, Ward BA, Soukhova NV, Flockhart DA (Sep 2004). "Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6". The Journal of Pharmacology and Experimental Therapeutics 310 (3): 1062–75.  
  18. ^ Wang DY, Fulthorpe R, Liss SN, Edwards EA (Feb 2004). "Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1". Molecular Endocrinology 18 (2): 402–11.  
  19. ^ Shang Y, Hu X, DiRenzo J, Lazar MA, Brown M (Dec 2000). "Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription". Cell 103 (6): 843–52.  
  20. ^ Massarweh S, Osborne CK, Creighton CJ, Qin L, Tsimelzon A, Huang S, Weiss H, Rimawi M, Schiff R (Feb 2008). "Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function". Cancer Research 68 (3): 826–33.  
  21. ^ a b c Hurtado A, Holmes KA, Geistlinger TR, Hutcheson IR, Nicholson RI, Brown M, Jiang J, Howat WJ, Ali S, Carroll JS (Dec 2008). "Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen". Nature 456 (7222): 663–6.  
  22. ^ Osborne CK, Bardou V, Hopp TA, Chamness GC, Hilsenbeck SG, Fuqua SA, Wong J, Allred DC, Clark GM, Schiff R (Mar 2003). "Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer". Journal of the National Cancer Institute 95 (5): 353–61.  
  23. ^ "New Mechanism Predicts Tamoxifen Response: PAX2 gene implicated in tamoxifen-induced inhibition of ERBB2/HER2-mediated tumor growth". 2008-11-13. Retrieved 2008-11-14. 
  24. ^ "Study sheds new light on tamoxifen resistance". News. CORDIS News. Retrieved 2008-11-14. 
  25. ^ OncoGenetics.Org (September 2009). "Medications Effective in Reducing Risk of Breast Cancer But Increase Risk of Adverse Effects". OncoGenetics.Org. Retrieved 2009-09-14. 
  26. ^ Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y, Nishina H, Takeda S, Takayanagi H, Metzger D, Kanno J, Takaoka K, Martin TJ, Chambon P, Kato S (Sep 2007). "Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts". Cell 130 (5): 811–23.  
  27. ^ Krum SA, Miranda-Carboni GA, Hauschka PV, Carroll JS, Lane TF, Freedman LP, Brown M (Feb 2008). "Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival". The EMBO Journal 27 (3): 535–45.  
  28. ^ Mincey BA, Moraghan TJ, Perez EA (Aug 2000). "Prevention and treatment of osteoporosis in women with breast cancer". Mayo Clinic Proceedings 75 (8): 821–9.  
  29. ^ Vehmanen L, Elomaa I, Blomqvist C, Saarto T (Feb 2006). "Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status". Journal of Clinical Oncology 24 (4): 675–80.  
  30. ^ Gallo MA, Kaufman D (Feb 1997). "Antagonistic and agonistic effects of tamoxifen: significance in human cancer". Seminars in Oncology 24 (1 Suppl 1): S1–71–S1–80.  
  31. ^ Grilli S (2006). "Tamoxifen (TAM): the dispute goes on" (PDF). Annali Dell'Istituto Superiore Di Sanità 42 (2): 170–3.  
  32. ^ "Tamoxifen for Breast Cancer & Side Effects". Health and Life. 
  33. ^ "Known and Probable Carcinogens". American Cancer Society. 2006-02-03. Retrieved 2008-03-21. 
  34. ^ Esteva FJ, Hortobagyi GN (Jun 2006). "Comparative assessment of lipid effects of endocrine therapy for breast cancer: implications for cardiovascular disease prevention in postmenopausal women". Breast 15 (3): 301–12.  
  35. ^ Decensi A, Maisonneuve P, Rotmensz N, Bettega D, Costa A, Sacchini V, Salvioni A, Travaglini R, Oliviero P, D'Aiuto G, Gulisano M, Gucciardo G, del Turco MR, Pizzichetta MA, Conforti S, Bonanni B, Boyle P, Veronesi U (Feb 2005). "Effect of tamoxifen on venous thromboembolic events in a breast cancer prevention trial". Circulation 111 (5): 650–6.  
  36. ^ Osman KA, Osman MM, Ahmed MH (Jan 2007). "Tamoxifen-induced non-alcoholic steatohepatitis: where are we now and where are we going?". Expert Opinion on Drug Safety 6 (1): 1–4.  
  37. ^ Paganini-Hill A, Clark LJ (Nov 2000). "Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen". Breast Cancer Research and Treatment 64 (2): 165–76.  
  38. ^ Eberling JL, Wu C, Tong-Turnbeaugh R, Jagust WJ (Jan 2004). "Estrogen- and tamoxifen-associated effects on brain structure and function". NeuroImage 21 (1): 364–71.  
  39. ^ Bender CM, Sereika SM, Brufsky AM, Ryan CM, Vogel VG, Rastogi P, Cohen SM, Casillo FE, Berga SL (2007). "Memory impairments with adjuvant anastrozole versus tamoxifen in women with early-stage breast cancer". Menopause 14 (6): 995–8.  
  40. ^ Mortimer JE, Boucher L, Baty J, Knapp DL, Ryan E, Rowland JH (May 1999). "Effect of tamoxifen on sexual functioning in patients with breast cancer" (abstract). Journal of Clinical Oncology 17 (5): 1488–92.  
  41. ^ Cella D, Fallowfield L, Barker P, Cuzick J, Locker G, Howell A (Dec 2006). "Quality of life of postmenopausal women in the ATAC ("Arimidex", tamoxifen, alone or in combination) trial after completion of 5 years' adjuvant treatment for early breast cancer". Breast Cancer Research and Treatment 100 (3): 273–84.  
  42. ^ Karimian E, Chagin AS, Gjerde J, Heino T, Lien EA, Ohlsson C, Sävendahl L (Aug 2008). "Tamoxifen impairs both longitudinal and cortical bone growth in young male rats". Journal of Bone and Mineral Research 23 (8): 1267–77.  
  43. ^ Goetz MP, Rae JM, Suman VJ, Safgren SL, Ames MM, Visscher DW, Reynolds C, Couch FJ, Lingle WL, Flockhart DA, Desta Z, Perez EA, Ingle JN (Dec 2005). "Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes". Journal of Clinical Oncology 23 (36): 9312–8.  
  44. ^ Beverage JN, Sissung TM, Sion AM, Danesi R, Figg WD (Sep 2007). "CYP2D6 polymorphisms and the impact on tamoxifen therapy". Journal of Pharmaceutical Sciences 96 (9): 2224–31.  
  45. ^ Information about CYP2D6 and tamoxifen from DNADirect's website
  46. ^ Schroth W, Goetz MP, Hamann U, Fasching PA, Schmidt M, Winter S, Fritz P, Simon W, Suman VJ, Ames MM, Safgren SL, Kuffel MJ, Ulmer HU, Boländer J, Strick R, Beckmann MW, Koelbl H, Weinshilboum RM, Ingle JN, Eichelbaum M, Schwab M, Brauch H (Oct 2009). "Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen". Jama 302 (13): 1429–36.  
  47. ^ Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA (Jan 2005). "CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment". Journal of the National Cancer Institute 97 (1): 30–9.  
  48. ^ Staff Reports (Summer 2009). "ASCO Updates: Antidepressants Reduce the Effectiveness of Tamoxifen.". CURE (Cancer Updates, Research and Education). 
  49. ^ Kelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, Paszat LF. "Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study". BMJ 340: c693.  
  50. ^ Information about Tamoxitest and how DNA testing can help in the selection of the best treatment methodology from Genelex's website
  51. ^ Criscitiello C, Fumagalli D, Saini KS, Loi S (2011). "Tamoxifen in early-stage estrogen receptor-positive breast cancer: overview of clinical use and molecular biomarkers for patient selection". OncoTargets and Therapy 4: 1–11.  
  52. ^ "Cancer the generic impact". BioPortfolio Limited. Archived from the original on 2008-05-16. Retrieved 2008-11-14. 
  53. ^ Vose B. "AstraZenecain Cancer: Slide #15:" (PDF). AstraZeneca Annual Business Review. Retrieved 2009-03-28. 2004 tamoxifen market share: 70% Source: IMS HEALTH, IMS MIDAS Monthly. July 2004. Aromatase Inhibitors + Tamoxifen 
  54. ^ Sneader W (2005). Drug Discovery: A History. New York: Wiley. p. 472 pages.  
  55. ^ a b Jordan VC (Mar 2003). "Tamoxifen: a most unlikely pioneering medicine". Nature Reviews. Drug Discovery 2 (3): 205–13.  
  56. ^ Kirk E (2002-07-24). "Dog's tale of survival opens door in cancer research". Health and Behavior. USA Today. Retrieved 2008-06-24. 
  57. ^ Blackwell KL, Haroon ZA, Shan S, Saito W, Broadwater G, Greenberg CS, Dewhirst MW (Nov 2000). "Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models". Clinical Cancer Research 6 (11): 4359–64.  
  58. ^ Cole MP, Jones CT, Todd ID (Jun 1971). "A new anti-oestrogenic agent in late breast cancer. An early clinical appraisal of ICI46474". British Journal of Cancer 25 (2): 270–5.  
  59. ^ Ward HW (Jan 1973). "Anti-oestrogen therapy for breast cancer: a trial of tamoxifen at two dose levels". British Medical Journal 1 (5844): 13–4.  
  60. ^
  61. ^ Baum M, Brinkley DM, Dossett JA, McPherson K, Patterson JS, Rubens RD, Smiddy FG, Stoll BA, Wilson A, Lea JC, Richards D, Ellis SH (Aug 1983). "Improved survival among patients treated with adjuvant tamoxifen after mastectomy for early breast cancer". Lancet 2 (8347): 450.  
  62. ^ Furr BJ, Jordan VC (1984). "The pharmacology and clinical uses of tamoxifen". Pharmacology & Therapeutics 25 (2): 127–205.  
  63. ^ Jordan VC (Aug 2001). "Selective estrogen receptor modulation: a personal perspective". Cancer Research 61 (15): 5683–7.  
  64. ^ Lerner LJ, Jordan VC (Jul 1990). "Development of antiestrogens and their use in breast cancer: eighth Cain memorial award lecture". Cancer Research 50 (14): 4177–89.  
  65. ^ Early Breast Cancer Trialists' Collaborative Group (May 1998). "Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group". Lancet 351 (9114): 1451–67.  
  66. ^ Feil R, Brocard J, Mascrez B, LeMeur M, Metzger D, Chambon P (Oct 1996). "Ligand-activated site-specific recombination in mice". Proceedings of the National Academy of Sciences of the United States of America 93 (20): 10887–90.  
  67. ^ Dabelic N, Jukic T, Labar Z, Novosel SA, Matesa N, Kusic Z (Apr 2003). "Riedel's thyroiditis treated with tamoxifen" (PDF). Croatian Medical Journal 44 (2): 239–41.  
  68. ^ "Manic Phase of Bipolar Disorder Benefits from Breast Cancer Medication".  
  69. ^ Yildiz A, Guleryuz S, Ankerst DP, Ongür D, Renshaw PF (Mar 2008). "Protein kinase C inhibition in the treatment of mania: a double-blind, placebo-controlled trial of tamoxifen". Archives of General Psychiatry 65 (3): 255–63.  
  70. ^ Eugster EA, Shankar R, Feezle LK, Pescovitz OH (1999). "Tamoxifen treatment of progressive precocious puberty in a patient with McCune-Albright syndrome". Journal of Pediatric Endocrinology & Metabolism 12 (5): 681–6.  
  71. ^ Eugster EA, Rubin SD, Reiter EO, Plourde P, Jou HC, Pescovitz OH (Jul 2003). "Tamoxifen treatment for precocious puberty in McCune-Albright syndrome: a multicenter trial". The Journal of Pediatrics 143 (1): 60–6.  
  72. ^ Kreher NC, Eugster EA, Shankar RR (Dec 2005). "The use of tamoxifen to improve height potential in short pubertal boys". Pediatrics 116 (6): 1513–5.  
  73. ^ Chagin AS, Karimian E, Zaman F, Takigawa M, Chrysis D, Sävendahl L (May 2007). "Tamoxifen induces permanent growth arrest through selective induction of apoptosis in growth plate chondrocytes in cultured rat metatarsal bones". Bone 40 (5): 1415–24.  
  74. ^ Karimian E, Chagin AS, Gjerde J, Heino T, Lien EA, Ohlsson C, Sävendahl L (Aug 2008). "Tamoxifen impairs both longitudinal and cortical bone growth in young male rats". Journal of Bone and Mineral Research 23 (8): 1267–77.  

External links

  • Tamoxifen on OpenWetWare, a life scientist wiki
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.