II. Indications
-
Breast Cancer in post-menopausal women (Estrogen Receptor positive)
- Original recommendations were for 5 year course following Breast Cancer Management
- As of 2013, ten year course is recommended following Breast Cancer Diagnosis
- Breast Cancer recurrence prevention (NNT 27) who extend their Tamoxifen course from 5 to 10 years
- Benefits still outweigh risks of Endometrial Cancer and Venous Thromboembolism
- Davies (2013) Lancet 381(9869):805-16 +PMID: 23219286 [PubMed]
- Breast Cancer Prevention in pre-Menopause or post-Menopause
- Breast Cancer risk >1.66% in 5 years and age over 35 years old
- Higher efficacy than Raloxifene for breast Cancer Prevention
- However also higher Venous Thromboembolism and Endometrial Cancer Risks
- Unlike Tamoxifen, Raloxifene is not approved for pre-menopausal breast Cancer Prevention
III. Contraindications
- Venous Thromboembolism history
- Perioperative period
- Prolonged immobilization (discontinue 72 hours before expected immobilization)
- History of Cerebrovascular Accident (CVA) or Transient Ischemic Attack (TIA)
IV. Mechanism
- See Selective Estrogen Receptor Modulator
- Positive Estrogen effects
- Stimulates bone mineralization
- Improves lipid profile
- Anti-Estrogenic effects
- No Breast stimulation
- No uterine stimulation
V. Dosing
-
Breast Cancer
- Tamoxifen 10 to 20 mg orally twice daily for 5 to 10 years
- Breast Cancer Prevention
- Tamoxifen 20 mg daily for 5 years
VI. Adverse Effects
- Precautions
- Thromboembolism, Uterine Cancer and Cardiovascular Risk are FDA black box warnings
-
Thromboembolism
- Tamoxifen significantly increases risk
- Associated with 4 cases per 1000 women on Tamoxifen for 5 years
-
Endometrial Cancer (risks apply to postmenopausal women)
- Markedly increased risk if used more than 5 years
- Associated with 4 cases per 1000 women on Tamoxifen for 5 years
- Relative Risk for 2 to 5 years of use: 2.0
- Relative Risk for 5 or more years of use: 6.9
-
Hot Flashes
- See Hot Flashes for management
- Avoid symptomatic management with agents contraindicated following Breast Cancer
- Avoid Estrogen and Phytoestrogens
- Avoid Paroxetine and Fluoxetine (see below)
- Other adverse effects
- Alopecia
- Cataracts
- Eye Exam every 1-2 years
- Lab abnormalities
- Hypercalcemia
- Liver Function Test abnormalities
VII. Safety
- Avoid in Lactation
- Avoid in pregnancy
- Use reliable Contraception for at least 2 months after completing Tamoxifen
- Monitoring
VIII. Efficacy
-
Estrogen Receptor Positive Breast Cancer
- Reduces Breast Cancer recurrence (29%)
- Reduces mortality from Breast Cancer (20%)
- Anti-Estrogen
- Reduces Breast Cancer recurrence rate
- Preserves Bone Mineral Density
- Only applies to post-menopausal patients
- Bone Mineral Density decreases if premenopausal
- Lowers Total Cholesterol and LDL Cholesterol
- Only applies to post-menopausal patients
- No effect on lipids if premenopausal
- Reference
IX. Drug Interactions
-
CYP2D6 Inhibitors (e.g. Paroxetine, Fluoxetine, Bupropion)
- May decrease Tamoxifen efficacy (avoid these CYP2D6 Inhibitors in Breast Cancer patients)
- Oral Anticoagulants
- Tamoxifen may effect bleeding risk
X. Resources
Images: Related links to external sites (from Bing)
Related Studies
| tamoxifen (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| TAMOXIFEN 10 MG TABLET | Generic | $0.18 each |
| TAMOXIFEN 20 MG TABLET | Generic | $0.33 each |
Ontology: Tamoxifen (C0039286)
| Definition (CHV) | syntactic hormone used in breast cancer treatment |
| Definition (NCI) | An antineoplastic nonsteroidal selective estrogen receptor modulator (SERM). Tamoxifen competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA. The result is a reduction in DNA synthesis and cellular response to estrogen. In addition, tamoxifen up-regulates the production of transforming growth factor B (TGFb), a factor that inhibits tumor cell growth, and down-regulates insulin-like growth factor 1 (IGF-1), a factor that stimulates breast cancer cell growth. |
| Definition (NCI_NCI-GLOSS) | A drug used to treat certain types of breast cancer in women and men. It is also used to prevent breast cancer in women who have had ductal carcinoma in situ (abnormal cells in the ducts of the breast) and in women who are at a high risk of developing breast cancer. Tamoxifen is also being studied in the treatment of other types of cancer. It blocks the effects of the hormone estrogen in the breast. Tamoxifen is a type of antiestrogen. |
| Definition (CSP) | selective estrogen receptor modulator; it is agonist for bone tissue and cholesterol metabolism but antagonist in mammary and uterine tissues. |
| Definition (MSH) | One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM. |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | D013629 |
| SnomedCT | 373345002, 75959001 |
| LNC | LP18484-3, MTHU003102, LA14344-8 |
| English | tamoxifen, Ethanamine, 2-(4-(1,2-diphenyl-1-butenyl)phenoxy)-N,N-dimethyl-, (Z)-, (Z)-2-[4(1,2-diphenyl-1-butenyl)-phenoxyl]-N,N-dimethylethanamine, Tamoxifen, 1-p-beta-dimethylamino-ethoxyphenyl-trans-1,2-diphenylbut-1-ene, tamoxifen (medication), Tamoxifen [Chemical/Ingredient], TAMOXIFEN, Tamoxifen (product), Tamoxifen (substance), TMX, TAM |
| Swedish | Tamoxifen |
| Czech | tamoxifen |
| Finnish | Tamoksifeeni |
| Russian | TAMOKSIFEN, ICI 46474, ТАМОКСИФЕН |
| Japanese | タモキシフェン |
| Polish | Tamoksyfen |
| Spanish | tamoxifeno (producto), tamoxifeno (sustancia), tamoxifeno, Tamoxifeno |
| French | Tamoxifène |
| German | Tamoxifen |
| Italian | Tamoxifene |
| Portuguese | Tamoxifeno |
