Tamoxifen is indicated for the treatment of breast cancer in a variety of settings. It should be noted that evidence suggests that patients with estrogen receptor positive tumors are more likely to benefit from tamoxifen.[1] Tamoxifen also has many off-labeled uses, and they may require additional data.
FDA-Approved Indications
Non-FDA-Approved Indications
Tamoxifen exhibits both estrogenic agonist and antagonist effects in different parts of the body. Because it has two actions, it is patient-specific as a selective estrogen receptor modulator (SERM). In the breast tissue, it competes with estrogen for binding sites and causes antiestrogenic and antitumor effects. Through downstream intracellular processes, it slows cell cycling which classifies it as cytostatic. In the bone it stimulates estrogen receptors instead of blocking them, exerting an estrogenic agonist effect, and may prevent osteoporosis in postmenopausal women.[37]
Tamoxifen is available in a tablet (10 mg or 20 mg) or an oral solution (10 mg/5 mL). If it as administered as an oral solution, it is important to use the supplied dosing cup for adequate administration. The American Society of Clinical Oncology (ASCO) guidelines for Adjuvant Endocrine Therapy of Hormone-Receptor Positive Breast Cancer recommends a dose of 20 mg daily for breast cancer prevention after completion of chemotherapy. The duration of endocrine therapy depends on the patient's menopausal status and can last 5 to 10 years.[38] For the treatment of metastatic breast cancer, 20 to 40 mg daily is recommended, although clinical benefit has not been shown for doses above 20 mg daily.[39] In some off-label clinical trials, 10 mg was used as the dose. It may be taken with or without food.
Tamoxifen has a black box warning for uterine malignancies, pulmonary embolism, and stroke in patients who are at high risk for cancer or who have ductal carcinoma in situ.[40] In patients who are female, tamoxifen is associated with an increased incidence of uterine or endometrial cancers, with some being fatal. In patients who were already diagnosed with breast cancer, however, the benefits outweigh the risks.[41]
Like many cancer drugs, tamoxifen has many adverse effects associated with it, though serious and fatal ones are rare. The most common adverse effects seen in treatment are hot flashes, irregular periods, and vaginal discharge. Other common adverse effects include peripheral edema, hypertension, mood changes, pain, depression, skin changes and skin rashes, nausea and vomiting, weakness, arthritis, arthralgia, lymphedema, and pharyngitis.
Less common adverse effects may include insomnia, dizziness, headache, weight gain, abdominal pain, diarrhea, indigestion, urinary tract infections, thrombocytopenia, back pain, alopecia, ostealgia, and cataracts among many more. Due to the extensive adverse effects of tamoxifen, it is important for patients to discuss all adverse effects they are experiencing with their doctor.[42]
Tamoxifen can also cause a local disease flare which may lead to increased bone and tumor pain. This can be associated with good tumor response and usually resolves quickly. In patients with bone metastasis, hypercalcemia may occur. If hypercalcemia becomes severe and not manageable, discontinue tamoxifen.[43]
Tamoxifen should not be used in patients with a known allergy to it or any component in its formulation or concomitantly with warfarin. For patients taking tamoxifen for breast cancer risk reduction who are at high risk for breast cancer or with ductal carcinoma in situ, it should be avoided if the patient has a history of deep vein thrombosis (DVT) or pulmonary embolism (PE). In patients that have been diagnosed with breast cancer, the benefits outweigh the risks, but it should still be used in caution in patients with a history of thromboembolic events.
Tamoxifen also has many drug-drug interactions, so a comprehensive medication list in all patients receiving it is vital.[44]
All patients on tamoxifen should have routine lab work including a complete blood count with platelets, serum calcium, and liver function tests. Female patients should monitor for abnormal vaginal bleeding and receive a breast and gynecologic exam at baseline and routinely after. Patients should also watch for signs and symptoms of a DVT or PE.
Other monitoring parameters tend to vary, depending on patient-specific factors. In patients with pre-existing hyperlipidemia, triglycerides and cholesterol should be monitored.[45] Patients on vitamin K antagonists should have their INR and PT checked.[46] Reproductive female patients need a pregnancy test before treatment and should use reliable birth control methods during treatment.[47] Premenopausal women should receive a bone mineral density test. All patients should get an ophthalmic exam if vision problems or cataracts occur.[48]
There is currently no antidote available for tamoxifen.
Interprofessional teamwork and communication provide success for all patients, especially those undergoing cancer treatments. Oncologists should thoroughly evaluate the patient and select an appropriate treatment regimen based on guidelines and patient-specific factors. For example, in estrogen receptor-negative breast cancer, tamoxifen may not be appropriate. Oncology nurses should be aware of the more severe adverse effects tamoxifen may cause and look out for them in their patients, reporting concerns to the clinical team. Pharmacists should assist the clinical team by examining the patient’s current and complete drug regimen and make sure there are no interactions as tamoxifen has many. These are just a few examples, and roles tend to overlap in many different professions, but every healthcare professional provides a vital role that, in turn, benefits the patient greatly. [Level 5]
[1] | Brufsky AM,Dickler MN, Estrogen Receptor-Positive Breast Cancer: Exploiting Signaling Pathways Implicated in Endocrine Resistance. The oncologist. 2018 May [PubMed PMID: 29352052] |
[2] | Eggemann H,Altmann U,Costa SD,Ignatov A, Survival benefit of tamoxifen and aromatase inhibitor in male and female breast cancer. Journal of cancer research and clinical oncology. 2018 Feb [PubMed PMID: 29098396] |
[3] | Gradishar W,Salerno KE, NCCN Guidelines Update: Breast Cancer. Journal of the National Comprehensive Cancer Network : JNCCN. 2016 May [PubMed PMID: 27226503] |
[4] | Staley H,McCallum I,Bruce J, Postoperative Tamoxifen for ductal carcinoma in situ: Cochrane systematic review and meta-analysis. Breast (Edinburgh, Scotland). 2014 Oct [PubMed PMID: 25023044] |
[5] | Sauter ER, Breast Cancer Prevention: Current Approaches and Future Directions. European journal of breast health. 2018 Apr [PubMed PMID: 29774312] |
[6] | Hansmann A,Adolph C,Vogel T,Unger A,Moeslein G, High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors. Cancer. 2004 Feb 1 [PubMed PMID: 14745880] |
[7] | Thigpen T,Brady MF,Homesley HD,Soper JT,Bell J, Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001 Jan 15 [PubMed PMID: 11208827] |
[8] | Fiorica JV,Brunetto VL,Hanjani P,Lentz SS,Mannel R,Andersen W, Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecologic oncology. 2004 Jan [PubMed PMID: 14751131] |
[9] | Boccardo F,Rubagotti A,Battaglia M,Di Tonno P,Selvaggi FP,Conti G,Comeri G,Bertaccini A,Martorana G,Galassi P,Zattoni F,Macchiarella A,Siragusa A,Muscas G,Durand F,Potenzoni D,Manganelli A,Ferraris V,Montefiore F, Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005 Feb 1 [PubMed PMID: 15681525] |
[10] | Steiner AZ,Terplan M,Paulson RJ, Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis. Human reproduction (Oxford, England). 2005 Jun [PubMed PMID: 15845599] |
[11] | Adamopoulos DA,Pappa A,Billa E,Nicopoulou S,Koukkou E,Michopoulos J, Effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in men with idiopathic oligozoospermia. Fertility and sterility. 2003 Oct [PubMed PMID: 14556812] |
[12] | Clarke SC,Schofield PM,Grace AA,Metcalfe JC,Kirschenlohr HL, Tamoxifen effects on endothelial function and cardiovascular risk factors in men with advanced atherosclerosis. Circulation. 2001 Mar 20 [PubMed PMID: 11257075] |
[13] | Hatch KD,Beecham JB,Blessing JA,Creasman WT, Responsiveness of patients with advanced ovarian carcinoma to tamoxifen. A Gynecologic Oncology Group study of second-line therapy in 105 patients. Cancer. 1991 Jul 15 [PubMed PMID: 2070324] |
[14] | Markman M,Iseminger KA,Hatch KD,Creasman WT,Barnes W,Dubeshter B, Tamoxifen in platinum-refractory ovarian cancer: a Gynecologic Oncology Group Ancillary Report. Gynecologic oncology. 1996 Jul [PubMed PMID: 8690289] |
[15] | Dellagrammaticas D,Bryden AA,Collins GN, Regression of metastatic transitional cell carcinoma in response to tamoxifen. The Journal of urology. 2001 May [PubMed PMID: 11342939] |
[16] | Yang CH,Cheng AL,Yeh KH,Yu CJ,Lin JF,Yang PC, High dose tamoxifen plus cisplatin and etoposide in the treatment of patients with advanced, inoperable nonsmall cell lung carcinoma. Cancer. 1999 Aug 1 [PubMed PMID: 10430249] |
[17] | Figueredo A,Arnold A,Goodyear M,Findlay B,Neville A,Normandeau R,Jones A, Addition of verapamil and tamoxifen to the initial chemotherapy of small cell lung cancer. A phase I/II study. Cancer. 1990 May 1 [PubMed PMID: 2164872] |
[18] | Eugster EA,Rubin SD,Reiter EO,Plourde P,Jou HC,Pescovitz OH, Tamoxifen treatment for precocious puberty in McCune-Albright syndrome: a multicenter trial. The Journal of pediatrics. 2003 Jul [PubMed PMID: 12915825] |
[19] | Beguerie JR,Xingzhong J,Valdez RP, Tamoxifen vs. non-tamoxifen treatment for advanced melanoma: a meta-analysis. International journal of dermatology. 2010 Oct [PubMed PMID: 20883410] |
[20] | O'Day SJ,Boasberg PD,Kristedja TS,Martin M,Wang HJ,Fournier P,Cabot M,DeGregorio MW,Gammon G, High-dose tamoxifen added to concurrent biochemotherapy with decrescendo interleukin-2 in patients with metastatic melanoma. Cancer. 2001 Aug 1 [PubMed PMID: 11505406] |
[21] | McClay EF,McClay ME,Monroe L,Baron PL,Cole DJ,O'Brien PH,Metcalf JS,Maize JC, The effect of tamoxifen and cisplatin on the disease-free and overall survival of patients with high risk malignant melanoma. British journal of cancer. 2000 Jul [PubMed PMID: 10883662] |
[22] | McKeage MJ,Lorentzos A,Gore ME, Tamoxifen and chemotherapy for refractory metastatic malignant melanoma. The New England journal of medicine. 1993 Jan 14 [PubMed PMID: 8416433] |
[23] | Ricciardi I,Ianniruberto A, Tamoxifen-induced regression of benign breast lesions. Obstetrics and gynecology. 1979 Jul [PubMed PMID: 377165] |
[24] | Taetle R,Mendelsohn J,Green MR, Hypercalcemia and tamoxifen readministered. Annals of internal medicine. 1978 Aug [PubMed PMID: 677600] |
[25] | Moertel CG,Engstrom PF,Schutt AJ, Tamoxifen therapy for metastatic carcinoid tumor: a negative study. Annals of internal medicine. 1984 Apr [PubMed PMID: 6200021] |
[26] | Cvancara JL,Meffert JJ,Elston DM, Estrogen-sensitive cutaneous polyarteritis nodosa: response to tamoxifen. Journal of the American Academy of Dermatology. 1998 Oct [PubMed PMID: 9777776] |
[27] | Fraser IS, Menorrhagia due to myometrial hypertrophy: treatment with tamoxifen. Obstetrics and gynecology. 1987 Sep [PubMed PMID: 3627613] |
[28] | Markwalder TM,Seiler RW,Zava DT, Antiestrogenic therapy of meningiomas--a pilot study. Surgical neurology. 1985 Sep [PubMed PMID: 4023903] |
[29] | Serels S,Melman A, Tamoxifen as treatment for gynecomastia and mastodynia resulting from hormonal deprivation. The Journal of urology. 1998 Apr [PubMed PMID: 9507867] |
[30] | Fentiman IS,Caleffi M,Hamed H,Chaudary MA, Dosage and duration of tamoxifen treatment for mastalgia: a controlled trial. The British journal of surgery. 1988 Sep [PubMed PMID: 3052691] |
[31] | Grio R,Cellura A,Geranio R,Porpiglia M,Piacentino R, [Clinical efficacy of tamoxifen in the treatment of premenstrual mastodynia]. Minerva ginecologica. 1998 Mar [PubMed PMID: 9595924] |
[32] | Li CP,Lee FY,Hwang SJ,Chang FY,Lin HC,Kuo BI,Chu CJ,Lee SD, Treatment of mastalgia with tamoxifen in male patients with liver cirrhosis: a randomized crossover study. The American journal of gastroenterology. 2000 Apr [PubMed PMID: 10763958] |
[33] | Kristensen B,Ejlertsen B,Dalgaard P,Larsen L,Holmegaard SN,Transbøl I,Mouridsen HT, Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: a randomized study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1994 May [PubMed PMID: 8164053] |
[34] | Taçyildiz N,Yavuz G,Unal E,Gündüz K,Günalp I,Ekinci C, Encouraging result of tamoxifen in a retinoblastoma patient with central nervous system metastasis. Pediatric hematology and oncology. 2003 Sep [PubMed PMID: 14631622] |
[35] | De M,Jaap A,Dempster J, Tamoxifen therapy in steroid resistant Reidel's thyroiditis. Scottish medical journal. 2001 Apr [PubMed PMID: 11394342] |
[36] | Lissoni P,Paolorossi F,Tancini G,Ardizzoia A,Barni S,Brivio F,Maestroni GJ,Chilelli M, A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients. British journal of cancer. 1996 Nov [PubMed PMID: 8912546] |
[37] | Lee WL,Cheng MH,Chao HT,Wang PH, The role of selective estrogen receptor modulators on breast cancer: from tamoxifen to raloxifene. Taiwanese journal of obstetrics [PubMed PMID: 18400579] |
[38] | 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, 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 : official journal of the American Society of Clinical Oncology. 2014 Jul 20 [PubMed PMID: 24868023] |
[39] | Bratherton DG,Brown CH,Buchanan R,Hall V,Kingsley Pillers EM,Wheeler TK,Williams CJ, A comparison of two doses of tamoxifen (Nolvadex) in postmenopausal women with advanced breast cancer: 10 mg bd versus 20 mg bd. British journal of cancer. 1984 Aug [PubMed PMID: 6380554] |
[40] | Hernandez RK,Sørensen HT,Pedersen L,Jacobsen J,Lash TL, Tamoxifen treatment and risk of deep venous thrombosis and pulmonary embolism: a Danish population-based cohort study. Cancer. 2009 Oct 1 [PubMed PMID: 19569248] |
[41] | Fisher B,Costantino JP,Redmond CK,Fisher ER,Wickerham DL,Cronin WM, Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. Journal of the National Cancer Institute. 1994 Apr 6 [PubMed PMID: 8133536] |
[42] | Yang G,Nowsheen S,Aziz K,Georgakilas AG, Toxicity and adverse effects of Tamoxifen and other anti-estrogen drugs. Pharmacology [PubMed PMID: 23711794] |
[43] | Mulvenna PM,Wright AJ,Podd TJ, Life-threatening tamoxifen-induced hypercalcaemia. Clinical oncology (Royal College of Radiologists (Great Britain)). 1999 [PubMed PMID: 10465476] |
[44] | Antunes MV,Timm TA,de Oliveira V,Staudt DE,Raymundo S,Gössling G,Biazús JV,Cavalheiro JA,Rosa DD,Wallemacq P,Haufroid V,Linden R,Schwartsmann G, Influence of CYP2D6 and CYP3A4 Phenotypes, Drug Interactions, and Vitamin D Status on Tamoxifen Biotransformation. Therapeutic drug monitoring. 2015 Dec [PubMed PMID: 25853922] |
[45] | Singh HK,Prasad MS,Kandasamy AK,Dharanipragada K, Tamoxifen-induced hypertriglyceridemia causing acute pancreatitis. Journal of pharmacology [PubMed PMID: 27127396] |
[46] | Givens CB,Bullock LN,Franks AS, Safety of concomitant tamoxifen and warfarin. The Annals of pharmacotherapy. 2009 Nov [PubMed PMID: 19843839] |
[47] | Barthelmes L,Gateley CA, Tamoxifen and pregnancy. Breast (Edinburgh, Scotland). 2004 Dec [PubMed PMID: 15563850] |
[48] | Paganini-Hill A,Clark LJ, Eye problems in breast cancer patients treated with tamoxifen. Breast cancer research and treatment. 2000 Mar [PubMed PMID: 10845279] |