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

• Treatment of breast cancer in both females and males[2]
• Adjuvant treatment of breast cancer after patients have completed their primary treatment with surgery and radiation[3]
• Treatment of female patients with ductal carcinoma in situ (non-invasive breast cancer) after surgery and radiation to reduce the risk of invasive breast cancer[4]
• Breast cancer risk reduction in certain patients at high risk (5-year risk = 1.67% calculated by the Gail Model).[5]

Non-FDA-Approved Indications

• Treatment of progressive or recurrent desmoid tumors in combination with sulindac[6]
• Treatment of endometrioid histologies that are recurrent, metastatic, or at high-risk[7][8]
• Treatment of primary or secondary gynecomastia along with breast pain associated with it[9]
• Induction of ovulation in the treatment of infertility[10]
• Treatment of oligospermia in combination with testosterone[11]
• Prophylaxis of coronary arteriosclerosis in men with triple vessel[12]
• Treatment of advanced or recurrent ovarian cancer[13][14]
• Treatment of bladder cancer[15]
• Treatment of lung cancer in addition to initial chemotherapy treatment[16][17]
• Treatment of precocious puberty due to McCune-Albright syndrome in females[18]
• Treatment of metastatic malignant melanoma in combination with other agents including carmustine, cisplatin, and dacarbazine[19][20][21][22]
• Treatment of benign mammary dysplasia[23]
• Treatment of bone metastasis[24]
• Treatment of carcinoid tumor [25], 
• Treatment of cutaneous polyarteritis nodosa[26]
• Treatment of hypertrophy of uterus[27]
• Treatment of meningioma[28]
• Treatment of primary breast pain, premenstrual mastodynia, or breast pain that originated from liver cirrhosis[29][30][31][32]
• Prophylaxis of postmenopausal osteoporosis[33]
• Improvement of length and quality of life in patients with retinoblastoma in addition to treatment protocols[34]
• Treatment of Riedel's thyroiditis[35]
• Treatment of solid tumor secondary malignant neoplasms[36]

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]