Skip to Content

Tamoxifen Citrate

Class: Estrogen Agonists-Antagonists
VA Class: AN500
Chemical Name: 2-Hydroxy-1,2,3-propanetricarboxylate-(Z)-2-[4-(1,2-diphyl-1-butenyl)phenoxy]-N,Ndimethyl ethanamine
Molecular Formula: C26H29NO•C6H8O7
CAS Number: 54965-24-1

Medically reviewed by Drugs.com. Last updated on Nov 4, 2019.

Warning

    Women with Ductal Carcinoma in Situ (DCIS) and Women at High Risk for Breast Cancer
  • Serious and life-threatening events associated with tamoxifen in the risk reduction setting include uterine malignancies, stroke, and pulmonary embolism.128 Incidence rates for these events have been estimated from the Breast Cancer Prevention Trial (BCPT; also known as the National Surgical Adjuvant Breast and Bowel Project [NSABP] P-1 trial) (median length of follow-up 6.9 years).128

    Uterine malignancies consist of both endometrial adenocarcinoma (incidence rate per 1000 women-years of 2.2 for tamoxifen versus 0.71 for placebo) and uterine sarcoma (incidence rate per 1000 women-years of 0.17 for tamoxifen versus 0.04 for placebo).128

    For stroke, the incidence rate per 1000 women-years was 1.43 for tamoxifen versus 1 for placebo.128

    For pulmonary embolism, the incidence rate per 1000 women-years was 0.75 for tamoxifen versus 0.25 for placebo.128

  • Discuss potential benefits versus potential risks of these serious, sometimes fatal, events with women at high risk of breast cancer and women with DCIS considering tamoxifen to reduce their risk of developing breast cancer.128

  • The benefits of tamoxifen outweigh its risks in women already diagnosed with breast cancer.128

Introduction

A nonsteroidal estrogen agonist-antagonist; an antineoplastic agent.128

Uses for Tamoxifen Citrate

Adjuvant Therapy of Breast Cancer

An adjuvant to surgery and radiation therapy for the treatment of breast cancer in women with negative or positive axillary lymph nodes.110 121 128 130 133 136 194 195 196 198 204 205 253 254 258 Also reduces the occurrence of contralateral breast cancer in these women.128 253 254 258

Metastatic Breast Cancer

Palliative treatment of metastatic breast cancer in women.128 An alternative to ovarian ablative therapy (oophorectomy or radiation) in premenopausal women.128 133 158 159 160 161 162 163 164 165 166 167 168 169 183 Patients with estrogen receptor-positive tumors are more likely to respond.128 158 163 166

Reduction in Risk of Invasive Breast Cancer in Patients with DCIS

Reduction of risk of invasive breast cancer in patients with DCIS following surgery and radiation therapy.128 Base decision regarding use on an individualized assessment of potential benefits and risks of therapy.128

Reduction in Incidence of Breast Cancer in Women at High Risk

Reduction in the incidence of breast cancer in women at high risk for developing the disease.128 250 293 Base decision regarding use on an individualized assessment of potential benefits and risks of preventive therapy.269 271 299 308

ASCO considers tamoxifen an option in premenopausal or postmenopausal women ≥35 years of age with either a 5-year projected risk for developing breast cancer of ≥1.67% (based on Gail risk model) or a history of lobular carcinoma in situ (LCIS).337

Data regarding effect on breast cancer incidence in women with inherited mutations (e.g., BRCA1, BRCA2) are insufficient to support recommendations regarding tamoxifen use.128

Breast Cancer in Men

Palliative treatment of metastatic breast cancer in men.104 128 229 231 233 236 237 238 252 378

Adjunct to surgery in the treatment of breast cancer in men with positive axillary lymph nodes; used alone or in conjunction with combination chemotherapy.226 227 228 230 231 236 237 251 378

The high frequency of hormone receptors in tumors of men230 237 251 252 may explain the high response rate of male breast carcinoma to endocrine therapy.228 Treatment to date has been similar to that for women with breast cancer;226 229 231 233 238 however, experience in men is very limited.226 228 229 231 251

Pharmacogenomic Considerations for Tamoxifen Therapy of Breast Cancer

Variations in genes responsible for tamoxifen metabolism may affect treatment decision (e.g., alternative drug or dosage requirement).339 384

Exposure to endoxifen (major active metabolite of tamoxifen) is strongly associated with CYP2D6 metabolizer phenotype,339 349 354 355 359 360 383 and low endoxifen concentrations are associated with increased risk for disease recurrence in women receiving adjuvant tamoxifen therapy for breast cancer;339 355 359 however, the validity of CYP2D6 metabolizer phenotype as a predictor of the outcome of tamoxifen therapy is controversial.339 348 351 353 360 384

Although some experts do not recommend use of CYP2D6 genotyping to guide treatment decisions in patients with hormone receptor-positive breast cancer based on available evidence,338 the Clinical Pharmacogenetics Implementation Consortium (CPIC) and other experts recommend that women with CYP2D6 poor-, intermediate-, or normal/intermediate-metabolizer phenotypes (activity scores of 0–1) receive adjuvant endocrine therapy with an alternative agent (e.g., aromatase inhibitor in postmenopausal women; aromatase inhibitor plus ovarian suppression in premenopausal women).339 384 If an aromatase inhibitor is contraindicated, CPIC and these experts state that an increased tamoxifen dosage of 40 mg daily may be considered, but endoxifen concentrations may still be suboptimal in those with a CYP2D6 poor-metabolizer phenotype.339 354 384

Albright Syndrome

Has been used to reduce the frequency of vaginal bleeding episodes and to reduce the rate of increase in bone age in girls with Albright syndrome (also known as McCune-Albright syndrome) and precocious puberty.128

Long-term effects beyond one year not established.128 (See Pediatric Use under Cautions.)

Tamoxifen Citrate Dosage and Administration

General

  • Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.

Administration

Oral Administration

Administer orally as a single daily dose or in divided doses; administer dosages >20 mg daily in divided doses (morning and evening).128

Dosage

Available as tamoxifen citrate; dosage expressed in terms of tamoxifen.128

Adults

Breast Cancer
Adjuvant Therapy
Oral

20–40 mg daily.100 102 110 121 128 129 130 194 195 196 205 In several clinical studies, no evidence indicating that dosages >20 mg daily are necessary.112 128

Patients with CYP2D6 poor-, intermediate-, or normal/intermediate-metabolizer phenotypes (activity scores of 0–1): Some experts state that 40 mg daily may be considered.339 354 384 (See Pharmacogenomic Considerations for Tamoxifen Therapy of Breast Cancer under Uses.)

Optimum duration of adjuvant therapy generally is 5 years;128 194 195 196 253 254 256 257 291 328 however, continuation of adjuvant therapy for an additional 5 years (for a total of 10 years) may be considered based on menopausal status.332 338 Magnitude of benefit of extended tamoxifen therapy (i.e., >5 years) expected to be lower in women with small tumors and/or node-negative disease.332

Metastatic Breast Cancer
Oral

20–40 mg daily.128 a Usual initial dosage is 20 mg daily.a

Ductal Carcinoma in Situ
Oral

20 mg daily for 5 years.128

Reduction in the Incidence of Breast Cancer in Women at High Risk
Oral

20 mg daily for 5 years.128 270 284 291

Breast Cancer in Men
Oral

Metastatic breast cancer: 20–40 mg daily.a

Adjunct to surgery: 20 mg daily has been used.227 231 Optimum duration of therapy not established; however, some clinicians suggest a similar duration in men as in women (i.e., 5–10 years).227 378 Individualize decisions about duration of therapy (as in women) based on risk of disease recurrence and adverse effects.378

Prescribing Limits

Adults

Breast Cancer
Adjuvant Therapy
Oral

In several studies, no evidence that dosages >20 mg daily are more effective.112 128

Safety of dosages >40 mg daily in patients with CYP2D6 poor-metabolizer phenotype not established,354 even though concentrations of endoxifen (major active metabolite) may remain suboptimal.339 354 384

Cautions for Tamoxifen Citrate

Contraindications

  • Known hypersensitivity to tamoxifen or any ingredient in the formulation.128

  • When used in women with DCIS and women at high risk for breast cancer, history of DVT or pulmonary embolism.128 278 293

  • When used in women with DCIS and women at high risk for breast cancer, concurrent anticoagulant therapy with a warfarin derivative.128 309

Warnings/Precautions

Warnings

Effects on the Uterus

Increased incidence of uterine malignancies, sometimes fatal, reported.128 330 Most uterine malignancies have been classified as adenocarcinoma of the endometrium; rare uterine sarcomas also reported.128 330 (See Boxed Warning.) Uterine sarcoma generally associated with more advanced disease at the time of diagnosis, poorer prognosis, and shorter survival.128 330 Promptly evaluate gynecologic symptoms (i.e., menstrual irregularities, abnormal vaginal bleeding, changes in vaginal discharge, pelvic pain or pressure).128 163 183 330

Endometrial changes, including hyperplasias and polyps, endometriosis, and uterine fibroids reported.128 180 258 259 274 Ovarian cysts reported in a small number of premenopausal women with advanced breast cancer.128

Menstrual irregularities and amenorrhea also reported.128

Thromboembolic Effects

Increased incidence of thromboembolic events, including DVT128 293 and pulmonary embolism;128 269 270 293 stroke128 293 also reported.128 269 277 293 Some cases of stroke and pulmonary emboli have been fatal.128 (See Boxed Warning.) Concomitant use with chemotherapy may increase incidence of these events.128

Screening patients for factor V Leiden and prothrombin G20210A mutations does not appear to aid in identifying those who should not receive tamoxifen.128

Other Warnings and Precautions

Hypercalcemia

Hypercalcemia reported in patients with metastatic breast cancer who have bone metastases.128 129 If hypercalcemia occurs, take appropriate measures; if severe, discontinue tamoxifen.128 129

Hepatic Effects

Liver cancer reported.128

Changes in AST, ALT, bilirubin and/or alkaline phosphatase concentrations reported; severe hepatic abnormalities including fatty changes in the liver, cholestasis, hepatitis, and hepatic necrosis (some fatal) reported rarely.128

Manufacturer recommends periodic monitoring of liver function tests.128

Ocular Effects

Visual disturbances, decrement in color vision perception, corneal changes, cataracts, optic neuritis, retinal vein thrombosis, intraretinal crystals, posterior subcapsular opacities, and/or retinopathy reported.128 190 191 192 193 258 268 326

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.128 If inadvertently used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard, including possible long-term risk of a diethylstilbestrol-like syndrome.128 (See Advice to Patients.)

When used to reduce the incidence of breast cancer in sexually active women, initiate therapy during menstruation.128 In women with menstrual irregularity, a negative β-human chorionic gonadotropin test immediately prior to therapy is sufficient.128

Hematologic Effects

Thrombocytopenia, neutropenia, pancytopenia, and leukopenia reported; caution in patients with leukopenia or thrombocytopenia.128 Periodic CBCs, including platelet count, recommended.128

Hyperlipidemia

Lipoprotein abnormalities (e.g., hypertriglyceridemia,324 325 marked hyperlipoproteinemia185 186 187 ) reported infrequently.128 185 186 187 188 Periodic monitoring of serum triglycerides and cholesterol recommended in patients with preexisting hyperlipidemia.128 324

Specific Populations

Pregnancy

Category D.128 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether tamoxifen is distributed into milk.128 Discontinue nursing or the drug because of potential risk to nursing infant.128 May decrease early postpartum milk production.128

Pediatric Use

Safety and efficacy in girls 2–10 years of age with Albright syndrome and precocious puberty not studied beyond 1 year.128 Increased uterine volume reported but long-term effects not established; continued monitoring recommended.128 (See Special Populations under Pharmacokinetics.)

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.128

Common Adverse Effects

Hot flashes, vaginal discharge, menstrual irregularities, weight loss.128

Interactions for Tamoxifen Citrate

Metabolized by multiple CYP isoenzymes (e.g., 1A2, 2B6, 2C9, 2C19, 2D6, 3A4/5), but principal pathway involves demethylation by CYP3A4/5, then hydroxylation by CYP2D6, to form major active metabolite (endoxifen).339 347 380

Tamoxifen and its metabolites also metabolized by multiple uridine diphosphate-glucuronosyltransferase (UGT) isoenzymes and to a lesser extent by sulfotransferases (mainly SULT1A1).339 348 380 381

Drugs Affecting Hepatic Microsomal Enzymes

CYP2D6 inhibitors: Possible decreased plasma concentrations of endoxifen;339 351 384 385 data regarding effects on tamoxifen efficacy are inconclusive.348 385 Some experts make recommendations regarding concomitant use based on CYP2D6 genotyping (see Table 1).339 Other experts (whose recommendations do not depend on genotype testing) state that it is reasonable to avoid concomitant use of CYP2D6 inhibitors, particularly moderate or potent inhibitors, when possible in patients receiving tamoxifen.334 338 384 385

CPIC Recommendations Regarding Concomitant Use of Tamoxifen and CYP2D6 Inhibitors339

CYP2D6 Metabolizer Phenotype

Recommendation

Poor

Alternative adjuvant endocrine therapy (rather than tamoxifen) recommended

Intermediate

Avoid concomitant use of weak, moderate, or potent CYP2D6 inhibitors

Normal/intermediate

Avoid concomitant use of weak, moderate, or potent CYP2D6 inhibitors

Normal

Avoid concomitant use of moderate or potent CYP2D6 inhibitors

Ultrarapid

Avoid concomitant use of moderate or potent CYP2D6 inhibitors

CYP inducers: Possible decreased plasma concentrations of tamoxifen and endoxifen.128 385 Clinical importance not established.385 Nonetheless, some clinicians suggest avoiding concomitant use of agents that induce multiple isoenzymes and transporters.385

Drugs Metabolized by Hepatic Microsomal Enzymes

Effect of tamoxifen on drugs that require mixed function oxidases for activation unknown.128

Cytotoxic Agents

Increased risk of thromboembolic events.128

Specific Drugs

Drug

Interaction

Comments

Aminoglutethimide (no longer commercially available in US)

Decreased exposure to tamoxifen, endoxifen, and other metabolites; endoxifen concentrations undetectable in some patients128 385 386

Clinical importance unknown385

Some clinicians suggest avoiding concomitant use385

Anticoagulants (e.g., warfarin)

Enhanced warfarin effects128 170 171 172

Careful monitoring of PT is recommended128 170 171 172

When used in women with DCIS or at high risk for breast cancer, concomitant use contraindicated128

Anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin)

CYP inducers: Possible decreased plasma concentrations of tamoxifen and endoxifen128 385

Phenobarbital: Decreased serum tamoxifen concentrations reported128

Phenytoin: Low endoxifen concentrations reported385 387

Clinical importance not established385

Inducers of multiple CYP enzymes/transporters: Some clinicians suggest avoiding concomitant use385

Antimycobacterial agents (rifabutin, rifampin, rifapentine)

Possible decreased plasma concentrations of tamoxifen and endoxifen128 385

Rifampin: Decreased tamoxifen and endoxifen exposure128 385

Clinical importance unknown385

Some clinicians suggest avoiding concomitant use385

Aromatase inhibitors (e.g., anastrozole, exemestane, letrozole)

Anastrozole: Decreased plasma anastrozole concentrations,128 but estradiol suppression similar with or without concomitant tamoxifen;345 efficacy of the combination regimen as adjuvant therapy not superior to that of tamoxifen alone128 345

Letrozole: Decreased plasma letrozole concentrations128

Clinical importance of pharmacokinetic interaction unknown345

Concomitant use not recommended128 343 344

Bromocriptine

Increased plasma tamoxifen and N-desmethyltamoxifen concentrations128

Bupropion

Potent CYP2D6 inhibition may decrease plasma endoxifen concentrations 339 351 384 385

Clinical importance unknown348 385

Some experts recommend avoiding concomitant use334 338 339 384 385

Cyclosporine

Competitively inhibited formation of N-desmethyltamoxifen in vitro128

Clinical importance unknown128

Diltiazem

Competitively inhibited formation of N-desmethyltamoxifen in vitro128

Clinical importance unknown128

Erythromycin

Competitively inhibited formation of N-desmethyltamoxifen in vitro128

Clinical importance unknown128

Medroxyprogesterone

Decreased plasma N-desmethyltamoxifen concentrations but did not reduce plasma tamoxifen concentrations128

Nifedipine

Competitively inhibited formation of N-desmethyltamoxifen in vitro128

Clinical importance unknown128

Quinidine

Potent CYP2D6 inhibition may decrease plasma endoxifen concentrations 339 351 384 385

Clinical importance unknown348 385

Some experts recommend avoiding concomitant use334 338 339 384 385

SSRIs (e.g., fluoxetine, paroxetine)

Potent CYP2D6 inhibitors: Decreased plasma concentrations of endoxifen348 351 384 385

Clinical importance unknown334 348 385

Moderate or potent CYP2D6 inhibitors: Some experts recommend avoiding concomitant use; if an antidepressant is required, use an SSRI or SNRI with little or no CYP2D6 inhibitory potential (e.g., citalopram, escitalopram, venlafaxine, desvenlafaxine)334 338 339 384 385

St. John's wort (Hypericum perforatum)

Possible decreased plasma concentrations of tamoxifen and endoxifen385

Clinical importance unknown385

Some clinicians suggest avoiding concomitant use385

Tamoxifen Citrate Pharmacokinetics

Absorption

Bioavailability

Absorbed slowly following oral administration; peak serum concentrations of tamoxifen occur about 3–6 hours after a single dose.128 137 138 139 140 141

Animal studies suggest tamoxifen and/or its metabolites undergo extensive enterohepatic circulation.142

Plasma Concentrations

Steady-state concentrations of tamoxifen are attained after 3–4 weeks and those of N-desmethyltamoxifen, an active metabolite, are attained after 3–8 weeks.128 137 140 143 145

Distribution

Extent

Not fully characterized.128

Not known whether tamoxifen is distributed into milk.128

Elimination

Metabolism

Rapidly and extensively metabolized in the liver,26 28 140 142 143 144 145 146 148 149 150 151 380 principally by demethylation and hydroxylation.140 143 144 145 146 148 149 150 151 339 380 381

Multiple CYP isoenzymes (e.g., 1A2, 2B6, 2C9, 2C19, 2D6, 3A4/5) contribute to metabolism, but the principal pathway involves demethylation of the parent drug, mediated mainly by CYP3A4/5, to form N-desmethyltamoxifen, followed by CYP2D6-mediated hydroxylation to form 4-hydroxy-N-desmethyltamoxifen (also known as endoxifen).339 347 380 Formation of N-desmethyltamoxifen accounts for approximately 92% of the metabolism of the parent drug.347 381

Tamoxifen also is metabolized to a lesser extent (approximately 7%) by CYP isoenzymes, mainly CYP2D6, to form 4-hydroxytamoxifen, which is further metabolized to form endoxifen and polar conjugates.339 347 380 381 Several other metabolites also identified.149 150 151 152 347 380 382

Tamoxifen and its metabolites also are metabolized by multiple UGT isoenzymes and to a lesser extent by sulfotransferases (mainly SULT1A1) to form glucuronide and sulfate conjugates, respectively.339 348 380 381

N-Desmethyltamoxifen has biologic activity similar to that of the parent drug.128 379 Endoxifen and 4-hydroxytamoxifen exhibit 100-fold greater affinity for estrogen receptors and 30- to 100-fold greater suppression of estrogen-dependent cell proliferation compared with tamoxifen; because plasma concentrations of endoxifen are up to tenfold higher than those of 4-hydroxytamoxifen, endoxifen is considered the major active metabolite.339 348 349 350 379 381 383 384

Elimination Route

Excreted principally in feces as polar conjugates.128

Half-life

Tamoxifen: 5–7 days.28 137 139 145

N-Desmethyltamoxifen: 9–14 days.128 139 145

Special Populations

Clearance higher in girls 2–10 years of age than in women; exposure to N-desmethyltamoxifen in these pediatric patients similar to adults.128

CYP2D6 metabolizer phenotype: Endoxifen exposure is strongly associated with CYP2D6 metabolizer phenotype, but genetic polymorphism of CYP2D6 explains only about 30–53% of the observed variability in endoxifen concentrations.339 349 354 355 359 360 383 Individuals with low CYP2D6 activity have lower serum endoxifen concentrations, but studies evaluating association with breast cancer recurrence have been inconclusive.334 339 348 355 (See Pharmacogenomic Considerations for Tamoxifen Therapy of Breast Cancer under Uses.)

Effects of age, gender, race, and hepatic impairment on tamoxifen pharmacokinetics not established.128

Stability

Storage

Oral

Tablets

Well-closed, light-resistant containers at 20–25°C.128

Actions

  • Acts as an estrogen antagonist on breast tissue and in the CNS and as an estrogen agonist on endometrium, bone, and lipids.311

  • In breast epithelial tissue, increases production of inhibitory factors and decreases production of stimulatory factors that influence breast cell growth.271 286 287 323

  • Reduces bone resorption and bone turnover.265 266 267 316

  • Decreases total and LDL-cholesterol concentrations.318 319 320 Less favorably, decreases HDL-cholesterol concentrations and increases triglyceride concentrations.318 319 320

  • Acts as an estrogen agonist on the uterus and exhibits proliferative and tumor-promoting effects on the endometrium.311

Advice to Patients

  • Importance of receiving routine gynecologic care and of immediately informing clinician if any new breast lumps or abnormal gynecologic symptoms, including abnormal vaginal bleeding, change in vaginal discharge, menstrual irregularities, or pelvic pain/pressure, occur.128 163 183

  • Importance of informing clinician of any changes in vision.128 190 191 192 193 258 268

  • Importance of immediately informing clinician of unexplained shortness of breath or leg swelling/tenderness.128

  • Importance of periodic monitoring, including liver function test monitoring and blood counts.128

  • Advise patients at high risk of breast cancer that tamoxifen may decrease the incidence of breast cancer, but may not eliminate the risk of the disease.128

  • Advise patients with DCIS that tamoxifen may decrease the incidence of invasive breast cancer, but has not been shown to affect survival.128

  • Importance of women informing clinicians immediately if they are or plan to become pregnant; importance of avoiding pregnancy during therapy;119 128 243 importance of using effective nonhormonal contraception while receiving tamoxifen and for 2 months after discontinuing the drug.128 Necessity of advising pregnant patients of the risk to the fetus.128

  • Importance of reading the medication guide; the guide is for women using tamoxifen to lower their risk of breast cancer or with DCIS.128

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements.128 385

  • Importance of women informing clinicians if they plan to breast-feed.128

  • Importance of informing patients of other important precautionary information.128 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Tamoxifen Citrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

10 mg (of tamoxifen)*

Tamoxifen Citrate Tablets

20 mg (of tamoxifen)*

Tamoxifen Citrate Tablets

Tablets, film-coated

10 mg (of tamoxifen)*

Tamoxifen Citrate Tablets

20 mg (of tamoxifen)*

Tamoxifen Citrate Tablets

AHFS DI Essentials™. © Copyright 2020, Selected Revisions November 4, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

26. Fromson JM, Sharp DS. The selective uptake of tamoxifen by human uterine tissue. J Obstet Gynaecol Br Comm. 1974; 81:321-3.

28. Fromson JM, Pearson S. The metabolism of tamoxifen (I.C.I. 46,474). Part II: in female patients. Xenobiotica. 1973; 3:711-4. http://www.ncbi.nlm.nih.gov/pubmed/4783632?dopt=AbstractPlus

100. Nolvadex Adjuvant Trial Organisation. Controlled trial of tamoxifen as adjuvant agent in management of early breast cancer: interim analysis at four years. Lancet. 1983; 1:257-61. http://www.ncbi.nlm.nih.gov/pubmed/6130291?dopt=AbstractPlus

101. Nolvadex Adjuvant Trial Organisation. Improved survival amongst patients treated with adjuvant tamoxifen after mastectomy for early breast cancer. Lancet. 1983; 2:450.

102. Ribeiro G, Palmer MK. Adjuvant tamoxifen for operable carcinoma of the breast: report of clinical trial by the Christie Hospital and Holt Radium Institute. BMJ. 1983; 286:827-30. http://www.ncbi.nlm.nih.gov/pubmed/6403101?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1547148&blobtype=pdf

103. Brinkley D. Adjuvant questions. BMJ. 1984; 288:1709-10. http://www.ncbi.nlm.nih.gov/pubmed/6428507?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1441548&blobtype=pdf

104. Patterson JS, Battersby LA, Bach BK. Use of tamoxifen in advanced male breast cancer. Cancer Treat Rep. 1980; 64:801-4. http://www.ncbi.nlm.nih.gov/pubmed/7427964?dopt=AbstractPlus

105. Becher R, Höffken K, Pape H et al. Tamoxifen treatment before orchiectomy in advanced breast cancer in men. N Engl J Med. 1981; 305:169-70. http://www.ncbi.nlm.nih.gov/pubmed/7242589?dopt=AbstractPlus

106. Hortobagyi GN, Distefano A, Legha SS et al. Hormonal therapy with tamoxifen in male breast cancer. Cancer Treat Rep. 1979; 63:539-41. http://www.ncbi.nlm.nih.gov/pubmed/221118?dopt=AbstractPlus

107. Stathopoulos GP, Karvountzis GG, Yiotis J. Tamoxifen in carcinoid syndrome. N Engl J Med. 1981; 305:52. http://www.ncbi.nlm.nih.gov/pubmed/7231519?dopt=AbstractPlus

108. Myers CF, Ershler WB, Tannenbaum MA et al. Tamoxifen and carcinoid tumor. Ann Intern Med. 1982; 96:383. http://www.ncbi.nlm.nih.gov/pubmed/7059114?dopt=AbstractPlus

109. Moertel CG, Engstrom PF, Schutt AJ. Tamoxifen therapy for metastatic carcinoid tumor: a negative study. Ann Intern Med. 1984; 100:531-2. http://www.ncbi.nlm.nih.gov/pubmed/6200021?dopt=AbstractPlus

110. Nolvadex Adjuvant Trial Organisation. Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer: analysis at six years. Lancet. 1985; 1:836-40. http://www.ncbi.nlm.nih.gov/pubmed/2858709?dopt=AbstractPlus

111. Rose C, Thorpe SM, Andersen KW et al. Beneficial effect of adjuvant tamoxifen therapy in primary breast cancer patients with high oestrogen receptor values. Lancet. 1985; 1:16-9. http://www.ncbi.nlm.nih.gov/pubmed/2856949?dopt=AbstractPlus

112. National Institutes of Health Office of Medical Applications of Research. Consensus conference: adjuvant chemotherapy for breast cancer. JAMA. 1985; 254:3461-3. http://www.ncbi.nlm.nih.gov/pubmed/4068189?dopt=AbstractPlus

113. Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984; 1:1256-60. http://www.ncbi.nlm.nih.gov/pubmed/6144974?dopt=AbstractPlus

114. Fisher B, Fisher ER, Redmond C. A brief overview of findings from NSABP trials of adjuvant therapy. Recent Results Cancer Res. 1984; 96:55-65. http://www.ncbi.nlm.nih.gov/pubmed/6101262?dopt=AbstractPlus

115. Hubay CA, Gordon NH, Crowe JP et al. Antiestrogen-cytotoxic chemotherapy and Bacillus Calmette-Guerin vaccination in stage II breast cancer: seventy-two-month follow-up. Surgery. 1984; 96:61-72. http://www.ncbi.nlm.nih.gov/pubmed/6740497?dopt=AbstractPlus

116. Cummings FJ, Gray R, Davis TE et al. Adjuvant tamoxifen treatment of elderly women with Stage II breast cancer: a double-blind comparison with placebo. Ann Intern Med. 1985; 103:324-9. http://www.ncbi.nlm.nih.gov/pubmed/3896085?dopt=AbstractPlus

117. Gau T (Stuart Pharmaceuticals, Wilmington, DE): Personal communication; 1986 Jan 13.

118. Kaiser-Kupfer MI, Lippman ME. Tamoxifen retinopathy. Cancer Treat Rep. 1978; 62:315-20. http://www.ncbi.nlm.nih.gov/pubmed/647693?dopt=AbstractPlus

119. Diver JMJ, Jackson IM, Fitzgerald JD. Tamoxifen and non-malignant indications. Lancet. 1986; 1:733. http://www.ncbi.nlm.nih.gov/pubmed/2870236?dopt=AbstractPlus

120. Kaiser-Kupfer MI, Kupfer C, Rodrigues MM. Tamoxifen retinopathy: a clinicopathologic report. Ophthalmology. 1981; 88:89-93. http://www.ncbi.nlm.nih.gov/pubmed/7243233?dopt=AbstractPlus

121. Report from the Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC), Edinburgh. Adjuvant tamoxifen in the management of operable breast cancer: the Scottish trial. Lancet. 1987; 2:171-5. http://www.ncbi.nlm.nih.gov/pubmed/2885637?dopt=AbstractPlus

122. Fisher B, Brown A, Wolmark N et al. Prolonging tamoxifen therapy for primary breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project Clinical Trial. Ann Intern Med. 1987; 106:649-54. http://www.ncbi.nlm.nih.gov/pubmed/3551710?dopt=AbstractPlus

123. Tormey DC. Long-term adjuvant therapy with tamoxifen in breast cancer: how long is long? Ann Intern Med. 1987; 106:762-4. Editorial.

124. Zielinski CC, Kubista E, Salzer H et al. Adjuvant chemotherapy combined with tamoxifen in postmenopausal patients with stage II breast cancer. Lancet. 1986; 2:1164. http://www.ncbi.nlm.nih.gov/pubmed/2877314?dopt=AbstractPlus

125. Fentiman IS, Caleffi M, Brame E et al. Double-blind controlled trial of tamoxifen therapy for mastalgia. Lancet. 1986; 1:287-8. http://www.ncbi.nlm.nih.gov/pubmed/2868162?dopt=AbstractPlus

126. Fentiman IS. Tamoxifen and mastalgia: an emerging indication. Drugs. 1986; 32:477-80. http://www.ncbi.nlm.nih.gov/pubmed/3539572?dopt=AbstractPlus

127. Fisher B, Redmond C, Brown A et al. Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer. J Clin Oncol. 1983; 1:227-41. http://www.ncbi.nlm.nih.gov/pubmed/6366135?dopt=AbstractPlus

128. Mayne Pharma. Tamoxifen citrate tablets prescribing information. Greenville, NC; 2016 Jul.

129. Legha SS. Tamoxifen in the treatment of breast cancer. Ann Intern Med. 1988; 109:219-28. http://www.ncbi.nlm.nih.gov/pubmed/3291659?dopt=AbstractPlus

130. National Cancer Institute. Clinical alert on breast cancer. Bethesda, MD: National Cancer Institute; 1988 May 18.

131. Bradbeer JW, Kyngdon J. Primary treatment of breast cancer in elderly women with tamoxifen. Clin Oncol. 1983; 9:31-4. http://www.ncbi.nlm.nih.gov/pubmed/6851305?dopt=AbstractPlus

132. Taylor SG IV, Gelman RS, Falkson G et al. Combination chemotherapy compared to tamoxifen as initial therapy for stage IV breast cancer in elderly women. Ann Intern Med. 1986; 104:455-61. http://www.ncbi.nlm.nih.gov/pubmed/3513684?dopt=AbstractPlus

133. Glick JH. Meeting highlights: adjuvant therapy for breast cancer. J Natl Cancer Inst. 1988; 80:471-5. http://www.ncbi.nlm.nih.gov/pubmed/3367387?dopt=AbstractPlus

134. Delozier T, Julien JP, Juret P et al. Adjuvant tamoxifen in postmenopausal breast cancer: preliminary results of a randomized trial. Breast Cancer Res Treat. 1986; 7:105-10. http://www.ncbi.nlm.nih.gov/pubmed/3521767?dopt=AbstractPlus

135. Fisher B, Redmond C, Brown A et al. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial. J Clin Oncol. 1986; 4:459-71. http://www.ncbi.nlm.nih.gov/pubmed/2856857?dopt=AbstractPlus

136. Early Breast Cancer Trialists’ Collaborative Group. Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer: an overview of 61 randomized trials among 28,896 women. N Engl J Med. 1988; 319:1681-92. http://www.ncbi.nlm.nih.gov/pubmed/3205265?dopt=AbstractPlus

137. Fabian C, Sternson L, Barnett M. Clinical pharmacology of tamoxifen in patients with breast cancer: comparison of traditional and loading dose schedules. Cancer Treat Rep. 1980; 64:765-73. http://www.ncbi.nlm.nih.gov/pubmed/7427961?dopt=AbstractPlus

138. Adam HK, Gay MA, Moore RH. Measurement of tamoxifen in serum by thin-layer densitometry. J Endocrinol. 1980; 84:35-42. http://www.ncbi.nlm.nih.gov/pubmed/7359080?dopt=AbstractPlus

139. Adam HK, Patterson JS, Kemp JV. Studies on the metabolism and pharmacokinetics of tamoxifen in normal volunteers. Cancer Treat Rep. 1980; 64:761-4. http://www.ncbi.nlm.nih.gov/pubmed/7427960?dopt=AbstractPlus

140. McVie JG, Simonetti GPC, Stevenson D et al. The bioavailability of Tamoplex(tamoxifen). Part 1: a pilot study. Methods Find Exp Clin Pharmacol. 1986; 8:505-12. http://www.ncbi.nlm.nih.gov/pubmed/3747644?dopt=AbstractPlus

141. Wilkinson P, Ribeiro G, Adam H et al. Clinical pharmacology of tamoxifen and N-desmethyltamoxifen in patients with advanced breast cancer. Cancer Chemother Pharmacol. 1980; 5:109-11. http://www.ncbi.nlm.nih.gov/pubmed/7471314?dopt=AbstractPlus

142. Fromson JM, Pearson S, Bramah S. The metabolism of tamoxifen (I.C.I. 46,474). Part I: in laboratory animals. Xenobiotica. 1973; 3:693-709. http://www.ncbi.nlm.nih.gov/pubmed/4361333?dopt=AbstractPlus

143. Milano G, Etienne MC, Frenay M et al. Optimised analysis of tamoxifen and its main metabolites in the plasma and cytosol of mammary tumours. Br J Cancer. 1987; 55:509-12. http://www.ncbi.nlm.nih.gov/pubmed/3606944?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2001713&blobtype=pdf

144. Daniel P, Gaskell SJ, Bishop H et al. Determination of tamoxifen and biologically active metabolites in human breast tumours and plasma. Eur J Cancer Clin Oncol. 1981; 17:1183-9. http://www.ncbi.nlm.nih.gov/pubmed/7199465?dopt=AbstractPlus

145. Jordan VC. Metabolites of tamoxifen in animals and man: identification, pharmacology, and significance. Breast Cancer Res Treat. 1982; 2:123-38. http://www.ncbi.nlm.nih.gov/pubmed/6184101?dopt=AbstractPlus

146. Soininen K, Kleimola T, Elomaa I et al. The steady-state pharmacokinetics of tamoxifen and its metabolites in breast cancer patients. J Int Med Res. 1986; 14:162-5. http://www.ncbi.nlm.nih.gov/pubmed/3522312?dopt=AbstractPlus

147. Ribeiro GG, Wilkinson PM. A clinical assessment of loading dose tamoxifen for advanced breast carcinoma. Clin Oncol. 1984; 10:363-7. http://www.ncbi.nlm.nih.gov/pubmed/6509818?dopt=AbstractPlus

148. Adam HK, Douglas EJ, Kemp JV. The metabolism of tamoxifen in humans. Biochem Pharmacol. 1979; 27:145-7.

149. Bain RR, Jordan VC. Identification of a new metabolite of tamoxifen in patient serum during breast cancer therapy. Biochem Pharmacol. 1983; 32:373-5. http://www.ncbi.nlm.nih.gov/pubmed/6870963?dopt=AbstractPlus

150. Jordan VC, Bain RR, Brown RR et al. Determination and pharmacology of a new hydroxylated metabolite of tamoxifen observed in patient sera during therapy for advanced breast cancer. Cancer Res. 1983; 43:1446-50. http://www.ncbi.nlm.nih.gov/pubmed/6825112?dopt=AbstractPlus

151. Murphy C, Fotsis T, Pantzar P et al. Analysis of tamoxifen and its metabolites in human plasma by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM). J Steroid Biochem. 1987; 26:547-55. http://www.ncbi.nlm.nih.gov/pubmed/3586671?dopt=AbstractPlus

152. Kemp JV, Adam HK, Wakeling AE et al. Identification and biological activity of tamoxifen and metabolites in human serum. Biochem Pharmacol. 1983; 32:2045-52. http://www.ncbi.nlm.nih.gov/pubmed/6870933?dopt=AbstractPlus

153. Jordan VC, Collins MM, Rowsby L et al. A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J Endocrinol. 1977; 75:305-16. http://www.ncbi.nlm.nih.gov/pubmed/591813?dopt=AbstractPlus

154. Wakeling AE, Slater SR. Estrogen-receptor binding and biologic activity of tamoxifen and its metabolites. Cancer Treat Rep. 1980; 64:741-4. http://www.ncbi.nlm.nih.gov/pubmed/7427959?dopt=AbstractPlus

155. Fabian C, Tilzer L, Sternson L. Comparative binding affinities of tamoxifen, 4-hydroxytamoxifen, and desmethyltamoxifen for estrogen receptors isolated from human breast carcinoma: correlation with blood levels in patients with metastatic breast cancer. Biopharm Drug Dispos. 1981; 2:381-90. http://www.ncbi.nlm.nih.gov/pubmed/7317574?dopt=AbstractPlus

156. Borgna JL, Rochefort H. Hydroxylated metabolites of tamoxifen are formed in vivo and bound to estrogen receptor in target tissues. J Biol Chem. 1981; 256:859-68. http://www.ncbi.nlm.nih.gov/pubmed/7451477?dopt=AbstractPlus

157. Coezy E, Borgna JL, Rochefort H. Tamoxifen and metabolites in MCF, cells: correlation between binding to estrogen receptor and inhibition of cell growth. Cancer Res. 1982; 42:317-23. http://www.ncbi.nlm.nih.gov/pubmed/7053859?dopt=AbstractPlus

158. Pritchard KI, Thomson DB, Myers RE et al. Tamoxifen therapy in premenopausal patients with metastatic breast cancer. Cancer Treat Rep. 1980; 64:787-96. http://www.ncbi.nlm.nih.gov/pubmed/7427962?dopt=AbstractPlus

159. Manni A, Pearson OH. Antiestrogen-induced remissions in premenopausal women with stage IV breast cancer: effects on ovarian function. Cancer Treat Rep. 1980; 64:779-85. http://www.ncbi.nlm.nih.gov/pubmed/6775808?dopt=AbstractPlus

160. Sawka CA, Pritchard KI, Paterson AH et al. Role and mechanism of action of tamoxifen in premenopausal women with metastatic breast carcinoma. Cancer Res. 1986; 46:3152-6. http://www.ncbi.nlm.nih.gov/pubmed/3084082?dopt=AbstractPlus

161. Ingle JN, Krook JE, Green SJ et al. Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastatic breast cancer. J Clin Oncol. 1986; 4:178-85. http://www.ncbi.nlm.nih.gov/pubmed/3511184?dopt=AbstractPlus

162. Buchanan RB, Blamey RW, Durrant KR et al. A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer. J Clin Oncol. 1986; 4:1326-30. http://www.ncbi.nlm.nih.gov/pubmed/3528402?dopt=AbstractPlus

163. Legha SS. Tamoxifen in the treatment of breast cancer. Ann Intern Med. 1988; 109:219-28. http://www.ncbi.nlm.nih.gov/pubmed/3291659?dopt=AbstractPlus

164. Hoogstraten B, Fletcher WS, Gad-el-Mawla N et al. Tamoxifen and oophorectomy in the treatment of recurrent breast cancer. A Southwest Oncology Group study. Cancer Res. 1982; 42:4788-91. http://www.ncbi.nlm.nih.gov/pubmed/7127314?dopt=AbstractPlus

165. Yoshida M, Murai H, Miura S. Tamoxifen therapy for premenopausal and postmenopausal Japanese females with advanced breast cancer. Jpn J Clin Oncol. 1982; 12:57-63.

166. Margreiter R, Wiegele J. Tamoxifen (Nolvadex) for premenopausal patients with advanced breast cancer. Breast Cancer Res Treat. 1984; 4:45-8. http://www.ncbi.nlm.nih.gov/pubmed/6365211?dopt=AbstractPlus

167. Planting AS, Alexieva-Figusch J, Blonk-VdWijst J et al. Tamoxifen therapy in premenopausal women with metastatic breast cancer. Cancer Treat Res. 1985; 69:363-8.

168. Wada T, Koyama H, Terasawa T. Effect of tamoxifen in premenopausal Japanese women with advanced breast cancer. Cancer Treat Rep. 1981; 65:728-9. http://www.ncbi.nlm.nih.gov/pubmed/7248991?dopt=AbstractPlus

169. Hoogstraten B, Gad-el-Mawla N, Maloney TR et al. Combined modality therapy for first recurrence of breast cancer. A Southwest Oncology Group study. Cancer. 1984; 54:2248-56. http://www.ncbi.nlm.nih.gov/pubmed/6488144?dopt=AbstractPlus

170. Lodwick R, McConkey B, Brown AM. Life threatening interaction between tamoxifen and warfarin. BMJ. 1987; 295:1141. http://www.ncbi.nlm.nih.gov/pubmed/3120919?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1248224&blobtype=pdf

171. Tenni P, Lalich DL, Byrne MJ. Life threatening interaction between tamoxifen and warfarin. BMJ. 1989; 298:93. http://www.ncbi.nlm.nih.gov/pubmed/2493305?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1835395&blobtype=pdf

172. Ritchie LD, Grant SMT. Tamoxifen–Warfarin interaction: the Aberdeen hospitals drug file. BMJ. 1989; 298:1253.

173. Fornander T, Rutquist LE, Cedermark B et al. Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet. 1989; 1:117-20. http://www.ncbi.nlm.nih.gov/pubmed/2563046?dopt=AbstractPlus

174. Hardell L. Tamoxifen as risk factor for carcinoma of corpus uteri. Lancet. 1988; 2:563. http://www.ncbi.nlm.nih.gov/pubmed/2900934?dopt=AbstractPlus

175. Killackey MA, Hakes TB, Pierce VK. Endometrial adenocarcinoma in breast cancer patients receiving antiestrogens. Cancer Treat Rep. 1985; 69:237-8. http://www.ncbi.nlm.nih.gov/pubmed/3971394?dopt=AbstractPlus

176. Jordan VC. Tamoxifen and endometrial cancer. Lancet. 1989; 1:733-4. http://www.ncbi.nlm.nih.gov/pubmed/2564550?dopt=AbstractPlus

177. Gottardis MM, Robinson SP, Satyaswaroop PG et al. Contrasting actions of tamoxifen on endometrial and breast tumor growth in the athymic mouse. Cancer Res. 1988; 48:812-5. http://www.ncbi.nlm.nih.gov/pubmed/3338079?dopt=AbstractPlus

178. Neven P, De Muylder X, Van Belle Y et al. Tamoxifen and the uterus and endometrium. Lancet. 1989; 1:375. http://www.ncbi.nlm.nih.gov/pubmed/2563519?dopt=AbstractPlus

179. Stewart HJ, Knight GM. Tamoxifen and the uterus and endometrium. Lancet. 1989; 1:375-6. http://www.ncbi.nlm.nih.gov/pubmed/18446929?dopt=AbstractPlus

180. Cano A, Matallin P, Legua V et al. Tamoxifen and the uterus and endometrium. Lancet. 1989; 1:376. http://www.ncbi.nlm.nih.gov/pubmed/18446930?dopt=AbstractPlus

181. Boccardo F, Bruzzi P, Rubagotti A et al. Estrogen-like action of tamoxifen on vaginal epithelium in breast cancer patients. Oncology. 1981; 38:281-5. http://www.ncbi.nlm.nih.gov/pubmed/7266969?dopt=AbstractPlus

182. Boccardo F, Guarneri D, Rubagotti A et al. Endocrine effects of tamoxifen in postmenopausal breast cancer patients. Tumori. 1984; 70:61-8. http://www.ncbi.nlm.nih.gov/pubmed/6538707?dopt=AbstractPlus

183. Buckley MMT, Goa KL. Tamoxifen: a reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic use. Drugs. 1989; 37:451-90. http://www.ncbi.nlm.nih.gov/pubmed/2661195?dopt=AbstractPlus

184. Cuzick J, Baum M. Tamoxifen and contralateral breast cancer. Lancet. 1985; 2:282. http://www.ncbi.nlm.nih.gov/pubmed/2862460?dopt=AbstractPlus

185. Brun LD, Gagne C, Rousseau C et al. Severe lipemia induced by tamoxifen. Cancer. 1986; 57:2123-6. http://www.ncbi.nlm.nih.gov/pubmed/3697911?dopt=AbstractPlus

186. Noguchi M, Taniya T, Tajiri K et al. Fatal hyperlipaemia in a case of metastatic breast cancer treated by tamoxifen. Br J Surg. 1987; 74:586-7. http://www.ncbi.nlm.nih.gov/pubmed/3620865?dopt=AbstractPlus

187. Taniya T, Noguchi M, Tajiri K et al. [A case report of hyperlipemia with giant fatty liver during adjuvant endocrine therapy by tamoxifen]. Gan No Rinsho. 1987; 33:300-4. http://www.ncbi.nlm.nih.gov/pubmed/3108557?dopt=AbstractPlus

188. Rossner S, Wallgren A. Serum lipoproteins and proteins after breast cancer surgery and effects of tamoxifen. Atherosclerosis. 1984; 52:339-46. http://www.ncbi.nlm.nih.gov/pubmed/6497936?dopt=AbstractPlus

189. McKeown CA, Swartz M, Blom J et al. Tamoxifen retinopathy. Br J Ophthalmol. 1981; 65:177-9. http://www.ncbi.nlm.nih.gov/pubmed/7225310?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1039458&blobtype=pdf

190. Vinding T, Nielsen NV. Retinopathy caused by treatment with tamoxifen in low dosage. Acta Ophthalmol. 1983; 61:45-50.

191. Griffiths MF. Tamoxifen retinopathy at low dosage. Am J Ophthalmol. 1987; 104:185-6. http://www.ncbi.nlm.nih.gov/pubmed/3039846?dopt=AbstractPlus

192. Ashford AR, Donev I, Tiwari RP et al. Reversible ocular toxicity related to tamoxifen therapy. Cancer. 1988; 61:33-5. http://www.ncbi.nlm.nih.gov/pubmed/3334951?dopt=AbstractPlus

193. Pugesgaard T, Von Eyben FE. Bilateral optic neuritis evolved during tamoxifen treatment. Cancer. 1986; 58:383-6. http://www.ncbi.nlm.nih.gov/pubmed/3719532?dopt=AbstractPlus

194. National Institutes of Health Office of Medical Applications of Research. Consensus conference: treatment of early-stage breast cancer. JAMA. 1991; 265:391-5. http://www.ncbi.nlm.nih.gov/pubmed/1984541?dopt=AbstractPlus

195. Fisher B, Redmond C, Wickerham L et al. Systemic therapy in patients with node-negative breast cancer: a commentary based on two national surgical adjuvant breast and bowel project (NSABP) clinical trials. Ann Intern Med. 1989; 111:703-12. http://www.ncbi.nlm.nih.gov/pubmed/2679288?dopt=AbstractPlus

196. Fisher B, Costantino J, Redmond C et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med. 1989; 320:479-84. http://www.ncbi.nlm.nih.gov/pubmed/2644532?dopt=AbstractPlus

197. Rosner D, Lane WW. One-third of node-negative breast cancer patients are highly curable by surgery alone, without need for adjuvant systemic therapy. Proc Annu Meet Am Soc Clin Oncol. 1990; 9:A63.

198. Redmond CK, Fisher B, Costantino J et al. Treatment of stage I breast cancer: the NSABP experience. Horm Res. 1989; 32(Suppl 1):175-80. http://www.ncbi.nlm.nih.gov/pubmed/2613203?dopt=AbstractPlus

199. Hillner BE, Smith TJ. Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer. N Engl J Med. 1991; 324:160-8. http://www.ncbi.nlm.nih.gov/pubmed/1898533?dopt=AbstractPlus

200. Anon. Adjuvant tamoxifen in early breast cancer. Lancet. 1987; 2:191-2. http://www.ncbi.nlm.nih.gov/pubmed/2885643?dopt=AbstractPlus

201. McGuire WL. Adjuvant therapy of node-negative breast cancer. N Engl J Med. 1989; 320:525-7. http://www.ncbi.nlm.nih.gov/pubmed/2915655?dopt=AbstractPlus

202. DeVita VT Jr. Breast cancer therapy: exercising all our options. N Engl J Med. 1989; 320:527-9. http://www.ncbi.nlm.nih.gov/pubmed/2915656?dopt=AbstractPlus

203. Wolmark N. 1989: The year of adjuvant therapy in node-negative breast cancer. Cancer: Princ Pract Oncol Updates. 1989; 3:1-10.

204. Anon. Tamoxifen for node-negative breast cancer. FDA Drug Bull. 1990; 20:5.

205. Bianco AR, De Placido S, Gallo C et al. Adjuvant therapy with tamoxifen in operable breast cancer. Lancet. 1988; 2:1095-9. http://www.ncbi.nlm.nih.gov/pubmed/2903322?dopt=AbstractPlus

206. McGuire WL. Adjuvant therapy of node-negative breast cancer: another point of view. J Natl Cancer Inst. 1988; 80:1075-6. http://www.ncbi.nlm.nih.gov/pubmed/3411619?dopt=AbstractPlus

207. Pritchard KI. Systemic adjuvant therapy for node-negative breast cancer: proven or premature? Ann Intern Med. 1989; 111:1-4. Editorial.

208. Fisher B, Redmond C, Dimitrov NV et al. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med. 1989; 320:473-8. http://www.ncbi.nlm.nih.gov/pubmed/2644531?dopt=AbstractPlus

209. The Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med. 1989; 320:491-6. http://www.ncbi.nlm.nih.gov/pubmed/2644533?dopt=AbstractPlus

210. Mansour EG, Gray R, Shatila AH et al. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer. N Engl J Med. 1989; 320:485-90. http://www.ncbi.nlm.nih.gov/pubmed/2915651?dopt=AbstractPlus

211. Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989; 63:181-7. http://www.ncbi.nlm.nih.gov/pubmed/2910416?dopt=AbstractPlus

212. Drago F, Arditi M, Rebora A. Tamoxifen and purpuric vasculitis. Ann Intern Med. 1990; 112:965-6. http://www.ncbi.nlm.nih.gov/pubmed/2140253?dopt=AbstractPlus

213. Fernando IN, Tobias JS. Priapism in patient on tamoxifen. Lancet. 1989; 1:436. http://www.ncbi.nlm.nih.gov/pubmed/2563809?dopt=AbstractPlus

214. Larsen W, Fellowes G, Rickman LS. Life-threatening hypercalcemia and tamoxifen. Am J Med. 1990; 88:440-2. http://www.ncbi.nlm.nih.gov/pubmed/2327431?dopt=AbstractPlus

215. Rea D, Poole C, Gray R. Adjuvant tamoxifen: how long before we know how long? BMJ. 1998; 316:1518-9.

216. Stone R. NIH fends off critics of tamoxifen study. Science. 1992; 258:734. http://www.ncbi.nlm.nih.gov/pubmed/1439776?dopt=AbstractPlus

217. Andersson M, Storm HH, Mouridsen HT. Carcinogenic effects of adjuvant tamoxifen treatment and radiotherapy for early breast cancer. Acta Oncol. 1992; 31:259-63. http://www.ncbi.nlm.nih.gov/pubmed/1622643?dopt=AbstractPlus

218. Jordan VC. The role of tamoxifen in the treatment and prevention of breast cancer. Curr Probl Cancer. 1992; 16:129-76. http://www.ncbi.nlm.nih.gov/pubmed/1582240?dopt=AbstractPlus

219. Powles TJ, Hardy JR, Ashley SE et al. A pilot trial to evaluate the acute toxicity and feasibility of tamoxifen for prevention of breast cancer. Br J Cancer. 1989; 60:126-31. http://www.ncbi.nlm.nih.gov/pubmed/2679843?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2247327&blobtype=pdf

220. Powles TJ, Tillyer CR, Jones AL et al. Prevention of breast cancer with tamoxifen—an update on the Royal Marsden Hospital pilot programme. Eur J Cancer. 1990; 26:680-4. http://www.ncbi.nlm.nih.gov/pubmed/2144154?dopt=AbstractPlus

221. Costa A, Jordan VC. Meeting report: long-term antihormonal therapy for breast cancer. Eur J Cancer. 1991; 27:1479-81. http://www.ncbi.nlm.nih.gov/pubmed/1835865?dopt=AbstractPlus

222. Blackburn AM, Amiel SA, Millis RR et al. Tamoxifen and liver damage. BMJ. 1984; 289:288. http://www.ncbi.nlm.nih.gov/pubmed/6430441?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1442108&blobtype=pdf

223. Nand S. Gordon LI, Brestan E et al. Benign hepatic cyst in a patient on antiestrogen therapy for metastatic breast cancer. Cancer. 1982; 50:1882-3. http://www.ncbi.nlm.nih.gov/pubmed/7116312?dopt=AbstractPlus

224. Anon. Tamoxifen breast cancer prevention trial supporters are “voting with their feet,” NCI tells hearing; NCI has improved controls over informed consent forms. FDC Rep. Oct 26, 1992:5-6.

225. Hardell L. Tamoxifen as a risk factor for enndometrial cancer. Cancer. 1990; 66:1661. http://www.ncbi.nlm.nih.gov/pubmed/2208019?dopt=AbstractPlus

226. Jaiyesimi IA, Buzdar AU, Sahin AA et al. Carcinoma of the male breast. Ann Intern Med. 1992; 117:771-7. http://www.ncbi.nlm.nih.gov/pubmed/1416579?dopt=AbstractPlus

227. Ribeiro G, Swindell R. Adjuvant tamoxifen for male breast cancer (MBC). Br J Cancer. 1992; 65:252-4. http://www.ncbi.nlm.nih.gov/pubmed/1739625?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1977740&blobtype=pdf

228. Digenis AG, Ross CB, Morrison JG et al. Carcinoma of the male breast: a review of 41 cases. South Med J. 1990; 83:1162-7. http://www.ncbi.nlm.nih.gov/pubmed/1699287?dopt=AbstractPlus

229. Borgen PI. Male breast cancer. Semin Surg Oncol. 1991; 7:314-9. http://www.ncbi.nlm.nih.gov/pubmed/1775819?dopt=AbstractPlus

230. Donegan WL. Cancer of the breast in men. Ca Cancer J Clin. 1991; 41:339-54. http://www.ncbi.nlm.nih.gov/pubmed/1933534?dopt=AbstractPlus

231. Deacock SJ, Ohri SK. A case of synchronous bilateral separate primary male breast carcinomas. BJCP. 1991; 45:152-4.

232. Tirelli U, Tumolol S, Talamini R et al. Tamoxifen before and after orchiectomy in advanced male breast cancer. Cancer Treat Rep. 1982; 66:1882-3. http://www.ncbi.nlm.nih.gov/pubmed/7127330?dopt=AbstractPlus

233. Aisner J, Ross DD, Wiernik PH. Tamoxifen in advanced male breast cancer. Arch Intern Med. 1979; 139:480-1. http://www.ncbi.nlm.nih.gov/pubmed/435005?dopt=AbstractPlus

234. Ching CK, Smith PG, Long RG. Tamoxifen-associated hepatocellular damage and agranulocytosis. Lancet. 1992; 339:940. http://www.ncbi.nlm.nih.gov/pubmed/1348345?dopt=AbstractPlus

235. Abele R, Alberto P. Tamoxifen before orchiectomy for breast cancer in men. N Engl J Med. 1981; 305:1091-2. http://www.ncbi.nlm.nih.gov/pubmed/7278926?dopt=AbstractPlus

236. Tateishi M, Toda T, Minamisono Y et al. A 94 year old male stage IV breast cancer patient showing complete remission under tamoxifen treatment after operation. J Surg Oncol. 1992; 51:71-3. http://www.ncbi.nlm.nih.gov/pubmed/1518297?dopt=AbstractPlus

237. Kinne DW. Management of male breast cancer. Oncology. 1991; 5:45-7. http://www.ncbi.nlm.nih.gov/pubmed/1829945?dopt=AbstractPlus

238. Bezwoda WR, Hesdorffer C, Dansey R et al. Breast cancer in men: clinical features, hormone receptor status, and response to therapy. Cancer. 1987; 60:1337-40. http://www.ncbi.nlm.nih.gov/pubmed/3621116?dopt=AbstractPlus

239. Zeneca Pharmaceuticals Group, Wilmington, DE: Personal communication.

240. Neven P, De Muylder X, Van Belle Y et al. Hysteroscopic follow-up during tamoxifen treatment. Eur J Obstet Gynecol Reprod Biol. 1990; 35:235-8. http://www.ncbi.nlm.nih.gov/pubmed/2335258?dopt=AbstractPlus

241. Clark S. Prophylactic tamoxifen. Lancet. 1993; 342:168.

242. Costa A. Tamoxifen trial in healthy women at risk of breast cancer. Lancet. 1993; 342:444. http://www.ncbi.nlm.nih.gov/pubmed/8101951?dopt=AbstractPlus

243. Goodare H. Tamoxifen trial in healthy women at risk of breast cancer. Lancet. 1993; 342:444. http://www.ncbi.nlm.nih.gov/pubmed/8101952?dopt=AbstractPlus

244. Hard GC, Williams GM, Iatropoulos MJ. Tamoxifen and liver cancer. Lancet. 1993; 342:444-5. http://www.ncbi.nlm.nih.gov/pubmed/8101953?dopt=AbstractPlus

245. Phillips DH, Venitt S. Safety of prophylactic tamoxifen. Lancet. 1993; 341:1485-6. http://www.ncbi.nlm.nih.gov/pubmed/8099187?dopt=AbstractPlus

246. Powles TJ. The case for clinical trials of tamoxifen for prevention of breast cancer. Lancet. 1992; 340:1145-7. http://www.ncbi.nlm.nih.gov/pubmed/1359221?dopt=AbstractPlus

247. Fugh-Berman A, Epstein S. Tamoxifen: disease prevention or disease substitution? Lancet. 1992; 340:1143-5. Editorial.

248. Ernst E, Resch KL, Fialka V. Tamoxifen and prevention. Lancet. 1993; 341:694-5. http://www.ncbi.nlm.nih.gov/pubmed/8095599?dopt=AbstractPlus

249. Fugh-Berman A, Epstein SS. Tamoxifen and prevention. Lancet. 1993; 341:695. http://www.ncbi.nlm.nih.gov/pubmed/8095600?dopt=AbstractPlus

250. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther. 2000; 42:83-92. http://www.ncbi.nlm.nih.gov/pubmed/10994034?dopt=AbstractPlus

251. Ribeiro G. Male breast carcinoma—a review of 301 cases from the Christie Hospital and Holt Radium Institute, Manchester. Br J Cancer. 1985; 51:115-9. http://www.ncbi.nlm.nih.gov/pubmed/3966965?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1976811&blobtype=pdf

252. Ribeiro G. Tamoxifen in the treatment of male breast carcinoma. Clin Radiol. 1983; 34:625-8. http://www.ncbi.nlm.nih.gov/pubmed/6673881?dopt=AbstractPlus

253. Early Breast Cancer Trialists’ Collaborative Group. Part 1: Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31 000 recurrences and 24 000 deaths among 75 000 women. Lancet. 1992; 339:1-15. http://www.ncbi.nlm.nih.gov/pubmed/1345950?dopt=AbstractPlus

254. Early Breast Cancer Trialists’ Collaborative Group. Part 2: Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31 000 recurrences and 24 000 deaths among 75 000 women. Lancet. 1992; 339:71-85. http://www.ncbi.nlm.nih.gov/pubmed/1345869?dopt=AbstractPlus

255. Anon. Adjuvant systemic therapy for early breast cancer. Lancet. 1992; 339:27. http://www.ncbi.nlm.nih.gov/pubmed/1345955?dopt=AbstractPlus

256. National Cancer Institute (NCI). NCI issues clinical announcement about long-term use of tamoxifen in breast cancer treatment. Bethesda, MD. 1995 Nov 30. Press release.

257. National Cancer Institute. Adjuvant therapy of breast cancer—tamoxifen update. Bethesda, MD. 1995 Nov 30. Clinical announcement.

258. Breast cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1998 Dec.

259. Kedar RP, Bourne TH, Powles TJ et al. Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial. Lancet. 1994; 343:1818-21.

260. Goldberg RM, Loprinzi CL, O’Fallon JR et al. Transdermal clonidine for ameliorating tamoxifen-induced hot flashes. J Clin Oncol. 1994; 12:155-8. http://www.ncbi.nlm.nih.gov/pubmed/8270972?dopt=AbstractPlus

261. Love RR, Surawicz RS, Williams EC. Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy. Arch Intern Med. 1992; 152:317-20. http://www.ncbi.nlm.nih.gov/pubmed/1739360?dopt=AbstractPlus

262. Love RR, Cameron L, Connell BL et al. Symptoms associated with tamoxifen treatment in postmenopausal women. Arch Intern Med. 1991; 151:1842-7. http://www.ncbi.nlm.nih.gov/pubmed/1888251?dopt=AbstractPlus

263. McDonald CC, Stewart HJ. Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. BMJ. 1991; 303:435-7. http://www.ncbi.nlm.nih.gov/pubmed/1912833?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1670561&blobtype=pdf

264. Rutqvist LE, Mattsson A. Cardiac and thromboembolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen. J Natl Cancer Inst. 1993; 85:1398-1406. http://www.ncbi.nlm.nih.gov/pubmed/8350363?dopt=AbstractPlus

265. Love RR, Mazess RB, Barden HS et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med. 1992; 326:852-6. http://www.ncbi.nlm.nih.gov/pubmed/1542321?dopt=AbstractPlus

266. Kristensen B, Ejlertsen B, Dalgaard P et al. Tamoxifen and bone metabolism in postmenopausal low—risk breast cancer patients: a randomized study. J Clin Oncol. 1994; 12:992-7. http://www.ncbi.nlm.nih.gov/pubmed/8164053?dopt=AbstractPlus

267. Love RR, Barden HS, Mazess RB et al. Effect of tamoxifen on lumbar spine bone mineral density in postmenopausal women after 5 years. Arch Intern Med. 1994; 154:2585-8. http://www.ncbi.nlm.nih.gov/pubmed/7979855?dopt=AbstractPlus

268. Bentley CR, Davies G, Aclimandos WA. Tamoxifen retinopathy: a rare but serious complication. BMJ. 1992; 304:495-6. http://www.ncbi.nlm.nih.gov/pubmed/1312376?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1881086&blobtype=pdf

269. National Cancer Institute (NCI). Breast Cancer Prevention Trial shows major benefit, some risk. Bethesda, MD. 1998 Apr 6. Press release.

270. National Cancer Institute (NCI). Questions & answers: the Breast Cancer Prevention Trial. Bethesda, MD. 1998 Sep 14.

271. Prevention of breast cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1998 Nov.

272. O’Shaughnessy JA. Chemoprevention of breast cancer. JAMA. 1996; 275:1349-53. http://www.ncbi.nlm.nih.gov/pubmed/8614122?dopt=AbstractPlus

273. Powles TJ, Jones AL, Ashley SE et al. The Royal Marsden Hospital pilot tamoxifen chemoprevention trial. Breast Cancer Res Treat. 1994; 31:73-82. http://www.ncbi.nlm.nih.gov/pubmed/7981459?dopt=AbstractPlus

274. Kedar RP, Bourne TH, Powles TJ et al. Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial. Lancet. 1994; 343:1318-21. http://www.ncbi.nlm.nih.gov/pubmed/7910323?dopt=AbstractPlus

275. Powles TJ, Hickish T, Kanis JA et al. Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol. 1996; 14:78-84. http://www.ncbi.nlm.nih.gov/pubmed/8558225?dopt=AbstractPlus

276. Harris JR, Lippman ME, Veronesi U et al. Breast cancer (3). N Engl J Med. 1992; 327:473-80. http://www.ncbi.nlm.nih.gov/pubmed/1625737?dopt=AbstractPlus

277. Ford LG, Johnson KA. Tamoxifen Breast Cancer Prevention Trial: an update. Prog Clin Biol Res. 1997; 396:271-82. http://www.ncbi.nlm.nih.gov/pubmed/9108604?dopt=AbstractPlus

278. Redmond CK, Costantino JP. Design and current status of the NSABP breast cancer prevention trial. Recent Results Cancer Res. 1996; 140:309-17. http://www.ncbi.nlm.nih.gov/pubmed/8787073?dopt=AbstractPlus

279. Jordan VC. An overview of considerations for the testing of tamoxifen as a preventive for breast cancer. Ann NY Acad Sci. 1995; 768:141-7. http://www.ncbi.nlm.nih.gov/pubmed/8526343?dopt=AbstractPlus

280. Vogel VG, Saenz M. Tamoxifen for the prevention of breast cancer: yes. In: DeVita VT, Hellman S, Rosenberg SA, eds. Important advances in oncology. Philadelphia: JB Lippincott Company; 1995:187-200.

281. DeGregorio MW, Maenpaa JU, Wiebe VJ. Tamoxifen for the prevention of breast cancer: no. In: DeVita VT, Hellman S, Rosenberg SA, eds. Important advances in oncology. Philadelphia: JB Lippincott Company; 1995:175-85.

282. Anon. Nolvadex vs. Evista breast cancer prevention trial proposed by NSABP. FDC Rep. Apr 13, 1998:7-8.

283. Jordan VC. Tamoxifen: the herald of a new era of preventive therapeutics. J Natl Cancer Inst. 1997; 89:747-9. http://www.ncbi.nlm.nih.gov/pubmed/9182965?dopt=AbstractPlus

284. Ault A, Bradbury J. Experts argue about tamoxifen prevention trial. Lancet. 1998; 351:1107. http://www.ncbi.nlm.nih.gov/pubmed/9660593?dopt=AbstractPlus

285. Morris K. IBIS tamoxifen trial to continue. Lancet. 1998; 351:1493. http://www.ncbi.nlm.nih.gov/pubmed/9605815?dopt=AbstractPlus

286. Hankinson SE, Willett WC, Colditz GA et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet. 1998; 351:1393-6. http://www.ncbi.nlm.nih.gov/pubmed/9593409?dopt=AbstractPlus

287. Holly J. Insulin-like growth factor-I and new opportunities for cancer prevention. Lancet. 1998; 351:1373-5. http://www.ncbi.nlm.nih.gov/pubmed/9593403?dopt=AbstractPlus

288. Anon. Zeneca Nolvadex: Tamoxifen NDA supplement filed. FDC Rep. 1998 May 4:in brief.

289. Reviewer comments (personal observations).

290. Wickerham DL. Chemoprevention with tamoxifen reduces breast cancer incidence: results from NSABP P-1. Online coverage from the American Society of Clinical Oncology, May 16-19, 1998, on Medscape.

291. Fisher B, Dignam J, Bryant J et al. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst. 1996; 88:1529-42. http://www.ncbi.nlm.nih.gov/pubmed/8901851?dopt=AbstractPlus

292. Anon. SERM breast cancer prevention is subclinical disease therapy—ASCO. FDC Rep. 1998 May 25.

293. Fisher B, Costantino JP, Wickerham DL et al. Tamoxifen for the prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 1998; 90:1371-88. http://www.ncbi.nlm.nih.gov/pubmed/9747868?dopt=AbstractPlus

294. Veronesi U, Maisonneuve P, Costa A et al. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Lancet. 1998; 352:93-7. http://www.ncbi.nlm.nih.gov/pubmed/9672273?dopt=AbstractPlus

295. Powles T, Eeles R, Ashley S et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet. 1998; 352:98-101. http://www.ncbi.nlm.nih.gov/pubmed/9672274?dopt=AbstractPlus

296. Anon. Interim reports published on two European breast cancer prevention trials. Bethesda, MD: National Cancer Institute; 1998 Jul 9.

297. Pritchard KI. Is tamoxifen effective in prevention of breast cancer? Lancet. 1998; 352:80-1.

298. Fisher B, Costantino JP, Redmond CK et al. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst. 1994; 86:527-37. http://www.ncbi.nlm.nih.gov/pubmed/8133536?dopt=AbstractPlus

299. Goel V. Tamoxifen and breast cancer prevention: What should you tell your patients? CMAJ. 1998; 158:1615-7.

300. Bruzzi P. Tamoxifen for the prevention of breast cancer. Important questions remain unanswered, and existing trials should continue. BMJ. 1998; 316:1181-2. http://www.ncbi.nlm.nih.gov/pubmed/9552991?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1112979&blobtype=pdf

301. Karp SE, Tonin PN, Begin LR et al. Influence of BRCA1 mutations on nuclear grade and estrogen receptor status of breast carcinoma in Ashkenazi Jewish women. Cancer. 1997; 80:435-41. http://www.ncbi.nlm.nih.gov/pubmed/9241077?dopt=AbstractPlus

302. Anon. Nolvadex BRCA1/2 study IRB approval expected by October. FDC Rep. September 21, 1998:16.

303. National Cancer Institute (NCI). Tamoxifen and breast cancer prevention: assessing risk. Bethesda, MD. 1998 Sep 14.

304. Anon. Nolvadex breast cancer prevention registry should be developed. FDC Rep. September 7, 1998.

305. Trock BJ. Breast cancer in African American women: epidemiology and tumor biology. Breast Cancer Res Treat. 1996; 40:11-24. http://www.ncbi.nlm.nih.gov/pubmed/8888149?dopt=AbstractPlus

306. Elledge RM, Clark GM, Chamness GC et al. Tumor biologic factors and breast cancer prognosis among white, Hispanic, and black women in the United States. J Natl Cancer Inst. 1994; 86:705-12. http://www.ncbi.nlm.nih.gov/pubmed/7908990?dopt=AbstractPlus

307. Oncologic Drugs Advisory Committee Meeting. 58th meeting. Bethesda, MD: Food and Drug Administration; 1998 Sep 2.

308. Food and Drug Administration. Tamoxifen approved for reducing breast cancer incidence. Rockville, MD. 1998 Oct 29. Press release.

309. Zeneca Pharmaceuticals. Landmark findings from Breast Cancer Prevention Trial lead FDA to approve Zeneca s Nolvadex (tamoxifen citrate) for the reduction of breast cancer in women at high risk. Wilmington, DE. 1998 Oct 29. Press release.

310. Private Citizen. FDA s approval of tamoxifen to reduce incidence of breast cancer in healthy women puts women at risk. Washington, DC. 1998 Oct 29. Press release.

311. Robinson E, Kimmick GG, Muss HB. Tamoxifen in postmenopausal women: a safety perspective. Drugs Aging. 1996; 8:329-37. http://www.ncbi.nlm.nih.gov/pubmed/8935395?dopt=AbstractPlus

312. Stewart PJ, Stern PH. Effects of the antiestrogens tamoxifen and clomiphene on bone resorption in vitro. Endocrinology. 1986; 118:125-31. http://www.ncbi.nlm.nih.gov/pubmed/3455681?dopt=AbstractPlus

313. Turner RT, Wakley GK, Hannon KS et al. Tamoxifen inhibits osteoclast-mediated resorption of trabecular bone in ovarian hormone-deficient rats. Endocrinology. 1988; 122:1146-50. http://www.ncbi.nlm.nih.gov/pubmed/3342747?dopt=AbstractPlus

314. Turner RT, Wakley GK, Hannon KS et al. Tamoxifen prevents the skeletal effects of ovarian hormone deficiency in rats. J Bone Miner Res. 1987; 2:449-56. http://www.ncbi.nlm.nih.gov/pubmed/3455628?dopt=AbstractPlus

315. Jordan VC, Phelps E, Lindgren JU. Effects of anti-estrogens on bone in castrated and intact female rats. Breast Cancer Res Treat. 1987; 10:31-5. http://www.ncbi.nlm.nih.gov/pubmed/3689979?dopt=AbstractPlus

316. Grey AB, Stapleton JP, Evans MC et al. The effect of the antiestrogen tamoxifen on bone mineral density in normal late menopausal women. Am J Med. 1995; 99:636-41. http://www.ncbi.nlm.nih.gov/pubmed/7503087?dopt=AbstractPlus

317. Davidson NE. Tamoxifen—panacea or Pandora’s box? N Engl J Med. 1992; 326:885-6.

318. Dewar JA, Horobin JM, Preece PE et al. Long term effects of tamoxifen on blood lipid values in breast cancer. BMJ. 1992; 305:225-6. http://www.ncbi.nlm.nih.gov/pubmed/1392827?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1882673&blobtype=pdf

319. Love RR, Newcomb PA, Wiebe DA et al. Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer. J Natl Cancer Inst. 1990; 82:1327-32. http://www.ncbi.nlm.nih.gov/pubmed/2199681?dopt=AbstractPlus

320. Love RR, Wiebe DA, Newcomb PA et al. Effects of tamoxifen on cardiovascular risk factors in postmenopausal women. Ann Intern Med. 1991; 115:860-4. http://www.ncbi.nlm.nih.gov/pubmed/1952472?dopt=AbstractPlus

321. McDonald CC, Alexander FE, Whyte BW et al. Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomised trial. BMJ. 1995; 311:977-80. http://www.ncbi.nlm.nih.gov/pubmed/7580638?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2550987&blobtype=pdf

322. Costantino JP, Kuller LH, Ives DG et al. Coronary heart disease mortality and adjuvant tamoxifen therapy. J Natl Cancer Inst. 1997; 89:776-82. http://www.ncbi.nlm.nih.gov/pubmed/9182975?dopt=AbstractPlus

323. Pollak M, Costantino J, Polychronakos C et al. Effect of tamoxifen on serum insulinlike growth factor I levels in stage I breast cancer patients. J Natl Cancer Inst. 1990; 82:1693-7. http://www.ncbi.nlm.nih.gov/pubmed/2231756?dopt=AbstractPlus

324. Kanel KT, Wolmark N, Thompson PD. Delayed severe hypertriglyceridemia from tamoxifen. N Engl J Med. 1997; 337:281. http://www.ncbi.nlm.nih.gov/pubmed/9229698?dopt=AbstractPlus

325. Mikhailidis DP, Ganotakis ES, Georgoulias VA et al. Tamoxifen-induced hypertriglyceridemia: seven case reports and suggestions for remedial action. Oncol Rep. 1997; 4:625-8. http://www.ncbi.nlm.nih.gov/pubmed/21590112?dopt=AbstractPlus

326. Gorin MB, Day R, Costantino JP et al. Long-term tamoxifen citrate use and potential ocular toxicity. Am J Ophthalmol. 1998; 125:493-501. http://www.ncbi.nlm.nih.gov/pubmed/9559735?dopt=AbstractPlus

327. Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet. 1998; 351:1451-67. http://www.ncbi.nlm.nih.gov/pubmed/9605801?dopt=AbstractPlus

328. Swedish Breast Cancer Cooperative Group. Randomized trial of two versus five years of adjuvant tamoxifen for postmenopausal early stage breast cancer. J Natl Cancer Inst. 1996; 88:1543-9. http://www.ncbi.nlm.nih.gov/pubmed/8901852?dopt=AbstractPlus

329. Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med. 1998; 339:1609-18. http://www.ncbi.nlm.nih.gov/pubmed/9828250?dopt=AbstractPlus

330. Purvis J. Dear doctor letter regarding warning information on serious or fatal adverse effects among women receiving tamoxifen for risk reduction. Wilmington, DE: AstraZeneca Pharmaceuticals; 2002 May 15.

332. Burstein HJ, Temin S, Anderson H et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J Clin Oncol. 2014; 32:2255-69. http://www.ncbi.nlm.nih.gov/pubmed/24868023?dopt=AbstractPlus

333. Gray RG, Rea D, Handley K et al. aTTom: long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol. 2013 (Suppl 18): 5. http://ascopubs.org/doi/abs/10.1200/jco.2013.31.18_suppl.5

334. Burstein HJ, Prestrud AA, Seidenfeld J et al. American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol. 2010; 28:3784-96. http://www.ncbi.nlm.nih.gov/pubmed/20625130?dopt=AbstractPlus

335. Davies C, Pan H, Godwin J et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013; 381:805-16. http://www.ncbi.nlm.nih.gov/pubmed/23219286?dopt=AbstractPlus

336. Rugo HS, Rumble RB, Macrae E et al. Endocrine Therapy for Hormone Receptor-Positive Metastatic Breast Cancer: American Society of Clinical Oncology Guideline. J Clin Oncol. 2016; 34:3069-103. http://www.ncbi.nlm.nih.gov/pubmed/27217461?dopt=AbstractPlus

337. Visvanathan K, Hurley P, Bantug E et al. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013; 31:2942-62. http://www.ncbi.nlm.nih.gov/pubmed/23835710?dopt=AbstractPlus

338. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology (NCCN Guidelines): breast cancer. Version 1.2018.

339. Goetz MP, Sangkuhl K, Guchelaar HJ et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy. Clin Pharmacol Ther. 2018; 103:770-777. http://www.ncbi.nlm.nih.gov/pubmed/29385237?dopt=AbstractPlus

342. Zeneca Pharmaceuticals. Nolvadex (tamoxifen citrate) prescribing information. Wilmington, DE; 1998 Oct.

343. Hilner BE, Ingle JN, Chelbowski RT et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003; 21:4042-57. http://www.ncbi.nlm.nih.gov/pubmed/12963702?dopt=AbstractPlus

344. Wellington K, Faulds DM. Anastrozole: in early breast cancer. Drugs. 2002; 62:2483-90; discussion 2491-2. http://www.ncbi.nlm.nih.gov/pubmed/12421108?dopt=AbstractPlus

345. The ATAC Trialists’ Group. Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the ‘ArimidexTM and Tamoxifen Alone or in Combination’ (ATAC) trial. Br J Cancer. 2001; 85:317-24. http://www.ncbi.nlm.nih.gov/pubmed/11487258?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2364083&blobtype=pdf

346. Thota K, Prasad K, Basaveswara Rao MV. Detection of Cytochrome P450 Polymorphisms in Breast Cancer Patients May Impact on Tamoxifen Therapy. Asian Pac J Cancer Prev. 2018; 19:343-350. http://www.ncbi.nlm.nih.gov/pubmed/29479969?dopt=AbstractPlus

347. Damkier P, Kjærsgaard A, Barker KA et al. CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset. Sci Rep. 2017; 7:7727. http://www.ncbi.nlm.nih.gov/pubmed/28798474?dopt=AbstractPlus

348. Cronin-Fenton DP, Damkier P. Tamoxifen and CYP2D6: A Controversy in Pharmacogenetics. Adv Pharmacol. 2018; 83:65-91. http://www.ncbi.nlm.nih.gov/pubmed/29801584?dopt=AbstractPlus

349. Klopp-Schulze L, Joerger M, Wicha SG et al. Exploiting Pharmacokinetic Models of Tamoxifen and Endoxifen to Identify Factors Causing Subtherapeutic Concentrations in Breast Cancer Patients. Clin Pharmacokinet. 2018; 57:229-242. http://www.ncbi.nlm.nih.gov/pubmed/28540639?dopt=AbstractPlus

350. Nakamura T, Toshimoto K, Lee W et al. Application of PBPK Modeling and Virtual Clinical Study Approaches to Predict the Outcomes of CYP2D6 Genotype-Guided Dosing of Tamoxifen. CPT Pharmacometrics Syst Pharmacol. 2018; 7:474-482. http://www.ncbi.nlm.nih.gov/pubmed/29920987?dopt=AbstractPlus

351. Del Re M, Rofi E, Citi V et al. Should CYP2D6 be genotyped when treating with tamoxifen?. Pharmacogenomics. 2016; 17:1967-1969. http://www.ncbi.nlm.nih.gov/pubmed/27883289?dopt=AbstractPlus

352. Goetz MP, Schaid DJ, Wickerham DL et al. Evaluation of CYP2D6 and efficacy of tamoxifen and raloxifene in women treated for breast cancer chemoprevention: results from the NSABP P1 and P2 clinical trials. Clin Cancer Res. 2011; 17:6944-51. http://www.ncbi.nlm.nih.gov/pubmed/21880792?dopt=AbstractPlus

353. Damkier P. Don't think twice it's all right: tamoxifen and CYP2D6 genotyping in the treatment of breast cancer patients. Pharmacogenomics. 2017; 18:753-754. http://www.ncbi.nlm.nih.gov/pubmed/28592184?dopt=AbstractPlus

354. Hertz DL, Deal A, Ibrahim JG et al. Tamoxifen Dose Escalation in Patients With Diminished CYP2D6 Activity Normalizes Endoxifen Concentrations Without Increasing Toxicity. Oncologist. 2016; 21:795-803. http://www.ncbi.nlm.nih.gov/pubmed/27226358?dopt=AbstractPlus

355. Madlensky L, Natarajan L, Tchu S et al. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther. 2011; 89:718-25. http://www.ncbi.nlm.nih.gov/pubmed/21430657?dopt=AbstractPlus

356. Regan MM, Leyland-Jones B, Bouzyk M et al. CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial. J Natl Cancer Inst. 2012; 104:441-51. http://www.ncbi.nlm.nih.gov/pubmed/22395644?dopt=AbstractPlus

357. Rae JM, Drury S, Hayes DF et al. CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst. 2012; 104:452-60. http://www.ncbi.nlm.nih.gov/pubmed/22395643?dopt=AbstractPlus

358. Goetz MP, Suman VJ, Hoskin TL et al. CYP2D6 metabolism and patient outcome in the Austrian Breast and Colorectal Cancer Study Group trial (ABCSG) 8. Clin Cancer Res. 2013; 19:500-7. http://www.ncbi.nlm.nih.gov/pubmed/23213055?dopt=AbstractPlus

359. Saladores P, Mürdter T, Eccles D et al. Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer. Pharmacogenomics J. 2015; 15:84-94. http://www.ncbi.nlm.nih.gov/pubmed/25091503?dopt=AbstractPlus

360. Province MA, Goetz MP, Brauch H et al. CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations. Clin Pharmacol Ther. 2014; 95:216-27. http://www.ncbi.nlm.nih.gov/pubmed/24060820?dopt=AbstractPlus

361. Brauch H, Schroth W, Goetz MP et al. Tamoxifen use in postmenopausal breast cancer: CYP2D6 matters. J Clin Oncol. 2013; 31:176-80. http://www.ncbi.nlm.nih.gov/pubmed/23091108?dopt=AbstractPlus

362. Nakamura Y, Ratain MJ, Cox NJ et al. Re: CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the Breast International Group 1-98 trial. J Natl Cancer Inst. 2012; 104:1264; author reply 1266-8. http://www.ncbi.nlm.nih.gov/pubmed/22851270?dopt=AbstractPlus

363. Swain SM, Wilson JW, Mamounas EP et al. Estrogen receptor status of primary breast cancer is predictive of estrogen receptor status of contralateral breast cancer. J Natl Cancer Inst. 2004; 96:516-23. http://www.ncbi.nlm.nih.gov/pubmed/15069113?dopt=AbstractPlus

364. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20; 365:1687-717. http://www.ncbi.nlm.nih.gov/pubmed/15894097?dopt=AbstractPlus

365. Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Davies C, Godwin J et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011; 378:771-84. http://www.ncbi.nlm.nih.gov/pubmed/21802721?dopt=AbstractPlus

366. Tremont A, Lu J, Cole JT. Endocrine Therapy for Early Breast Cancer: Updated Review. Ochsner J. 2017; 17:405-411. http://www.ncbi.nlm.nih.gov/pubmed/29230126?dopt=AbstractPlus

367. Sparano JA, Gray RJ, Makower DF et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. 2018; 379:111-121. http://www.ncbi.nlm.nih.gov/pubmed/29860917?dopt=AbstractPlus

368. Henry NL, Somerfield MR, Abramson VG et al. Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer: American Society of Clinical Oncology Endorsement of Cancer Care Ontario Guideline Recommendations. J Clin Oncol. 2016; 34:2303-11. http://www.ncbi.nlm.nih.gov/pubmed/27001586?dopt=AbstractPlus

369. Krop I, Ismaila N, Andre F et al. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update. J Clin Oncol. 2017; 35:2838-2847. http://www.ncbi.nlm.nih.gov/pubmed/28692382?dopt=AbstractPlus

370. Fisher B, Costantino JP, Wickerham DL et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 2005; 97:1652-62. http://www.ncbi.nlm.nih.gov/pubmed/16288118?dopt=AbstractPlus

371. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology (NCCN Guidelines): breast cancer risk reduction. Version 1.2019.

372. Powles TJ, Ashley S, Tidy A et al. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst. 2007; 99:283-90. http://www.ncbi.nlm.nih.gov/pubmed/17312305?dopt=AbstractPlus

373. Cuzick J, Sestak I, Cawthorn S et al. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 2015; 16:67-75. http://www.ncbi.nlm.nih.gov/pubmed/25497694?dopt=AbstractPlus

374. Veronesi U, Maisonneuve P, Rotmensz N et al. Tamoxifen for the prevention of breast cancer: late results of the Italian Randomized Tamoxifen Prevention Trial among women with hysterectomy. J Natl Cancer Inst. 2007; 99:727-37. http://www.ncbi.nlm.nih.gov/pubmed/17470740?dopt=AbstractPlus

375. Land SR, Wickerham DL, Costantino JP et al. Patient-reported symptoms and quality of life during treatment with tamoxifen or raloxifene for breast cancer prevention: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006; 295:2742-51. http://www.ncbi.nlm.nih.gov/pubmed/16754728?dopt=AbstractPlus

376. Vogel VG, Costantino JP, Wickerham DL et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006; 295:2727-41. http://www.ncbi.nlm.nih.gov/pubmed/16754727?dopt=AbstractPlus

377. King MC, Wieand S, Hale K et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA. 2001; 286:2251-6. http://www.ncbi.nlm.nih.gov/pubmed/11710890?dopt=AbstractPlus

378. Giordano SH. Breast Cancer in Men. N Engl J Med. 2018; 378:2311-2320. http://www.ncbi.nlm.nih.gov/pubmed/29897847?dopt=AbstractPlus

379. Johnson MD, Zuo H, Lee KH et al. Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat. 2004; 85:151-9. http://www.ncbi.nlm.nih.gov/pubmed/15111773?dopt=AbstractPlus

380. Kiyotani K, Mushiroda T, Nakamura Y et al. Pharmacogenomics of tamoxifen: roles of drug metabolizing enzymes and transporters. Drug Metab Pharmacokinet. 2012; 27:122-31. http://www.ncbi.nlm.nih.gov/pubmed/22041137?dopt=AbstractPlus

381. Klein DJ, Thorn CF, Desta Z et al. PharmGKB summary: tamoxifen pathway, pharmacokinetics. Pharmacogenet Genomics. 2013; 23:643-7. http://www.ncbi.nlm.nih.gov/pubmed/23962908?dopt=AbstractPlus

382. Johänning J, Kröner P, Thomas M et al. The formation of estrogen-like tamoxifen metabolites and their influence on enzyme activity and gene expression of ADME genes. Arch Toxicol. 2018; 92:1099-1112. http://www.ncbi.nlm.nih.gov/pubmed/29285606?dopt=AbstractPlus

383. de Vries Schultink AH, Zwart W, Linn SC et al. Effects of Pharmacogenetics on the Pharmacokinetics and Pharmacodynamics of Tamoxifen. Clin Pharmacokinet. 2015; 54:797-810. http://www.ncbi.nlm.nih.gov/pubmed/25940823?dopt=AbstractPlus

384. Drögemöller BI, Wright GEB, Shih J et al. CYP2D6 as a treatment decision aid for ER-positive non-metastatic breast cancer patients: a systematic review with accompanying clinical practice guidelines. Breast Cancer Res Treat. 2018; http://www.ncbi.nlm.nih.gov/pubmed/30411242?dopt=AbstractPlus

385. Hansten PD. The Underrated Risks of Tamoxifen Drug Interactions. Eur J Drug Metab Pharmacokinet. 2018; 43:495-508. http://www.ncbi.nlm.nih.gov/pubmed/29637493?dopt=AbstractPlus

386. Lien EA, Anker G, Lønning PE et al. Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide. Cancer Res. 1990; 50:5851-7. http://www.ncbi.nlm.nih.gov/pubmed/2393854?dopt=AbstractPlus

387. Gryn SE, Teft WA, Kim RB. Profound reduction in the tamoxifen active metabolite endoxifen in a patient on phenytoin for epilepsy compared with a CYP2D6 genotype matched cohort. Pharmacogenet Genomics. 2014; 24:367-9. http://www.ncbi.nlm.nih.gov/pubmed/24915025?dopt=AbstractPlus

388. Schroth W, Goetz MP, Hamann U et al. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA. 2009; 302:1429-36. http://www.ncbi.nlm.nih.gov/pubmed/19809024?dopt=AbstractPlus

389. Goetz MP, Rae JM, Suman VJ et al. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol. 2005; 23:9312-8. http://www.ncbi.nlm.nih.gov/pubmed/16361630?dopt=AbstractPlus

390. Schroth W, Antoniadou L, Fritz P et al. Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J Clin Oncol. 2007; 25:5187-93. http://www.ncbi.nlm.nih.gov/pubmed/18024866?dopt=AbstractPlus

391. Vogel VG, Costantino JP, Wickerham DL et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. Cancer Prev Res (Phila). 2010; 3:696-706. http://www.ncbi.nlm.nih.gov/pubmed/20404000?dopt=AbstractPlus

392. Paridaens RJ, Dirix LY, Beex LV et al. Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J Clin Oncol. 2008; 26:4883-90. http://www.ncbi.nlm.nih.gov/pubmed/18794551?dopt=AbstractPlus

393. Nabholtz JM, Buzdar A, Pollak M et al. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. J Clin Oncol. 2000; 18:3758-67. http://www.ncbi.nlm.nih.gov/pubmed/11078488?dopt=AbstractPlus

394. Bonneterre J, Thürlimann B, Robertson JF et al. Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J Clin Oncol. 2000; 18:3748-57. http://www.ncbi.nlm.nih.gov/pubmed/11078487?dopt=AbstractPlus

395. Gibson L, Lawrence D, Dawson C et al. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst Rev. 2009; :CD003370. http://www.ncbi.nlm.nih.gov/pubmed/19821307?dopt=AbstractPlus

a. AHFS drug information. McEvoy GK, ed. Tamoxifen citrate. Bethesda, MD: American Society of Health-System Pharmacists; Updated 2019. From AHFS DI website (www.ahfsdruginformation.com).