This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (226)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in JAMA  Topic Collections  • Genetic Disorders  • Women's Health, Other  • Oncology  • Breast Cancer  • Alert me on articles by topic

National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial

Mary-Claire King, PhD; Sam Wieand, PhD; Kathryn Hale, BS; Ming Lee, PhD; Tom Walsh, PhD; Kelly Owens, PhD; Jonathan Tait, MD, PhD; Leslie Ford, MD; Barbara K. Dunn, MD, PhD; Joseph Costantino, DrPH; Lawrence Wickerham, MD; Norman Wolmark, MD; Bernard Fisher, MD

JAMA. 2001;286:2251-2256.

Context  Among cancer-free women aged 35 years or older, tamoxifen reduced the incidence of estrogen receptor (ER)–positive but not ER-negative breast cancer. The effect of tamoxifen on breast cancer incidence among women at extremely high risk due to inherited BRCA1 or BRCA2 mutations is unknown.

Objective  To evaluate the effect of tamoxifen on incidence of breast cancer among cancer-free women with inherited BRCA1 or BRCA2 mutations.

Design, Setting, and Participants  Genomic analysis of BRCA1 and BRCA2 for 288 women who developed breast cancer after entry into the randomized, double-blind Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel Project (between April 1, 1992, and September 30, 1999).

Main Outcome Measure  Among women with BRCA1 or BRCA2 mutations, incidence of breast cancer among those who were receiving tamoxifen vs incidence of breast cancer among those receiving placebo.

Results  Of the 288 breast cancer cases, 19 (6.6%) inherited disease-predisposing BRCA1 or BRCA2 mutations. Of 8 patients with BRCA1 mutations, 5 received tamoxifen and 3 received placebo (risk ratio, 1.67; 95% confidence interval, 0.32-10.70). Of 11 patients with BRCA2 mutations, 3 received tamoxifen and 8 received placebo (risk ratio, 0.38; 95% confidence interval, 0.06-1.56). From 10 studies, including this one, 83% of BRCA1 breast tumors were ER-negative, whereas 76% of BRCA2 breast tumors were ER-positive.

Conclusion  Tamoxifen reduced breast cancer incidence among healthy BRCA2 carriers by 62%, similar to the reduction in incidence of ER-positive breast cancer among all women in the Breast Cancer Prevention Trial. In contrast, tamoxifen use beginning at age 35 years or older did not reduce breast cancer incidence among healthy women with inherited BRCA1 mutations. Whether tamoxifen use at a younger age would reduce breast cancer incidence among healthy women with BRCA1 mutations remains unknown.

Author Affiliations: Departments and Medicine and Genomic Sciences (Drs King, Lee, Walsh, and Owens and Ms Hale) and Laboratory Medicine (Dr Tait), University of Washington, Seattle; and National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh, Pittsburgh, Pa (Drs Wieand, Costantino, Wickerham, Wolmark, and Fisher); and National Cancer Institute, Bethesda, Md (Drs Ford and Dunn).

RELATED ARTICLE

November 14, 2001
JAMA. 2001;286(18):2337-2338.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Management of breast cancer--Part I
Turner and Jones
BMJ 2008;337:a421-a421.
FULL TEXT  

Risk-Reducing Salpingo-Oophorectomy for the Prevention of BRCA1- and BRCA2-Associated Breast and Gynecologic Cancer: A Multicenter, Prospective Study
Kauff et al.
JCO 2008;26:1331-1337.
ABSTRACT | FULL TEXT  

The Predominant Role of Surgery in the Prevention and New Trends in the Surgical Treatment of Women With BRCA1/2 Mutations
Fatouros et al.
Ann. Surg. Oncol. 2008;15:21-33.
ABSTRACT | FULL TEXT  

Screening and Follow-up of the Patient at High Risk for Breast Cancer
Willey and Cocilovo
Obstet Gynecol 2007;110:1404-1416.
ABSTRACT | FULL TEXT  

Molecular Basis for Estrogen Receptor {alpha} Deficiency in BRCA1-Linked Breast Cancer
Hosey et al.
JNCI J Natl Cancer Inst 2007;99:1683-1694.
ABSTRACT | FULL TEXT  

Management of an Inherited Predisposition to Breast Cancer
Robson and Offit
NEJM 2007;357:154-162.
FULL TEXT  

Risk-Reducing Salpingo-Oophorectomy in Patients With Germline Mutations in BRCA1 or BRCA2
Kauff and Barakat
JCO 2007;25:2921-2927.
ABSTRACT | FULL TEXT  

Risk Communication During Screening for Genomic Breast Cancer Susceptibility
Gramling and Vidrine
AMERICAN JOURNAL OF LIFESTYLE MEDICINE 2007;1:54-58.
ABSTRACT  

BRCA1 and BRCA2 Mutation Carriers, Oral Contraceptive Use, and Breast Cancer Before Age 50
Haile et al.
Cancer Epidemiol. Biomarkers Prev. 2006;15:1863-1870.
ABSTRACT | FULL TEXT  

Selective Estrogen Receptor Modulators and Prevention of Invasive Breast Cancer
Gradishar and Cella
JAMA 2006;295:2784-2786.
FULL TEXT  

Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer--A Plan to Move Forward
Kelloff et al.
Clin. Cancer Res. 2006;12:3661-3697.
ABSTRACT | FULL TEXT  

BRCA1 at the crossroad of multiple cellular pathways: approaches for therapeutic interventions.
Yarden and Papa
Molecular Cancer Therapeutics 2006;5:1396-1404.
ABSTRACT | FULL TEXT  

Endogenous Steroid Hormone Concentrations and Risk of Breast Cancer: Does the Association Vary by a Woman's Predicted Breast Cancer Risk?
Eliassen et al.
JCO 2006;24:1823-1830.
ABSTRACT | FULL TEXT  

Deliberate Deceit of Family Members: A Challenge to Providers of Clinical Genetics Services
Loud et al.
JCO 2006;24:1643-1646.
FULL TEXT  

Spectrum of Mutations in BRCA1, BRCA2, CHEK2, and TP53 in Families at High Risk of Breast Cancer
Walsh et al.
JAMA 2006;295:1379-1388.
ABSTRACT | FULL TEXT  

Cost-effectiveness of preventive strategies for women with a BRCA1 or a BRCA2 mutation.
Anderson et al.
ANN INTERN MED 2006;144:397-406.
ABSTRACT | FULL TEXT  

Assessing BRCA Carrier Probabilities in Extended Families
Barcenas et al.
JCO 2006;24:354-360.
ABSTRACT | FULL TEXT  

The Breast Cancer Susceptibility Gene BRCA1 Regulates Progesterone Receptor Signaling in Mammary Epithelial Cells
Ma et al.
Mol. Endocrinol. 2006;20:14-34.
ABSTRACT | FULL TEXT  

Should women be advised to take prophylactic endocrine treatment outside of a clinical trial setting?
Gogas et al.
Ann Oncol 2005;16:1861-1866.
ABSTRACT | FULL TEXT  

Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement
U.S. Preventive Services Task Force*
ANN INTERN MED 2005;143:355-361.
ABSTRACT | FULL TEXT  

Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review for the U.S. Preventive Services Task Force
Nelson et al.
ANN INTERN MED 2005;143:362-379.
ABSTRACT | FULL TEXT  

BRCA1 in hormonal carcinogenesis: basic and clinical research
Rosen et al.
Endocr Relat Cancer 2005;12:533-548.
ABSTRACT | FULL TEXT  

Ductal Lavage of Fluid-Yielding and Non-Fluid-Yielding Ducts in BRCA1 and BRCA2 Mutation Carriers and Other Women at High Inherited Breast Cancer Risk
Kurian et al.
Cancer Epidemiol. Biomarkers Prev. 2005;14:1082-1089.
ABSTRACT | FULL TEXT  

N-(4-Hydroxyphenyl)retinamide is more potent than other phenylretinamides in inhibiting the growth of BRCA1-mutated breast cancer cells
Simeone et al.
Carcinogenesis 2005;26:1000-1007.
ABSTRACT | FULL TEXT  

Hormonal Interventions: From Adjuvant Therapy to Breast Cancer Prevention
Dunn
aacredbook 2005;2005:185-188.
FULL TEXT  

A Population-Based Study of Bilateral Prophylactic Mastectomy Efficacy in Women at Elevated Risk for Breast Cancer in Community Practices
Geiger et al.
Arch Intern Med 2005;165:516-520.
ABSTRACT | FULL TEXT  

Selective Estrogen-Receptor Modulators for Primary Prevention of Breast Cancer
Fabian and Kimler
JCO 2005;23:1644-1655.
FULL TEXT  

Prevention and Management of Hereditary Breast Cancer
Narod and Offit
JCO 2005;23:1656-1663.
FULL TEXT  

Prevention of Hormone-Related Cancers: Breast Cancer
Dunn et al.
JCO 2005;23:357-367.
ABSTRACT | FULL TEXT  

Utilization of Screening and Preventive Surgery Among Unaffected Carriers of a BRCA1 or BRCA2 Gene Mutation
Wainberg and Husted
Cancer Epidemiol. Biomarkers Prev. 2004;13:1989-1995.
ABSTRACT | FULL TEXT  

Editorial: Preventing Breast, Ovarian Cancer in BRCA Carriers: Rational of Prophylactic Surgery and Promises of Surveillance
Agnantis et al.
Ann. Surg. Oncol. 2004;11:1030-1034.
FULL TEXT  

Identifying and Testing for Hereditary Susceptibility to Common Cancers
Sifri et al.
CA Cancer J Clin 2004;54:309-326.
ABSTRACT | FULL TEXT  

Breast MRI for Women With Hereditary Cancer Risk
Robson and Offit
JAMA 2004;292:1368-1370.
FULL TEXT  

Contralateral Breast Cancer in BRCA1 and BRCA2 Mutation Carriers
Metcalfe et al.
JCO 2004;22:2328-2335.
ABSTRACT | FULL TEXT  

Impact of BRCA1/BRCA2 Counseling and Testing on Newly Diagnosed Breast Cancer Patients
Schwartz et al.
JCO 2004;22:1823-1829.
ABSTRACT | FULL TEXT  

An oncologist-based model of cancer genetic counselling for hereditary breast and ovarian cancer
Contegiacomo et al.
Ann Oncol 2004;15:726-732.
ABSTRACT | FULL TEXT  

Chemoprevention of Cancer
Tsao et al.
CA Cancer J Clin 2004;54:150-180.
ABSTRACT | FULL TEXT  

The Emerging Roles of Screening and Prevention in Women's Cancer
Muggia
The Oncologist 2004;9:228-231.
FULL TEXT  

Bilateral Prophylactic Mastectomy Reduces Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group
Rebbeck et al.
JCO 2004;22:1055-1062.
ABSTRACT | FULL TEXT  

Hormone Replacement Therapy and Life Expectancy After Prophylactic Oophorectomy in Women With BRCA1/2 Mutations: A Decision Analysis
Armstrong et al.
JCO 2004;22:1045-1054.
ABSTRACT | FULL TEXT  

Estrogen Receptor Status in BRCA1- and BRCA2-Related Breast Cancer: The Influence of Age, Grade, and Histological Type
Foulkes et al.
Clin. Cancer Res. 2004;10:2029-2034.
ABSTRACT | FULL TEXT  

Recognition and Management of Hereditary Breast Cancer Syndromes
Thull and Vogel
The Oncologist 2004;9:13-24.
ABSTRACT | FULL TEXT  

The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice
Graziano et al.
Ann Oncol 2003;14:1705-1713.
ABSTRACT | FULL TEXT  

Tamoxifen As Chemoprevention in BRCA1 and BRCA2 Mutation Carriers With Breast Cancer: A Pilot Survey of Physicians
Peshkin et al.
JCO 2003;21:4322-4328.
ABSTRACT | FULL TEXT  

Cancer Genetics in Primary Care
McKelvey and Evans
J. Nutr. 2003;133:3767S-3772.
ABSTRACT | FULL TEXT  

Genetics and the Management of Women at High Risk for Breast Cancer
Mincey
The Oncologist 2003;8:466-473.
ABSTRACT | FULL TEXT  

Frontiers in Cancer Prevention Research
Sabichi et al.
Cancer Res. 2003;63:5649-5655.
FULL TEXT  

The Use of Gene Tests to Detect Hereditary Predisposition to Chronic Disease: Is Cost-Effectiveness Analysis Relevant?
Col
Med Decis Making 2003;23:441-448.
ABSTRACT  

Breast Cancer After Hodgkin Disease: Hope for a Safer Cure
Yahalom
JAMA 2003;290:529-531.
FULL TEXT  

Breast and Ovarian Cancer
Wooster and Weber
NEJM 2003;348:2339-2347.
FULL TEXT  

Genes, Hormones, and Pathways to Breast Cancer
Hartge
NEJM 2003;348:2352-2354.
FULL TEXT  

Use of Genetic Testing and Prophylactic Mastectomy and Oophorectomy in Women With Breast or Ovarian Cancer From Families With a BRCA1 or BRCA2 Mutation
Meijers-Heijboer et al.
JCO 2003;21:1675-1681.
ABSTRACT | FULL TEXT  

Re: Tamoxifen May Be an Effective Treatment for BRCA1-Related Breast Cancer Irrespective of Estrogen Receptor Status
Cappelletti et al.
JNCI J Natl Cancer Inst 2003;95:629-630.
FULL TEXT  

Selective Estrogen-Receptor Modulators -- Mechanisms of Action and Application to Clinical Practice
Riggs and Hartmann
NEJM 2003;348:618-629.
FULL TEXT  

Evidence-based management options for women at increased breast/ovarian cancer risk
Pichert et al.
Ann Oncol 2003;14:9-19.
ABSTRACT | FULL TEXT  

High Prevalence of Premalignant Lesions in Prophylactically Removed Breasts From Women at Hereditary Risk for Breast Cancer
Hoogerbrugge et al.
JCO 2003;21:41-45.
ABSTRACT | FULL TEXT  

National Surgical Adjuvant Breast and Bowel Project Update: Prevention Trials and Endocrine Therapy of Ductal Carcinoma in Situ
Vogel et al.
Clin. Cancer Res. 2003;9:495S-501S.
ABSTRACT | FULL TEXT  

Tamoxifen May Be an Effective Adjuvant Treatment for BRCA1-Related Breast Cancer Irrespective of Estrogen Receptor Status
Foulkes et al.
JNCI J Natl Cancer Inst 2002;94:1504-1506.
FULL TEXT  

Utilization of Breast Cancer Screening in a Clinically Based Sample of Women after BRCA1/2 Testing
Peshkin et al.
Cancer Epidemiol. Biomarkers Prev. 2002;11:1115-1118.
ABSTRACT | FULL TEXT  

Oophorectomy in Carriers of BRCA Mutations
Zhuang et al.
NEJM 2002;347:1037-1040.
FULL TEXT  

Cancer Prevention Science and Practice
Lippman and Hong
Cancer Res. 2002;62:5119-5125.
FULL TEXT  

Estrogen Receptor-Beta Expression in Hereditary Breast Cancer
Daidone et al.
JCO 2002;20:3752-3753.
FULL TEXT  

American Society of Clinical Oncology Technology Assessment of Pharmacologic Interventions for Breast Cancer Risk Reduction Including Tamoxifen, Raloxifene, and Aromatase Inhibition
Chlebowski et al.
JCO 2002;20:3328-3343.
ABSTRACT | FULL TEXT  

Chemoprevention of Breast Cancer: A Summary of the Evidence for the U.S. Preventive Services Task Force
Kinsinger et al.
ANN INTERN MED 2002;137:59-69.
ABSTRACT | FULL TEXT  

Risk-Reducing Salpingo-oophorectomy in Women with a BRCA1 or BRCA2 Mutation
Kauff et al.
NEJM 2002;346:1609-1615.
ABSTRACT | FULL TEXT  

Prophylactic Oophorectomy to Reduce the Risk of Ovarian and Breast Cancer in Carriers of BRCA Mutations
Haber
NEJM 2002;346:1660-1662.
FULL TEXT  

Effect of Prevention Strategies on Survival and Quality-Adjusted Survival of Women With BRCA1/2 Mutations: An Updated Decision Analysis
Grann et al.
JCO 2002;20:2520-2529.
ABSTRACT | FULL TEXT  

Breast Cancer Prevention
Love
The Oncologist 2002;7:100-102.
FULL TEXT  

Recent developments: Breast cancer
Morrow and Gradishar
BMJ 2002;324:410-414.
FULL TEXT  

Cancer Prevention by Delay : Commentary re: J. A. O'Shaughnessy et al., Treatment and Prevention of Intraepithelial Neoplasia: An Important Target for Accelerated New Agent Development. Clin. Cancer Res., 8: 314-346, 2002.
Lippman and Ki Hong
Clin. Cancer Res. 2002;8:305-313.
FULL TEXT  

Beyond Tamoxifen: New Endpoints for Breast Cancer Chemoprevention, New Drugs for Breast Cancer Prevention
FABIAN and KIMLER
Ann. N. Y. Acad. Sci. 2001;952:44-59.
ABSTRACT | FULL TEXT  

Genetics Moves Into the Medical Mainstream
Collins and Guttmacher
JAMA 2001;286:2322-2324.
FULL TEXT