© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 18, 1365-1372,
September 18, 2002
© 2002 Oxford University Press
ARTICLE |
Cancer Risk Estimates for BRCA1 Mutation Carriers Identified in a Risk Evaluation Program
Affiliations of authors: M. S. Brose, B. L. Weber (Department of Medicine and Abramson Family Cancer Research Institute), K. A. Calzone, J. E. Stopfer, K. L. Nathanson (Department of Medicine), University of Pennsylvania Cancer Center, Philadelphia; T. R. Rebbeck, Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia.
Correspondence to: Barbara Weber, M.D., Abramson Family Cancer Research Institute at The University of Pennsylvania Cancer Center, BRB II/II, Rm. 514, 421 Curie Blvd., Philadelphia, PA 19104 (e-mail: weberb{at}mail.med.upenn.edu).
Background: Increasing numbers of BRCA1 mutation carriers are being identified in cancer risk evaluation programs. However, no estimates of cancer risk specific to a clinic-based population of mutation carriers are available. These data are clinically relevant, because estimates based on families ascertained for linkage studies may overestimate cancer risk in mutation carriers, and population-based series may underestimate it. Wide variation in risk estimates from these disparate ascertainment groups makes counseling in risk evaluation programs difficult. The purpose of this study was to estimate BRCA1-related cancer risks for individuals ascertained in a breast cancer risk evaluation clinic. Methods: Cumulative observed and age-adjusted cancer risk estimates were determined by analyzing 483 BRCA1 mutation carriers in 147 families identified in two academic breast and ovarian cancer risk evaluation clinics. Cancer risks were computed from the proportion of individuals diagnosed with cancer during a 10-year age interval from among the total number of individuals alive and cancer-free at the beginning of that interval. Age-of-diagnosis comparisons were made using two-sided Student's t tests. Results: By age 70, female breast cancer risk was 72.8% (95% confidence interval [CI] = 67.9% to 77.7%) and ovarian cancer risk was 40.7% (95% CI = 35.7% to 45.6%). The risk for a second primary breast cancer by age 70 was 40.5% (95% CI = 34.1% to 47.0%). We also identified an increased risk of cancer of the colon (twofold), pancreas (threefold), stomach (fourfold), and fallopian tube (120-fold) in BRCA1 mutation carriers as compared with Surveillance, Epidemiology, and End Results (SEER) Program population-based estimates. Conclusion: The estimates for breast and ovarian cancer risk in BRCA1 mutation carriers is higher than population-based estimates but lower than estimates based on families ascertained for linkage studies. These cancer risk estimates may most closely approximate those faced by BRCA1 mutation carriers identified in risk evaluation clinics.
This article has been cited by other articles:
![]() |
M. Fatouros, G. Baltoyiannis, and D. H. Roukos The Predominant Role of Surgery in the Prevention and New Trends in the Surgical Treatment of Women With BRCA1/2 Mutations Ann. Surg. Oncol., January 1, 2008; 15(1): 21 - 33. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. C. Tai, S. Domchek, G. Parmigiani, and S. Chen Breast Cancer Risk Among Male BRCA1 and BRCA2 Mutation Carriers J Natl Cancer Inst, December 5, 2007; 99(23): 1811 - 1814. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. H. Vaz, P. M. Machado, R. D. Brandao, C. T. Laranjeira, J. S. Eugenio, A. H. Fernandes, and S. P. Andre Familial Breast/Ovarian Cancer and BRCA1/2 Genetic Screening: The Role of Immunohistochemistry as an Additional Method in the Selection of Patients J. Histochem. Cytochem., November 1, 2007; 55(11): 1105 - 1113. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. E Brand, M. M Lerch, W. S Rubinstein, J. P Neoptolemos, D. C Whitcomb, R. H Hruban, T. A Brentnall, H. T Lynch, M. I Canto, and Participants of the Fourth International Symposium Advances in counselling and surveillance of patients at risk for pancreatic cancer Gut, October 1, 2007; 56(10): 1460 - 1469. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. R. Bradbury, J. J. Dignam, C. N. Ibe, S. L. Auh, F. J. Hlubocky, S. A. Cummings, M. White, O. I. Olopade, and C. K. Daugherty How Often Do BRCA Mutation Carriers Tell Their Young Children of the Family's Risk for Cancer? A Study of Parental Disclosure of BRCA Mutations to Minors and Young Adults J. Clin. Oncol., August 20, 2007; 25(24): 3705 - 3711. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Y. Karlan, A. Berchuck, and D. Mutch The Role of Genetic Testing for Cancer Susceptibility in Gynecologic Practice Obstet. Gynecol., July 1, 2007; 110(1): 155 - 167. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Douglas, A. M. Levin, K. A. Zuhlke, A. M. Ray, G. R. Johnson, E. M. Lange, D. P. Wood, and K. A. Cooney Common Variation in the BRCA1 Gene and Prostate Cancer Risk Cancer Epidemiol. Biomarkers Prev., July 1, 2007; 16(7): 1510 - 1516. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Kadouri, A. Hubert, Y. Rotenberg, T. Hamburger, M. Sagi, C. Nechushtan, D. Abeliovich, and T. Peretz Cancer risks in carriers of the BRCA1/2 Ashkenazi founder mutations J. Med. Genet., July 1, 2007; 44(7): 467 - 471. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Offit BRCA Mutation Frequency and Penetrance: New Data, Old Debate J Natl Cancer Inst, December 6, 2006; 98(23): 1675 - 1677. [Full Text] [PDF] |
||||
![]() |
J Ji and K Hemminki Second gastric cancers among patients with primary sporadic and familial cancers in Sweden. Gut, June 1, 2006; 55(6): 896 - 898. [Full Text] [PDF] |
||||
![]() |
H. Grabsch, M. Dattani, L. Barker, N. Maughan, K. Maude, O. Hansen, H. E. Gabbert, P. Quirke, and W. Mueller Expression of DNA Double-Strand Break Repair Proteins ATM and BRCA1 Predicts Survival in Colorectal Cancer Clin. Cancer Res., March 1, 2006; 12(5): 1494 - 1500. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. H. Barcenas, G.M. M. Hosain, B. Arun, J. Zong, X. Zhou, J. Chen, J. M. Cortada, G. B. Mills, G. E. Tomlinson, A. R. Miller, et al. Assessing BRCA Carrier Probabilities in Extended Families J. Clin. Oncol., January 20, 2006; 24(3): 354 - 360. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Armstrong, B. Weber, P. A. Ubel, N. Peters, J. Holmes, and J. S. Schwartz Individualized Survival Curves Improve Satisfaction With Cancer Risk Management Decisions in Women With BRCA1/2 Mutations J. Clin. Oncol., December 20, 2005; 23(36): 9319 - 9328. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. L. Kramer, I. A. Velazquez, B. E. Chen, P. S. Rosenberg, J. P. Struewing, and M. H. Greene Prophylactic Oophorectomy Reduces Breast Cancer Penetrance During Prospective, Long-Term Follow-Up of BRCA1 Mutation Carriers J. Clin. Oncol., December 1, 2005; 23(34): 8629 - 8635. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Cass, C. Holschneider, N. Datta, D. Barbuto, A. E. Walts, and B. Y. Karlan BRCA-Mutation-Associated Fallopian Tube Carcinoma: A Distinct Clinical Phenotype? Obstet. Gynecol., December 1, 2005; 106(6): 1327 - 1334. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. R. Rebbeck, T. Friebel, T. Wagner, H. T. Lynch, J. E. Garber, M. B. Daly, C. Isaacs, O. I. Olopade, S. L. Neuhausen, L. van 't Veer, et al. Effect of Short-Term Hormone Replacement Therapy on Breast Cancer Risk Reduction After Bilateral Prophylactic Oophorectomy in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group J. Clin. Oncol., November 1, 2005; 23(31): 7804 - 7810. [Abstract] [Full Text] [PDF] |
||||
![]() |
U.S. Preventive Services Task Force* Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement Ann Intern Med, September 6, 2005; 143(5): 355 - 361. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. D. Nelson, L. H. Huffman, R. Fu, and E. L. Harris Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review for the U.S. Preventive Services Task Force Ann Intern Med, September 6, 2005; 143(5): 362 - 379. [Abstract] [Full Text] [PDF] |
||||
![]() |
C J van Asperen, R M Brohet, E J Meijers-Heijboer, N Hoogerbrugge, S Verhoef, H F A Vasen, M G E M Ausems, F H Menko, E B Gomez Garcia, J G M Klijn, et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary J. Med. Genet., September 1, 2005; 42(9): 711 - 719. [Abstract] [Full Text] [PDF] |
||||
![]() |
A.-M. Simeone, C.-X. Deng, G. J. Kelloff, V. E. Steele, M. M. Johnson, and A. M. Tari N-(4-Hydroxyphenyl)retinamide is more potent than other phenylretinamides in inhibiting the growth of BRCA1-mutated breast cancer cells Carcinogenesis, May 1, 2005; 26(5): 1000 - 1007. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. J. Fabian and B. F. Kimler Selective Estrogen-Receptor Modulators for Primary Prevention of Breast Cancer J. Clin. Oncol., March 10, 2005; 23(8): 1644 - 1655. [Full Text] [PDF] |
||||
![]() |
B Leegte, A H van der Hout, A M Deffenbaugh, M K Bakker, I M Mulder, A ten Berge, E P Leenders, J Wesseling, J de Hullu, N Hoogerbrugge, et al. Phenotypic expression of double heterozygosity for BRCA1 and BRCA2 germline mutations J. Med. Genet., March 1, 2005; 42(3): e20 - e20. [Full Text] [PDF] |
||||
![]() |
M. M. Bertagnolli Surgical Prevention of Cancer J. Clin. Oncol., January 10, 2005; 23(2): 324 - 332. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Lorenzo Bermejo and K. Hemminki Risk of cancer at sites other than the breast in Swedish families eligible for BRCA1 or BRCA2 mutation testing Ann. Onc., December 1, 2004; 15(12): 1834 - 1841. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. J. Agnantis, E. Paraskevaidis, and D. Roukos Editorial: Preventing Breast, Ovarian Cancer in BRCA Carriers: Rational of Prophylactic Surgery and Promises of Surveillance Ann. Surg. Oncol., December 1, 2004; 11(12): 1030 - 1034. [Full Text] [PDF] |
||||
![]() |
T. Kirchhoff, N. D. Kauff, N. Mitra, K. Nafa, H. Huang, C. Palmer, T. Gulati, E. Wadsworth, S. Donat, M. E. Robson, et al. BRCA Mutations and Risk of Prostate Cancer in Ashkenazi Jews Clin. Cancer Res., May 1, 2004; 10(9): 2918 - 2921. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. R. Rebbeck, T. Friebel, H. T. Lynch, S. L. Neuhausen, L. van 't Veer, J. E. Garber, G. R. Evans, S. A. Narod, C. Isaacs, E. Matloff, et al. Bilateral Prophylactic Mastectomy Reduces Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group J. Clin. Oncol., March 15, 2004; 22(6): 1055 - 1062. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Liede, B. Y. Karlan, and S. A. Narod Cancer Risks for Male Carriers of Germline Mutations in BRCA1 or BRCA2: A Review of the Literature J. Clin. Oncol., February 15, 2004; 22(4): 735 - 742. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. E. Garber and S. Syngal One Less Thing to Worry About: The Shrinking Spectrum of Tumors in BRCA Founder Mutation Carriers J Natl Cancer Inst, January 7, 2004; 96(1): 2 - 3. [Full Text] [PDF] |
||||
![]() |
B. L. Niell, G. Rennert, J. D. Bonner, R. Almog, L. P. Tomsho, and S. B. Gruber BRCA1 and BRCA2 Founder Mutations and the Risk of Colorectal Cancer J Natl Cancer Inst, January 7, 2004; 96(1): 15 - 21. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Kirchhoff, J. M. Satagopan, N. D. Kauff, H. Huang, P. Kolachana, C. Palmer, H. Rapaport, K. Nafa, N. A. Ellis, and K. Offit Frequency of BRCA1 and BRCA2 Mutations in Unselected Ashkenazi Jewish Patients With Colorectal Cancer J Natl Cancer Inst, January 7, 2004; 96(1): 68 - 70. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. N. Peshkin, C. Isaacs, C. Finch, S. Kent, and M. D. Schwartz Tamoxifen As Chemoprevention in BRCA1 and BRCA2 Mutation Carriers With Breast Cancer: A Pilot Survey of Physicians J. Clin. Oncol., December 1, 2003; 21(23): 4322 - 4328. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. A. Levine, P. A. Argenta, C. J. Yee, D. S. Marshall, N. Olvera, F. Bogomolniy, J. A. Rahaman, M. E. Robson, K. Offit, R. R. Barakat, et al. Fallopian Tube and Primary Peritoneal Carcinomas Associated With BRCA Mutations J. Clin. Oncol., November 15, 2003; 21(22): 4222 - 4227. [Abstract] [Full Text] [PDF] |
||||
![]() |
M.-C. King, J. H. Marks, and J. B. Mandell Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2 Science, October 24, 2003; 302(5645): 643 - 646. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. A. Dragani 10 Years of Mouse Cancer Modifier Loci: Human Relevance Cancer Res., June 15, 2003; 63(12): 3011 - 3018. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Wooster and B. L. Weber Breast and Ovarian Cancer N. Engl. J. Med., June 5, 2003; 348(23): 2339 - 2347. [Full Text] [PDF] |
||||
![]() |
H. A. Risch and S. A. Narod Re: Cancer Risks in BRCA1 Carriers: Time for the Next Generation of Studies J Natl Cancer Inst, May 21, 2003; 95(10): 758 - 758. [Full Text] [PDF] |
||||
![]() |
A-M Martin, P A Kanetsky, B Amirimani, T A Colligon, G Athanasiadis, H A Shih, M R Gerrero, K Calzone, T R Rebbeck, and B L Weber Germline TP53 mutations in breast cancer families with multiple primary cancers: is TP53 a modifier of BRCA1? J. Med. Genet., April 1, 2003; 40(4): e34 - 34. [Full Text] [PDF] |
||||
![]() |
S. M. Domchek, A. Eisen, K. Calzone, J. Stopfer, A. Blackwood, and B. L. Weber Application of Breast Cancer Risk Prediction Models in Clinical Practice J. Clin. Oncol., February 15, 2003; 21(4): 593 - 601. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. H. Roukos, N. J. Agnanti, E. Paraskevaidis, and A. M. Kappas Approaching the Dilemma Between Prophylactic Bilateral Mastectomy or Oophorectomy for Breast and Ovarian Cancer Prevention in Carriers of BRCA1 or BRCA2 Mutations Ann. Surg. Oncol., December 1, 2002; 9(10): 941 - 943. [Full Text] [PDF] |
||||
![]() |
Improved Assessment of Cancer Risks in BRCA1 Mutation Carriers Journal Watch Women's Health, October 9, 2002; 2002(1009): 1 - 1. [Full Text] |
||||
![]() |
S. B. Gruber and G. M. Petersen Cancer Risks in BRCA1 Carriers: Time for the Next Generation of Studies J Natl Cancer Inst, September 18, 2002; 94(18): 1344 - 1345. [Full Text] [PDF] |
||||















