© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 227-238, Copyright © 1997 by Oxford University Press
DA Berry, G Parmigiani, J Sanchez, J Schildkraut and E Winer
BACKGROUND: Heritable mutations of the breast cancer gene BRCA1 are rare,
occurring in fewer than 1% of women in the general population, and
therefore account for a small proportion of cases of breast and ovarian
cancers. Nevertheless, the presence of such mutations is highly predictive
of the development of these cancers. PURPOSE: We developed and applied a
mathematic model for calculating the probability that a woman with a family
history of breast and/or ovarian cancer carries a mutation of BRCA1.
METHODS AND RESULTS: As a basis for the model, we use Mendelian genetics
and apply Bayes' theorem to information on the family history of these
diseases. Of importance are the exact relationships of all family members,
including both affected and unaffected members, and ages at diagnosis of
the affected members and current ages of the unaffected members. We used
available estimates of BRCA1 mutation frequencies in the general population
and age-specific incidence rates of breast and ovarian cancers in carriers
and noncarriers of mutations to estimate the probability that a particular
member of the family carries a mutation. This probability is based on
cancer statuses of all first- and second-degree relatives. We first
describe the model by considering single individuals: a woman diagnosed
with breast and/or ovarian cancer and also a woman free of cancer. We next
considered two artificial and two actual family histories and addressed the
sensitivity of our calculations to various assumptions. Particular
relationships of family members with and without cancer can have a
substantial impact on the probability of carrying a susceptibility gene.
Ages at diagnosis of affected family members and their types of cancer are
also important. A woman with two primary cancers can have a probability of
carrying a mutation in excess of 80%, even with no other information about
family history. The number and relationships of unaffected members, along
with their current ages or ages at death, are critical determinants of
one's carrier probability. An affected woman with several cancers in her
family can have a probability of carrying a mutation that ranges from close
to 100% to less than 5%. CONCLUSION: Our model gives informative and
specific probabilities that a particular woman carries a mutation.
IMPLICATIONS: This model focuses on mutations in BRCA1 and assumes that all
other breast cancer is sporadic. With the cloning of BRCA2, we now know
that this assumption is incorrect. We have adjusted the model to include
BRCA2, but the use of this version must await publication of penetrance
data for BRCA2, including those for male breast cancer that are apparently
associated with BRCA2 but not with BRCA1. The current model is,
nevertheless, appropriate and useful. Of principal importance is its
potential and that of improved versions for aiding women and their health
care providers in assessing the need for genetic testing.
ARTICLES
Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on family history
Institute of Statistics and Decision Sciences, Duke University, Durham, NC 27708-0251, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. M. Euhus, D. Bu, S. Milchgrub, X.-J. Xie, A. Bian, A. M. Leitch, and C. M. Lewis DNA Methylation in Benign Breast Epithelium in Relation to Age and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1051 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yu, A. Park, E. Morris, L. Liberman, P. I. Borgen, and T. A. King MRI Screening in a Clinic Population with a Family History of Breast Cancer Ann. Surg. Oncol., February 1, 2008; 15(2): 452 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Gao, X.-J. Xie, C. Huang, D. S. Shames, T. T-L. Chen, C. M. Lewis, A. Bian, B. Zhang, O. I. Olopade, J. E. Garber, et al. RASSF1A Polymorphism A133S Is Associated with Early Onset Breast Cancer in BRCA1/2 Mutation Carriers Cancer Res., January 1, 2008; 68(1): 22 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Balmana, E. W. Steyerberg, and S. Syngal Risk Quantification for Carrying Mutations in Lynch Syndrome Genes ASCO Educational Book, January 1, 2008; 2008(1): 59 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Vogel, D. P. Atchley, J. Erlichman, K. R. Broglio, K. J. Ready, V. Valero, C. I. Amos, G. N. Hortobagyi, K. H. Lu, and B. Arun BRCA1 and BRCA2 Genetic Testing in Hispanic Patients: Mutation Prevalence and Evaluation of the BRCAPRO Risk Assessment Model J. Clin. Oncol., October 10, 2007; 25(29): 4635 - 4641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Parmigiani, S. Chen, E. S. Iversen Jr, T. M. Friebel, D. M. Finkelstein, H. Anton-Culver, A. Ziogas, B. L. Weber, A. Eisen, K. E. Malone, et al. Validity of Models for Predicting BRCA1 and BRCA2 Mutations Ann Intern Med, October 2, 2007; 147(7): 441 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Euhus, D. Bu, R. Ashfaq, X.-J. Xie, A. Bian, A. M. Leitch, and C. M. Lewis Atypia and DNA Methylation in Nipple Duct Lavage in Relation to Predicted Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., September 1, 2007; 16(9): 1812 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Parmigiani and D. A. Berry In Reply J. Clin. Oncol., June 20, 2007; 25(18): 2634 - 2635. [Full Text] [PDF]
|
|
|
|
|
|
W. Wang, S. Chen, K. A. Brune, R. H. Hruban, G. Parmigiani, and A. P. Klein PancPRO: Risk Assessment for Individuals With a Family History of Pancreatic Cancer J. Clin. Oncol., April 10, 2007; 25(11): 1417 - 1422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Saslow, C. Boetes, W. Burke, S. Harms, M. O. Leach, C. D. Lehman, E. Morris, E. Pisano, M. Schnall, S. Sener, et al. American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography CA Cancer J Clin, March 1, 2007; 57(2): 75 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Simard, M. Dumont, A.-M. Moisan, V. Gaborieau, H. Vezina, F. Durocher, J. Chiquette, M. Plante, D. Avard, P. Bessette, et al. Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer J. Med. Genet., February 1, 2007; 44(2): 107 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. James, J. E. Quinn, P. B. Mullan, P. G. Johnston, and D. P. Harkin BRCA1, a Potential Predictive Biomarker in the Treatment of Breast Cancer Oncologist, February 1, 2007; 12(2): 142 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chen, W. Wang, S. Lee, K. Nafa, J. Lee, K. Romans, P. Watson, S. B. Gruber, D. Euhus, K. W. Kinzler, et al. Prediction of germline mutations and cancer risk in the Lynch syndrome. JAMA, September 27, 2006; 296(12): 1479 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. James, R. Doherty, M. Harris, B. N. Mukesh, A. Milner, M.-A. Young, and C. Scott Optimal Selection of Individuals for BRCA Mutation Testing: A Comparison of Available Methods J. Clin. Oncol., February 1, 2006; 24(4): 707 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nanda, L. P. Schumm, S. Cummings, J. D. Fackenthal, L. Sveen, F. Ademuyiwa, M. Cobleigh, L. Esserman, N. M. Lindor, S. L. Neuhausen, et al. Genetic Testing in an Ethnically Diverse Cohort of High-Risk Women: A Comparative Analysis of BRCA1 and BRCA2 Mutations in American Families of European and African Ancestry JAMA, October 19, 2005; 294(15): 1925 - 1933. [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]
|
|
|
|
|
|
A. W. Kurian, M. A. Mills, M. Jaffee, B. M. Sigal, N. M. Chun, K. E. Kingham, L. C. Collins, K. W. Nowels, S. K. Plevritis, J. E. Garber, et al. 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 Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1082 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Brewer, J. Ranger-Moore, A. Baruche, D. S. Alberts, M. Greene, D. Thompson, Y. Liu, J. Davis, and P. H. Bartels Exploratory Study of Ovarian Intraepithelial Neoplasia Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 299 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Lewis, L. R. Cler, D.-W. Bu, S. Zochbauer-Muller, S. Milchgrub, E. Z. Naftalis, A. M. Leitch, J. D. Minna, and D. M. Euhus Promoter Hypermethylation in Benign Breast Epithelium in Relation to Predicted Breast Cancer Risk Clin. Cancer Res., January 1, 2005; 11(1): 166 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Green, S. K. Peterson, M. W. Baker, G. R. Harper, L. C. Friedman, W. S. Rubinstein, and D. T. Mauger Effect of a Computer-Based Decision Aid on Knowledge, Perceptions, and Intentions About Genetic Testing for Breast Cancer Susceptibility: A Randomized Controlled Trial JAMA, July 28, 2004; 292(4): 442 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F Marroni, P Aretini, E D'Andrea, M A Caligo, L Cortesi, A Viel, E Ricevuto, M Montagna, G Cipollini, S Ferrari, et al. Evaluation of widely used models for predicting BRCA1 and BRCA2 mutations J. Med. Genet., April 1, 2004; 41(4): 278 - 285. [Full Text] [PDF]
|
|
|
|
|
|
H Hampel, K Sweet, J A Westman, K Offit, and C Eng Referral for cancer genetics consultation: a review and compilation of risk assessment criteria J. Med. Genet., February 1, 2004; 41(2): 81 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Mincey Genetics and the Management of Women at High Risk for Breast Cancer Oncologist, October 1, 2003; 8(5): 466 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Smith, D. Saslow, K. Andrews Sawyer, W. Burke, M. E. Costanza, W. P. Evans III, R. S. Foster Jr., E. Hendrick, H. J. Eyre, and S. Sener American Cancer Society Guidelines for Breast Cancer Screening: Update 2003 CA Cancer J Clin, May 1, 2003; 53(3): 141 - 169. [Abstract] [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]
|
|
|
|
|
|
M. A. Brewer, K. Johnson, M. Follen, D. Gershenson, and R. Bast Jr. Prevention of Ovarian Cancer: Intraepithelial Neoplasia Clin. Cancer Res., January 1, 2003; 9(1): 20 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Metcalfe and S. A. Narod Breast Cancer Risk Perception Among Women Who Have Undergone Prophylactic Bilateral Mastectomy J Natl Cancer Inst, October 16, 2002; 94(20): 1564 - 1569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N D Kauff, P Perez-Segura, M E Robson, L Scheuer, B Siegel, A Schluger, B Rapaport, T S Frank, K Nafa, N A Ellis, et al. Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families J. Med. Genet., August 1, 2002; 39(8): 611 - 614. [Full Text] [PDF]
|
|
|
|
|
|
D. M. Euhus, K. C. Smith, L. Robinson, A. Stucky, O. I. Olopade, S. Cummings, J. E. Garber, A. Chittenden, G. B. Mills, P. Rieger, et al. Pretest Prediction of BRCA1 or BRCA2 Mutation by Risk Counselors and the Computer Model BRCAPRO J Natl Cancer Inst, June 5, 2002; 94(11): 844 - 851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Euhus, L. Cler, N. Shivapurkar, S. Milchgrub, G. N. Peters, A. M. Leitch, S. Heda, and A. F. Gazdar Loss of Heterozygosity in Benign Breast Epithelium in Relation to Breast Cancer Risk J Natl Cancer Inst, June 5, 2002; 94(11): 858 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Berry, E. S. Iversen Jr, D. F. Gudbjartsson, E. H. Hiller, J. E. Garber, B. N. Peshkin, C. Lerman, P. Watson, H. T. Lynch, S. G. Hilsenbeck, et al. BRCAPRO Validation, Sensitivity of Genetic Testing of BRCA1/BRCA2, and Prevalence of Other Breast Cancer Susceptibility Genes J. Clin. Oncol., June 1, 2002; 20(11): 2701 - 2712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Berry Role of Population-Based Studies in Assessing Genetic Cancer Risk J Natl Cancer Inst, August 15, 2001; 93(16): 1188 - 1189. [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Dunson Commentary: Practical Advantages of Bayesian Analysis of Epidemiologic Data Am. J. Epidemiol., June 15, 2001; 153(12): 1222 - 1226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Gail and J. P. Costantino Validating and Improving Models for Projecting the Absolute Risk of Breast Cancer J Natl Cancer Inst, March 7, 2001; 93(5): 334 - 335. [Full Text] [PDF]
|
|
|
|
 |
|
 E. B Claus Risk models in genetic epidemiology Statistical Methods in Medical Research, December 1, 2000; 9(6): 589 - 601. [Abstract] [PDF]
|
|
|
|
|
|
R. T. Penson, M. V. Seiden, K. M. Shannon, M. L. Lubratovich, M. Roche, B. A. Chabner, and T. J. Lynch Jr. Communicating Genetic Risk: Pros, Cons, and Counsel Oncologist, April 1, 2000; 5(2): 152 - 161. [Abstract] [Full Text]
|
|
|
|
|
|
M. H. Gail, J. P. Costantino, J. Bryant, R. Croyle, L. Freedman, K. Helzlsouer, and V. Vogel Weighing the Risks and Benefits of Tamoxifen Treatment for Preventing Breast Cancer J Natl Cancer Inst, November 3, 1999; 91(21): 1829 - 1846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hernandez and B. M. Evers Functional Genomics: Clinical Effect and the Evolving Role of the Surgeon Arch Surg, November 1, 1999; 134(11): 1209 - 1215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. Bluman, B. K. Rimer, D. A. Berry, N. Borstelmann, J. D. Iglehart, K. Regan, J. Schildkraut, and E. P. Winer Attitudes, Knowledge, and Risk Perceptions of Women With Breast and/or Ovarian Cancer Considering Testing for BRCA1 and BRCA2 J. Clin. Oncol., March 1, 1999; 17(3): 1040 - 1040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Hartmann, D. J. Schaid, J. E. Woods, T. P. Crotty, J. L. Myers, P.G. Arnold, P. M. Petty, T. A. Sellers, J. L. Johnson, S. K. McDonnell, et al. Efficacy of Bilateral Prophylactic Mastectomy in Women with a Family History of Breast Cancer N. Engl. J. Med., January 14, 1999; 340(2): 77 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. T. Croyle and C. Lerman Risk Communication in Genetic Testing for Cancer Susceptibility J Natl Cancer Inst Monographs, January 1, 1999; 1999(25): 59 - 66. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. O. Tengs, E. P. Winer, S. Paddock, O. Aguilar-Chavez, and D. A. Berry Testing for the BRCA1 and BRCA2 Breast-Ovarian Cancer Susceptibility Genes: A Decision Analysis Med Decis Making, October 1, 1998; 18(4): 365 - 375. [Abstract] [PDF]
|
|
|
|
|
|
F. J. Couch and L. C. Hartmann BRCA1 Testing--Advances and Retreats JAMA, March 25, 1998; 279(12): 955 - 957. [Full Text] [PDF]
|
|
|
|
|
|
F. J. Couch, M. L. DeShano, M. A. Blackwood, K. Calzone, J. Stopfer, L. Campeau, A. Ganguly, T. Rebbeck, B. L. Weber, L. Jablon, et al. BRCA1 Mutations in Women Attending Clinics That Evaluate the Risk of Breast Cancer N. Engl. J. Med., May 15, 1997; 336(20): 1409 - 1415. [Abstract] [Full Text] [PDF]
|
|