Screen-positive rates and agreement among six family history screening protocols for breast/ovarian cancer in a population-based cohort of 21- to 55-year-old women

Purpose: Mutations in the BRCA1 and BRCA2 genes are responsible for approximately 2% of breast cancers by age 70 years. Professional and governmental groups recommend using family history protocols as an initial step in identifying women and families for mutation testing. We assess screen-positive rates and levels of agreement between these protocols.Methods: We applied six family history screening protocols to a population-based cohort of 321 women, age 21 to 55 years, who reported their personal and family history of breast and ovarian cancer.Results: The proportion of women and families identified as candidates for mutation testing ranged from 4.4% to 7.8%, depending on the protocol. The protocols had low or fair agreement (kappa <0.75 for 14 of 15 comparisons), but all identified six women (1.9%, 95% confidence interval 0.7%–4.0%) as screen positive. When the effect of missing ages of cancer onset was modeled, these rates increased (range 6.5%–11.5%), and nine women (2.8%) were screen positive by all protocols.Conclusion: Given limitations of family history as a screening test for hereditary cancer related to BRCA1/2 mutations, 1% to 2% of women in the general population should initially be identified for mutation testing. One way to achieve this would be to require that multiple screening protocols agree.

[1]  U. P. S. T. Force.  Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement , 2005, Annals of Internal Medicine.

[2]  Rongwei Fu,et al.  Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review for the U.S. Preventive Services Task Force , 2005, Annals of Internal Medicine.

[3]  D. Easton,et al.  The BOADICEA model of genetic susceptibility to breast and ovarian cancer , 2004, British Journal of Cancer.

[4]  N. Rahman,et al.  A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO , 2004, Journal of Medical Genetics.

[5]  K. Offit,et al.  Referral for cancer genetics consultation: a review and compilation of risk assessment criteria , 2004, Journal of Medical Genetics.

[6]  B. Weber,et al.  Application of breast cancer risk prediction models in clinical practice. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  J. Garber,et al.  A population-based study of Ashkenazi Jewish women’s attitudes toward genetic discrimination and BRCA1/2 testing , 2002, Genetics in Medicine.

[8]  R. Eeles,et al.  Genetic testing for women previously diagnosed with breast/ovarian cancer: examining the impact of BRCA1 and BRCA2 mutation searching. , 2002, Genetic testing.

[9]  S. Coughlin,et al.  Population-Based Estimates of the Prevalence of Family History of Cancer among Women , 2002, Public Health Genomics.

[10]  G. Elwyn,et al.  Reactions of GPs to a triage-controlled referral system for cancer genetics. , 2002, Family practice.

[11]  C. Isaacs,et al.  Impact of BRCA1/BRCA2 mutation testing on psychologic distress in a clinic-based sample. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  Å. Borg,et al.  Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer. , 2001, Journal of the National Cancer Institute.

[13]  N. Carson,et al.  A preliminary validation of a family history assessment form to select women at risk for breast or ovarian cancer for referral to a genetics center , 2000, Clinical genetics.

[14]  E. Ostrander,et al.  Frequency of BRCA1/BRCA2 mutations in a population‐based sample of young breast carcinoma cases , 2000, Cancer.

[15]  G. Giles,et al.  Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[16]  Nazneen,et al.  Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. , 1999, Journal of the National Cancer Institute.

[17]  M. Cho,et al.  Commercialization of BRCA1/2 testing: practitioner awareness and use of a new genetic test. , 1999, American journal of medical genetics.

[18]  S. Cummings,et al.  Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  S. Narod,et al.  What you don't know can hurt you: adverse psychologic effects in members of BRCA1-linked and BRCA2-linked families who decline genetic testing. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  K Offit,et al.  BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing. , 1997, JAMA.

[21]  P. Tonin,et al.  A descriptive study of BRCA1 testing and reactions to disclosure of test results , 1997, Cancer.

[22]  F. Couch,et al.  BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. , 1997, The New England journal of medicine.

[23]  J. Benkendorf,et al.  Controlled trial of pretest education approaches to enhance informed decision-making for BRCA1 gene testing. , 1997, Journal of the National Cancer Institute.

[24]  P. Devilee,et al.  Males at–risk for the BRCA1‐1ene, the psychological impact , 1996 .

[25]  B. Trock,et al.  BRCA1 testing in families with hereditary breast-ovarian cancer. A prospective study of patient decision making and outcomes. , 1996, JAMA.

[26]  K. Nathanson,et al.  Adjusting the estimated proportion of breast cancer cases associated with BRCA1 and BRCA2 mutations: Public health implications , 2005, Genetics in Medicine.

[27]  D. Berry,et al.  Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. , 1998, American journal of human genetics.

[28]  J. E. Nash,et al.  Psychological responses to BRCA1 mutation testing: preliminary findings. , 1997, Health psychology : official journal of the Division of Health Psychology, American Psychological Association.

[29]  M. Skolnick,et al.  Statement of the American Society of Clinical Oncology : Genetic testing for cancer susceptibility. Commentaries , 1996 .