Contribution of large genomic BRCA1 alterations to early-onset breast cancer selected for family history and tumour morphology: a report from The Breast Cancer Family Registry

Smith, Letitia, Tesoriero, Andrea A., Wong, Ee M., Ramus, Susan J., O'Malley, Frances P., Mulligan, Anna Marie, Terry, Mary Beth, Senie, Ruby T., Santella, Regina M., John, Esther M., Andrulis, Irene L., Ozcelik, Hilmi, Daly, Mary B., Godwin, Andrew K., Buys, Saundra S., Fox, Stephen, Goldgar, David E., Giles, Graham G., Hopper, John L., and Southey, Melissa C. (2011) Contribution of large genomic BRCA1 alterations to early-onset breast cancer selected for family history and tumour morphology: a report from The Breast Cancer Family Registry. Breast Cancer Research, 13 (1). R14.

[img]
Preview
PDF (Published Version) - Published Version
Available under License Creative Commons Attribution.

Download (265kB) | Preview
View at Publisher Website: http://dx.doi.org/10.1186/bcr2822
 
7
86


Abstract

Introduction: Selecting women affected with breast cancer who are most likely to carry a germline mutation in BRCA1 and applying the most appropriate test methodology remains challenging for cancer genetics services. We sought to test the value of selecting women for BRCA1 mutation testing on the basis of family history and/or breast tumour morphology criteria as well as the value of testing for large genomic alterations in BRCA1.

Methods: We studied women participating in the Breast Cancer Family Registry (BCFR), recruited via population-based sampling, who had been diagnosed with breast cancer before the age of 40 years who had a strong family history of breast or ovarian cancer (n = 187) and/or a first primary breast tumour with morphological features consistent with carrying a BRCA1 germline mutation (n = 133; 37 met both criteria). An additional 184 women diagnosed before the age of 40 years who had a strong family history of breast or ovarian cancer and who were not known to carry a germline BRCA1 mutation were selected from among women who had been recruited into the BCFR from clinical genetics services. These 467 women had been screened for BRCA1 germline mutations, and we expanded this testing to include a screen for large genomic BRCA1 alterations using Multiplex Ligation-dependent Probe Amplification.

Results: Twelve large genomic BRCA1 alterations were identified, including 10 (4%) of the 283 women selected from among the population-based sample. In total, 18 (12%), 18 (19%) and 16 (43%) BRCA1 mutations were identified in the population-based groups selected on the basis of family history only (n = 150), the group selected on the basis of tumour morphology only (n = 96) and meeting both criteria (n = 37), respectively.

Conclusions: Large genomic alterations accounted for 19% of all BRCA1 mutations identified. This study emphasises the value of combining information about family history, age at diagnosis and tumour morphology when selecting women for germline BRCA1 mutation testing as well as including a screen for large genomic alterations.

Item ID: 35572
Item Type: Article (Research - C1)
ISSN: 1465-542X
Additional Information:

Copyright © 2011 Smith et al.; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Funders: National Cancer Institute, National Institutes of Health, Breast Cancer Family Registry (BCFR), Cancer Care Ontario, Columbia University, Fox Chase Cancer Center, Huntsman Cancer Institute, Northern California Cancer Center, University of Melbourne, Research Triangle Institute Informatics Support Center
Projects and Grants: National Institutes of Health (RFA-CA-06-503), Cancer Care Ontario (grant U01 CA69467), Columbia University (grant U01 CA69398), Fox Chase Cancer Center (grant U01 CA69631), Huntsman Cancer Institute (grant U01 CA69446), Northern California Cancer Center (grant U01 CA69417), University of Melbourne (grant U01 CA69638), Research Triangle Institute Informatics Support Center (RFP N02PC45022-46).
Date Deposited: 01 Oct 2014 15:51
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111203 Cancer Genetics @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111706 Epidemiology @ 25%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110316 Pathology (excl Oral Pathology) @ 25%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
Downloads: Total: 86
Last 12 Months: 22
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page