TY - JOUR
T1 - Mammographic density does not differ between unaffected BRCA1/2 mutation carriers and women at low-to-average risk of breast cancer
AU - Gierach, Gretchen L.
AU - Loud, Jennifer T.
AU - Chow, Catherine K.
AU - Prindiville, Sheila A.
AU - Eng-Wong, Jennifer
AU - Soballe, Peter W.
AU - Giambartolomei, Claudia
AU - Mai, Phuong L.
AU - Galbo, Claudia E.
AU - Nichols, Kathryn
AU - Calzone, Kathleen A.
AU - Vachon, Celine
AU - Gail, Mitchell H.
AU - Greene, Mark H.
N1 - Funding Information:
K. A. Calzone Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA e-mail: calzonek@mail.nih.gov
Funding Information:
Acknowledgments The Breast Imaging Study (NCI Protocol #01-C-009); The Susceptibility to Breast Cancer Study (NCI Protocol #00-C-0079/NNMC Protocol #NNMC.2000.0010). We wish to thank Ruthann Giusti, Christine Mueller, and Paul Han for clinical support; Nicole Dupree, Jason Hu, Beth Mittl, Usha Singh, and Andrea Wilson for their help in data preparation; Pamela Klein for the original design of the NCI/NNMC Susceptibility to Breast Cancer Study; and Fang Fang Wu for the Cumulus density assessments. Special thanks to all our study participants, without whose cooperation this study could not have been done. Financial Support: This project was supported by the Intramural Research Program of the National Cancer Institute, and by contracts NO2-CP-11019-50 and NO2-CP-65504-50 with Westat, Inc. Dr. Gierach was supported by the NCI Cancer Prevention Fellowship Program. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.
Funding Information:
S. A. Prindiville Coordinating Center for Clinical Trials, Office of the Director, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA e-mail: prindivs@mail.nih.gov
Funding Information:
G. L. Gierach Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics and Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
PY - 2010/8
Y1 - 2010/8
N2 - Elevated mammographic density (MD) is one of the strongest risk factors for sporadic breast cancer. Epidemiologic evidence suggests that MD is, in part, genetically determined; however, the relationship between MD and BRCA1/2 mutation status is equivocal. We compared MD in unaffected BRCA1/2 mutation carriers enrolled in the U.S. National Cancer Institute's Clinical Genetics Branch's Breast Imaging Study (n = 143) with women at low-to-average breast cancer risk enrolled in the same study (n = 29) or the NCI/National Naval Medical Center's Susceptibility to Breast Cancer Study (n = 90). The latter were BRCA mutation-negative members of mutation-positive families or women with no prior breast cancer, a Pedigree Assessment Tool score <8 (i.e., low risk of a hereditary breast cancer syndrome) and a Gail score <1.67. A single experienced mammographer measured MD using a computer-assisted thresholding method. We collected standard breast cancer risk factor information in both studies. Unadjusted mean percent MD was higher in women with BRCA1/2 mutations compared with women at low-to-average breast cancer risk (37.3% vs. 33.4%; P = 0.04), but these differences disappeared after adjusting for age and body mass index (34.9% vs. 36.3%; P = 0.43). We explored age at menarche, nulliparity, age at first birth, menopausal status, number of breast biopsies, and exposure to exogenous hormonal agents as potential confounders of the MD and BRCA1/2 association. Taking these factors into account did not significantly alter the results of the age/body mass index-adjusted analysis. Our results do not provide support for an independent effect of BRCA1/2 mutation status on mammographic density.
AB - Elevated mammographic density (MD) is one of the strongest risk factors for sporadic breast cancer. Epidemiologic evidence suggests that MD is, in part, genetically determined; however, the relationship between MD and BRCA1/2 mutation status is equivocal. We compared MD in unaffected BRCA1/2 mutation carriers enrolled in the U.S. National Cancer Institute's Clinical Genetics Branch's Breast Imaging Study (n = 143) with women at low-to-average breast cancer risk enrolled in the same study (n = 29) or the NCI/National Naval Medical Center's Susceptibility to Breast Cancer Study (n = 90). The latter were BRCA mutation-negative members of mutation-positive families or women with no prior breast cancer, a Pedigree Assessment Tool score <8 (i.e., low risk of a hereditary breast cancer syndrome) and a Gail score <1.67. A single experienced mammographer measured MD using a computer-assisted thresholding method. We collected standard breast cancer risk factor information in both studies. Unadjusted mean percent MD was higher in women with BRCA1/2 mutations compared with women at low-to-average breast cancer risk (37.3% vs. 33.4%; P = 0.04), but these differences disappeared after adjusting for age and body mass index (34.9% vs. 36.3%; P = 0.43). We explored age at menarche, nulliparity, age at first birth, menopausal status, number of breast biopsies, and exposure to exogenous hormonal agents as potential confounders of the MD and BRCA1/2 association. Taking these factors into account did not significantly alter the results of the age/body mass index-adjusted analysis. Our results do not provide support for an independent effect of BRCA1/2 mutation status on mammographic density.
KW - Breast cancer risk
KW - Breast cancer screening
KW - Gene, BRCA1
KW - Gene, BRCA2
KW - Genetic predisposition to disease
KW - Mammographic density
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U2 - 10.1007/s10549-010-0749-7
DO - 10.1007/s10549-010-0749-7
M3 - Article
C2 - 20130984
AN - SCOPUS:77955772783
SN - 0167-6806
VL - 123
SP - 245
EP - 255
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -