Cancer risks for BRCA1 and BRCA2 mutation carriers: Results from prospective analysis of EMBRACE
Citation:
Mavaddat, N. Peock, S. Frost, D. Ellis, S. Platte, R. Fineberg, E. Evans, D.G. Izatt, L. Eeles, R.A. Adlard, J. Davidson, R. Eccles, D. Cole, T. Cook, J. Brewer, C. Tischkowitz, M. Douglas, F. Hodgson, S. Walker, L. Porteous, M.E. Morrison, P.J. Side, L.E. Kennedy, M.J. Houghton, C. Donaldson, A. Rogers, M.T. Dorkins, H. Miedzybrodzka, Z. Gregory, H. Eason, J. Barwell, J. McCann, E. Murray, A. Antoniou, A.C. Easton, D.F., Cancer risks for BRCA1 and BRCA2 mutation carriers: Results from prospective analysis of EMBRACE, Journal of the National Cancer Institute, 105, 11, 2013, 812 - 822Download Item:
Abstract:
Background
Reliable estimates of cancer risk are critical for guiding management of
BRCA1
and
BRCA2
mutation carriers. The
aims of this study were to derive penetrance estimates for breast cancer, ovarian cancer, and contralateral breast
cancer in a prospective series of mutation carriers and to assess how these risks are modified by common breast
cancer susceptibility alleles.
Methods
Prospective cancer risks were estimated using a cohort of 978
BRCA1
and 909
BRCA2
carriers from the United
Kingdom. Nine hundred eighty-eight women had no breast or ovarian cancer diagnosis at baseline, 1509 women
were unaffected by ovarian cancer, and 651 had been diagnosed with unilateral breast cancer. Cumulative risks
were obtained using Kaplan–Meier estimates. Associations between cancer risk and covariables of interest were
evaluated using Cox regression. All statistical tests were two-sided.
Results
The average cumulative risks by age 70 years for
BRCA1
carriers were estimated to be 60% (95% confidence inter
-
val [CI] = 44% to 75%) for breast cancer, 59% (95% CI = 43% to 76%) for ovarian cancer, and 83% (95% CI = 69% to
94%) for contralateral breast cancer. For
BRCA2
carriers, the corresponding risks were 55% (95% CI = 41% to 70%)
for breast cancer, 16.5% (95% CI = 7.5% to 34%) for ovarian cancer, and 62% (95% CI = 44% to 79.5%) for contralat
-
eral breast cancer.
BRCA2
carriers in the highest tertile of risk, defined by the joint genotype distribution of seven
single nucleotide polymorphisms associated with breast cancer risk, were at statistically significantly higher risk
of developing breast cancer than those in the lowest tertile (hazard ratio = 4.1, 95% CI = 1.2 to 14.5;
P
= .02).
Conclusions
Prospective risk estimates confirm that
BRCA1
and
BRCA2
carriers are at high risk of developing breast, ovar
-
ian, and contralateral breast cancer. Our results confirm findings from retrospective studies that common breast
cancer susceptibility alleles in combination are predictive of breast cancer risk for
BRCA2
carriers
Author's Homepage:
http://people.tcd.ie/kennedmiDescription:
PUBLISHED
Author: KENNEDY, MICHAEL
Type of material:
Journal ArticleCollections
Series/Report no:
Journal of the National Cancer Institute105
11
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Full text availableKeywords:
breast canceDOI:
http://dx.doi.org/10.1093/jnci/djt095Metadata
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