TY - JOUR
T1 - Cancer risks for BRCA1 and BRCA2 mutation carriers: Results from prospective analysis of EMBRACE
AU - Mavaddat, Nasim
AU - Peock, Susan
AU - Frost, Debra
AU - Ellis, Steve
AU - Platte, Radka
AU - Fineberg, Elena
AU - Evans, D. Gareth
AU - Izatt, Louise
AU - Eeles, Rosalind A.
AU - Adlard, Julian
AU - Davidson, Rosemarie
AU - Eccles, Diana
AU - Cole, Trevor
AU - Cook, Jackie
AU - Brewer, Carole
AU - Tischkowitz, Marc
AU - Douglas, Fiona
AU - Hodgson, Shirley
AU - Walker, Lisa
AU - Porteous, Mary E.
AU - Morrison, Patrick J.
AU - Side, Lucy E.
AU - Kennedy, M. John
AU - Houghton, Catherine
AU - Donaldson, Alan
AU - Rogers, Mark T.
AU - Dorkins, Huw
AU - Miedzybrodzka, Zosia
AU - Gregory, Helen
AU - Eason, Jacqueline
AU - Barwell, Julian
AU - McCann, Emma
AU - Murray, Alex
AU - Antoniou, Antonis C.
AU - Easton, Douglas F.
N1 - C1287/A10118, Cancer Research UK, United KingdomC1287/A11990, Cancer Research UK, United KingdomC5047/A8385, Arthritis Research UK, United Kingdom, Medical Research Council, United Kingdom
PY - 2013/6/5
Y1 - 2013/6/5
N2 - 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 interval [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 contralateral 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, ovarian, 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. © 2013 The Author.
AB - 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 interval [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 contralateral 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, ovarian, 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. © 2013 The Author.
U2 - 10.1093/jnci/djt095
DO - 10.1093/jnci/djt095
M3 - Article
C2 - 23628597
SN - 0027-8874
VL - 105
SP - 812
EP - 822
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 11
ER -
