TY - JOUR
T1 - Breast Cancer Survival of BRCA1/BRCA2 Mutation Carriers in a Hospital-Based Cohort of Young Women
AU - Schmidt, Marjanka K.
AU - van den Broek, Alexandra J.
AU - Tollenaar, Rob A. E. M.
AU - Smit, Vincent T. H. B. M.
AU - Westenend, Pieter J.
AU - Brinkhuis, Mariel
AU - Oosterhuis, Wolter J. W.
AU - Wesseling, Jelle
AU - Janssen-Heijnen, Maryska L.
AU - Jobsen, Jan J.
AU - Jager, Agnes
AU - Voogd, Adri C.
AU - van Leeuwen, Flora E.
AU - van 't Veer, Laura J.
PY - 2017/8
Y1 - 2017/8
N2 - Background: The primary aim of the study was to investigate prognosis and long-term survival in young breast cancer patients with a BRCA1 or BRCA2 germline mutation compared with noncarriers. The secondary aim was to investigate whether differences in survival originate from associations with tumor characteristics, second cancers, and/or treatment response.Methods: We established a cohort of invasive breast cancer patients diagnosed younger than age 50 years in 10 Dutch hospitals between 1970 and 2003. BRCA1/2 testing of most prevalent mutations was mainly done using DNA isolate from formalin-fixed paraffin-embedded nontumor tissue. Survival estimates were derived using Cox regression and competing risk models.Results: In 6478 breast cancer patients, we identified 3.2% BRCA1 and 1.2% BRCA2 mutation carriers. BRCA1 mutation carriers had a worse overall survival independent of clinico-pathological/treatment characteristics, compared with noncarriers (adjusted hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 0.97 to 1.47), though only statistically significant in the first five years of follow-up (adjusted HR = 1.40, 95% CI = 1.07 to 1.84). A large part of the worse survival was explained by incidence of ovarian cancers. Breast cancer-specific, disease-free, and metastasis-free survival results were less pronounced and mostly statistically nonsignificant but in the same direction with those of overall survival. Overall survival was worse, although not statistically significantly, within the ER-negative or ER-positive, grade 3, and small tumor subgroups. The worse survival was most pronounced in non-chemotherapy-treated patients (adjusted HR = 1.54, 95% CI = 1.08 to 2.19). Power for BRCA2 mutation carriers was limited; only after five years' follow-up overall survival was worse (adjusted HR = 1.47, 95% CI = 1.00 to 2.17).Conclusions: BRCA1/2 mutation carriers diagnosed with breast cancer before age 50 years are prone to a worse survival, which is partly explained by differences in tumor characteristics, treatment response, and second ovarian cancers.
AB - Background: The primary aim of the study was to investigate prognosis and long-term survival in young breast cancer patients with a BRCA1 or BRCA2 germline mutation compared with noncarriers. The secondary aim was to investigate whether differences in survival originate from associations with tumor characteristics, second cancers, and/or treatment response.Methods: We established a cohort of invasive breast cancer patients diagnosed younger than age 50 years in 10 Dutch hospitals between 1970 and 2003. BRCA1/2 testing of most prevalent mutations was mainly done using DNA isolate from formalin-fixed paraffin-embedded nontumor tissue. Survival estimates were derived using Cox regression and competing risk models.Results: In 6478 breast cancer patients, we identified 3.2% BRCA1 and 1.2% BRCA2 mutation carriers. BRCA1 mutation carriers had a worse overall survival independent of clinico-pathological/treatment characteristics, compared with noncarriers (adjusted hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 0.97 to 1.47), though only statistically significant in the first five years of follow-up (adjusted HR = 1.40, 95% CI = 1.07 to 1.84). A large part of the worse survival was explained by incidence of ovarian cancers. Breast cancer-specific, disease-free, and metastasis-free survival results were less pronounced and mostly statistically nonsignificant but in the same direction with those of overall survival. Overall survival was worse, although not statistically significantly, within the ER-negative or ER-positive, grade 3, and small tumor subgroups. The worse survival was most pronounced in non-chemotherapy-treated patients (adjusted HR = 1.54, 95% CI = 1.08 to 2.19). Power for BRCA2 mutation carriers was limited; only after five years' follow-up overall survival was worse (adjusted HR = 1.47, 95% CI = 1.00 to 2.17).Conclusions: BRCA1/2 mutation carriers diagnosed with breast cancer before age 50 years are prone to a worse survival, which is partly explained by differences in tumor characteristics, treatment response, and second ovarian cancers.
KW - INHERITED MUTATIONS
KW - BRCA1
KW - POPULATION
KW - RISK
KW - CHEMOTHERAPY
KW - PROGNOSIS
KW - IMPUTATION
KW - FAMILIES
KW - TRENDS
KW - GENES
U2 - 10.1093/jnci/djw329
DO - 10.1093/jnci/djw329
M3 - Article
SN - 0027-8874
VL - 109
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 8
M1 - 329
ER -