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Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in BRCA1/2 Mutation Carriers.

Alexandra J van den Broek ,
Laura J van 't Veer ,
Maartje J Hooning ,
Sten Cornelissen ,
Annegien Broeks ,
Emiel J Rutgers ,
Vincent T H B M Smit ,
Cees J Cornelisse ,
Mike van Beek ,
Maryska L Janssen-Heijnen ,
Caroline Seynaeve ,
Pieter J Westenend ,
Jan J Jobsen ,
Sabine Siesling ,
Rob A E M Tollenaar ,
Flora E van Leeuwen ,
Marjanka K Schmidt

Abstract

PATIENTS AND METHODS

A cohort of 6,294 patients with invasive breast cancer diagnosed under 50 years of age and treated between 1970 and 2003 in 10 Dutch centers was tested for the most prevalent BRCA1/2 mutations. We report absolute risks and hazard ratios within the cohort from competing risk analyses.

CONCLUSION

Age at first breast cancer is a strong risk factor for cumulative CBC risk in BRCA1/2 mutation carriers. Considering the available evidence, age-specific risk estimates should be included in counseling.

RESULTS

After a median follow-up of 12.5 years, 578 CBCs were observed in our study population. CBC risk for BRCA1 and BRCA2 mutation carriers was two to three times higher than for noncarriers (hazard ratios, 3.31 [95% CI, 2.41 to 4.55; P < .001] and 2.17 [95% CI,1.22 to 3.85; P = .01], respectively). Ten-year cumulative CBC risks were 21.1% (95% CI, 15.4 to 27.4) for BRCA1, 10.8% (95% CI, 4.7 to 19.6) for BRCA2 mutation carriers and 5.1% (95% CI, 4.5 to 5.7) for noncarriers. Age at diagnosis of the first breast cancer was a significant predictor of CBC risk in BRCA1/2 mutation carriers only; those diagnosed before age 41 years had a 10-year cumulative CBC risk of 23.9% (BRCA1: 25.5%; BRCA2: 17.2%) compared with 12.6% (BRCA1: 15.6%; BRCA2: 7.2%) for those 41 to 49 years of age (P = .02); our review of published studies showed ranges of 24% to 31% before age 40 years (BRCA1: 24% to 32%; BRCA2:17% to 29%) and 8% to 21% after 40 years (BRCA1: 11% to 52%; BRCA2: 7% to 18%), respectively.

PURPOSE

To determine prospectively overall and age-specific estimates of contralateral breast cancer (CBC) risk for young patients with breast cancer with or without BRCA1/2 mutations.

More about this publication

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Volume 34
Issue nr. 5
Pages 409-18
Publication date 10-02-2016

Full text links

Publisher website (DOI) 10.1200/JCO.2015.62.3942
Europe PubMed Central 26700119
Pubmed 26700119

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