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J Clin Oncol. 2016 Feb 10;34(5):409-18. doi: 10.1200/JCO.2015.62.3942. Epub 2015 Dec 23.

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

Author information

1
Alexandra J. van den Broek, Laura J. van 't Veer, Sten Cornelissen, Annegien Broeks, Emiel J. Rutgers, Flora E. van Leeuwen, and Marjanka K. Schmidt, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam; Maartje J. Hooning and Caroline Seynaeve, Erasmus MC Cancer Institute, Rotterdam; Vincent T.H.B.M. Smit, Cees J. Cornelisse, and Rob A.E.M. Tollenaar, Leiden University Medical Center, Leiden; Mike van Beek, PAMM, Catharina Hospital, Eindhoven; Maryska L. Janssen-Heijnen, Netherlands Comprehensive Cancer Organization, Eindhoven, and VieCuri Medical Centre, Venlo; Pieter J. Westenend, Laboratory for Pathology, Dordrecht; Jan J. Jobsen, Medisch Spectrum Twente, Enschede; and Sabine Sieling, Netherlands Comprehensive Cancer Organization, Utrecht, Netherlands.
2
Alexandra J. van den Broek, Laura J. van 't Veer, Sten Cornelissen, Annegien Broeks, Emiel J. Rutgers, Flora E. van Leeuwen, and Marjanka K. Schmidt, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam; Maartje J. Hooning and Caroline Seynaeve, Erasmus MC Cancer Institute, Rotterdam; Vincent T.H.B.M. Smit, Cees J. Cornelisse, and Rob A.E.M. Tollenaar, Leiden University Medical Center, Leiden; Mike van Beek, PAMM, Catharina Hospital, Eindhoven; Maryska L. Janssen-Heijnen, Netherlands Comprehensive Cancer Organization, Eindhoven, and VieCuri Medical Centre, Venlo; Pieter J. Westenend, Laboratory for Pathology, Dordrecht; Jan J. Jobsen, Medisch Spectrum Twente, Enschede; and Sabine Sieling, Netherlands Comprehensive Cancer Organization, Utrecht, Netherlands. mk.schmidt@nki.nl.

Abstract

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.

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.

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.

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.

PMID:
26700119
DOI:
10.1200/JCO.2015.62.3942
[Indexed for MEDLINE]

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