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 Jobsen, Sabine Siesling, Rob A.E.M. Tollenaar, Flora E. van Leeuwen, Marjanka K. Schmidt

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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.

Original languageEnglish
Pages (from-to)409-418
Number of pages10
JournalJournal of clinical oncology
Volume34
Issue number5
DOIs
Publication statusPublished - 10 Feb 2016

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Breast Neoplasms
Mutation
Counseling
Odds Ratio
Population

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van den Broek, A. J., Van't Veer, L. J., Hooning, M. J., Cornelissen, S., Broeks, A., Rutgers, E. J., ... Schmidt, M. K. (2016). Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers. Journal of clinical oncology, 34(5), 409-418. https://doi.org/10.1200/JCO.2015.62.3942
van den Broek, Alexandra J. ; Van't Veer, Laura J. ; Hooning, Maartje J. ; Cornelissen, Sten ; Broeks, Annegien ; Rutgers, Emiel J. ; Smit, Vincent T.H.B.M. ; Cornelisse, Cees J. ; Van Beek, Mike ; Janssen-Heijnen, Maryska L. ; Seynaeve, Caroline ; Westenend, Pieter J. ; Jobsen, Jan ; Siesling, Sabine ; Tollenaar, Rob A.E.M. ; van Leeuwen, Flora E. ; Schmidt, Marjanka K. / Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers. In: Journal of clinical oncology. 2016 ; Vol. 34, No. 5. pp. 409-418.
@article{ce53ff5b31df47a597566d9e0c881873,
title = "Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers",
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.",
author = "{van den Broek}, {Alexandra J.} and {Van't Veer}, {Laura J.} and Hooning, {Maartje J.} and Sten Cornelissen and Annegien Broeks and Rutgers, {Emiel J.} and Smit, {Vincent T.H.B.M.} and Cornelisse, {Cees J.} and {Van Beek}, Mike and Janssen-Heijnen, {Maryska L.} and Caroline Seynaeve and Westenend, {Pieter J.} and Jan Jobsen and Sabine Siesling and Tollenaar, {Rob A.E.M.} and {van Leeuwen}, {Flora E.} and Schmidt, {Marjanka K.}",
year = "2016",
month = "2",
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doi = "10.1200/JCO.2015.62.3942",
language = "English",
volume = "34",
pages = "409--418",
journal = "Journal of clinical oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
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}

van den Broek, AJ, Van't Veer, LJ, Hooning, MJ, Cornelissen, S, Broeks, A, Rutgers, EJ, Smit, VTHBM, Cornelisse, CJ, Van Beek, M, Janssen-Heijnen, ML, Seynaeve, C, Westenend, PJ, Jobsen, J, Siesling, S, Tollenaar, RAEM, van Leeuwen, FE & Schmidt, MK 2016, 'Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers' Journal of clinical oncology, vol. 34, no. 5, pp. 409-418. https://doi.org/10.1200/JCO.2015.62.3942

Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers. / van den Broek, Alexandra J.; Van't Veer, Laura J.; Hooning, Maartje J.; Cornelissen, Sten; Broeks, Annegien; Rutgers, Emiel J.; Smit, Vincent T.H.B.M.; Cornelisse, Cees J.; Van Beek, Mike; Janssen-Heijnen, Maryska L.; Seynaeve, Caroline; Westenend, Pieter J.; Jobsen, Jan; Siesling, Sabine; Tollenaar, Rob A.E.M.; van Leeuwen, Flora E.; Schmidt, Marjanka K.

In: Journal of clinical oncology, Vol. 34, No. 5, 10.02.2016, p. 409-418.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers

AU - van den Broek, Alexandra J.

AU - Van't Veer, Laura J.

AU - Hooning, Maartje J.

AU - Cornelissen, Sten

AU - Broeks, Annegien

AU - Rutgers, Emiel J.

AU - Smit, Vincent T.H.B.M.

AU - Cornelisse, Cees J.

AU - Van Beek, Mike

AU - Janssen-Heijnen, Maryska L.

AU - Seynaeve, Caroline

AU - Westenend, Pieter J.

AU - Jobsen, Jan

AU - Siesling, Sabine

AU - Tollenaar, Rob A.E.M.

AU - van Leeuwen, Flora E.

AU - Schmidt, Marjanka K.

PY - 2016/2/10

Y1 - 2016/2/10

N2 - 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.

AB - 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.

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van den Broek AJ, Van't Veer LJ, Hooning MJ, Cornelissen S, Broeks A, Rutgers EJ et al. Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers. Journal of clinical oncology. 2016 Feb 10;34(5):409-418. https://doi.org/10.1200/JCO.2015.62.3942