Excess Risk for Contralateral Breast Cancer in CHEK2*1100delC Germline Mutation Carriers

Broeks, Annegien; Witte, Lot de; Nooijen, Anke; Huseinovic, Angelina; Klijn, Jan G.M.; Leeuwen, Flora E. van; Russell, Nicola S.; Veer, Laura J. van’t

doi:10.1023/b:brea.0000010697.49896.03

Cited by 64 publications

(59 citation statements)

References 13 publications

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“…5,[13][14][15][16][17][18][19] For homozygous carriers, our observations indicate that (contralateral) breast cancer risk may be as high as to justify preventive mastectomy (or at least intensified screening), but longitudinal studies on more cases are needed to arrive at more accurate risk estimates.…”

Section: Discussionmentioning

confidence: 93%

“…Homozygous wild-type patients are all homozygous wild-type patients from the ORIGO cohort for whom follow-up was available. 15,18,20 In 1100delC homozygotes, this risk seems comparable or even higher, with potential consequences for clinical management.…”

Section: Discussionmentioning

confidence: 99%

“…One study has reported an increased contralateral breast cancer risk when heterozygous patients had received radiotherapy as part of the treatment for their first breast tumor; another reported a similar but not statistically significant tendency. 15,19 Genotyping of larger cohorts is needed to better understand the effect of different treatments on breast cancer patients carrying the 1100delC allele. In the future, this can lead to personalized treatment strategies for 1100delC heterozygous and homozygous patients.…”

Section: Discussionmentioning

confidence: 99%

“…3,[10][11][12][13] Breast cancer patients heterozygous for 1100delC also have an increased risk of developing contralateral breast cancer when compared with wild-type breast cancer patients. 5,[13][14][15][16][17][18][19][20] The contralateral breast cancer risk may be even higher when radiotherapy has been given to treat the first tumor. 15,19 It must be noted that in women who also carry a pathogenic BRCA1/2 mutation the 1100delC allele does not seem to modify breast cancer risk.…”

Section: Introductionmentioning

confidence: 99%

“…5,[13][14][15][16][17][18][19][20] The contralateral breast cancer risk may be even higher when radiotherapy has been given to treat the first tumor. 15,19 It must be noted that in women who also carry a pathogenic BRCA1/2 mutation the 1100delC allele does not seem to modify breast cancer risk. 3,14,21 An association of the 1100delC allele with increased colon cancer and prostate cancer risk has been described, while an association with melanoma could not be found.…”

Section: Introductionmentioning

confidence: 99%

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CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

et al. 2013

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The 1100delC mutation in the CHEK2 gene has a carrier frequency of up to 1.5% in individuals from North-West Europe. Women heterozygous for 1100delC have an increased breast cancer risk (odds ratio 2.7). To explore the prevalence and clinical consequences of 1100delC homozygosity in the Netherlands, we genotyped a sporadic breast cancer hospital-based cohort, a group of non-BRCA1/2 breast cancer families, and breast tumors from a tumor tissue bank. Three 1100delC homozygous patients were found in the cohort of 1434 sporadic breast cancer patients, suggesting an increased breast cancer risk for 1100delC homozygotes (odds ratio 3.4, 95% confidence interval 0.4-32.6, P ¼ 0.3). Another 1100delC homozygote was found in 592 individuals from 108 non-BRCA1/2 breast cancer families, and two more were found after testing 1706 breast tumors and confirming homozygosity on their wild-type DNA. Follow-up data was available for five homozygous patients, and remarkably, three of them had developed contralateral breast cancer. A possible relationship between 1100delC and lung cancer risk was investigated in 457 unrelated lung cancer patients but could not be confirmed. Due to the small number of 1100delC homozygotes identified, the breast cancer risk estimate associated with this genotype had limited accuracy but is probably higher than the risk in heterozygous females. Screening for CHEK2 1100delC could be beneficial in countries with a relatively high allele frequency.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

et al. 2013

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Contralateral recurrence and prognostic factors in familial non-BRCA1/2-associated breast cancer

Tilanus-Linthorst

Alves

Seynaeve³

et al. 2006

British Journal of Surgery

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Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer

et al. 2018

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Although multigene panel testing is increasingly common in patients with cancer, the relationship between its use among breast cancer patients with non‐BRCA mutations or variants of uncertain significance (VUS) and disease management decisions has not been well described. This study evaluated the rate and predictive factors of CPM patients who underwent multigene panel testing. Three hundred and fourteen patients with breast cancer who underwent multigene panel testing between 2014 and 2017 were included in the analysis. Of the 314 patients, 70 elected CPM. Election of CPM by gene status was as follows: BRCA carriers (42.3%), non‐BRCA carriers (30.1%), and VUS (10.6%). CPM election rates did not differ between non‐BRCA carriers and BRCA carriers (P = 0.6205). Among non‐BRCA carriers, negative hormone receptor status was associated with CPM (P = 0.0115). For those with a VUS, hormone receptor status was not associated with CPM (P = 0.1879). Although the rate of CPM between BRCA carriers and non‐BRCA carriers was not significantly different, the predictors of CPM were different in each group. Our analyses shed the light on the increasing use of CPM among patients who are non‐BRCA carriers as well those with a VUS. Our study elucidates the differing predictive factors of CPM election among BRCA carriers, non‐BRCA carries, and those with a VUS. Our findings reveal the need for providers to be cognizant that non‐BRCA genes and VUS drive women to elect CPM despite the lack of data for contralateral breast cancer risk associated with these genes.

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Excess Risk for Contralateral Breast Cancer in CHEK2*1100delC Germline Mutation Carriers

Cited by 64 publications

References 13 publications

CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

Contralateral recurrence and prognostic factors in familial non-BRCA1/2-associated breast cancer

Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer

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