Mutation rates in cancer susceptibility genes in patients with breast cancer with multiple primary cancers Journal Article
| Authors: | Maxwell, K. N.; Wenz, B. M.; Kulkarni, A.; Wubbenhorst, B.; D’Andrea, K.; Weathers, B.; Goodman, N.; Vijai, J.; Lilyquist, J.; Hart, S. N.; Slavin, T. P.; Schrader, K. A.; Ravichandran, V.; Thomas, T.; Hu, C.; Robson, M. E.; Peterlongo, P.; Bonanni, B.; Ford, J. M.; Garber, J. E.; Neuhausen, S. L.; Shah, P. D.; Bradbury, A. R.; DeMichele, A. M.; Offit, K.; Weitzel, J. N.; Couch, F. J.; Domchek, S. M.; Nathanson, K. L. |
| Article Title: | Mutation rates in cancer susceptibility genes in patients with breast cancer with multiple primary cancers |
| Abstract: | PURPOSE Women with breast cancer have a 4%-16% lifetime risk of a second primary cancer. Whether mutations in genes other than BRCA1/2 are enriched in patients with breast and another primary cancer over those with a single breast cancer (S-BC) is unknown. PATIENTS AND METHODS We identified pathogenic germline mutations in 17 cancer susceptibility genes in patients with BRCA1/2-negative breast cancer in 2 different cohorts: cohort 1, high-risk breast cancer program (multiple primary breast cancer [MP-BC], n = 551; S-BC, n = 449) and cohort 2, familial breast cancer research study (MP-BC, n = 340; S-BC, n = 1,464). Mutation rates in these 2 cohorts were compared with a control data set (Exome Aggregation Consortium [ExAC]). RESULTS Overall, pathogenic mutation rates for autosomal, dominantly inherited genes were higher in patients with MP-BC versus S-BC in both cohorts (8.5% v 4.9% [P = .02] and 7.1% v 4.2% [P = .03]). There were differences in individual gene mutation rates between cohorts. In both cohorts, younger age at first breast cancer was associated with higher mutation rates; the age of non–breast cancers was unrelated to mutation rate. TP53 and MSH6 mutations were significantly enriched in patients with MP-BC but not S-BC, whereas ATM and PALB2 mutations were significantly enriched in both groups compared with ExAC. CONCLUSION Mutation rates are at least 7% in all patients with BRCA1/2 mutation–negative MP-BC, regardless of age at diagnosis of breast cancer, with mutation rates up to 25% in patients with a first breast cancer diagnosed at age, 30 years. Our results suggest that all patients with breast cancer with a second primary cancer, regardless of age of onset, should undergo multigene panel testing. © 2020 by American Society of Clinical Oncology |
| Journal Title: | JCO Precision Oncology |
| Volume: | 4 |
| ISSN: | 2473-4284 |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2020-08-19 |
| Start Page: | 916 |
| End Page: | 925 |
| Language: | English |
| DOI: | 10.1200/po.19.00301 |
| PROVIDER: | scopus |
| PMCID: | PMC7496037 |
| PUBMED: | 32954205 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2020 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
-
788Offit -
676Robson -
211Joseph -
19Thomas -
38Ravichandran
Related MSK Work