Highlights
- •Germline mutations are more frequent among women with breast and uterine cancer compared to women with either cancer alone.
- •Genes most frequently mutated in women with breast and uterine cancer have published management guidelines that impact care.
- •Multigene panel testing is warranted for women with breast and uterine cancer.
Abstract
Objective
We explored the germline mutation spectrum and prevalence among 1650 women with breast
and uterine cancer (BUC) who underwent multi-gene hereditary cancer panel testing
at a single commercial laboratory.
Methods
The combined frequency of mutations in 23 BC and/or UC genes was compared between
BUC cases and control groups with (1) no personal cancer history; (2) BC only; and
(3) UC only using logistic regression.
Results
Fourteen percent (n = 231) of BUC cases tested positive for mutations in BC and/or
UC genes and were significantly more likely to test positive than individuals with
BC only (P < 0.001), UC only (P < 0.01), or unaffected controls (P < 0.001). Analysis
of gene-specific mutation frequencies revealed that MSH6, CHEK2, BRCA1, BRCA2, ATM, PMS2, PALB2 and MSH2 were most frequently mutated among BUC cases. Compared to BC only, BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN mutations were more frequent among BUC; however, only ATM mutations were more frequent among BUC compared to UC only. All of the more commonly
mutated genes have published management guidelines to guide clinical care. Of patients
with a single mutation in a gene with established testing criteria (n = 152), only
81.6% met their respective criteria, and 65.8% met criteria for multiple syndromes.
Conclusions
Women with BUC are more likely to carry hereditary cancer gene mutations than women
with breast or uterine cancer alone, potentially warranting expanded genetic testing
for these women. Most mutations found via multi-gene panel testing in women with BUC
have accompanying published management guidelines and significant implications for
clinical care.
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Article info
Publication history
Published online: January 03, 2019
Accepted:
December 24,
2018
Received in revised form:
December 21,
2018
Received:
September 17,
2018
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
