Paired tumor sequencing and germline testing in breast cancer management: An experience of a single academic center.
breast cancer
cancer predisposition
clinical utility
genomic profiling
germline testing
next-generation sequencing
Journal
Cancer reports (Hoboken, N.J.)
ISSN: 2573-8348
Titre abrégé: Cancer Rep (Hoboken)
Pays: United States
ID NLM: 101747728
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
16
03
2020
revised:
05
08
2020
accepted:
06
08
2020
pubmed:
4
9
2020
medline:
30
11
2021
entrez:
4
9
2020
Statut:
ppublish
Résumé
Genetic testing for cancer predisposition is recommended to women with breast cancer who meet the criteria for such testing. After the FDA approvals of the poly ADP ribose polymerase (PARP) inhibitors, olaparib and talazoparib, for treatment of metastatic breast cancer, carrying germline mutations in BRCA1 and BRCA2 genes, the genetic testing result has become critical in their care. With the recent FDA approval of alpelisib for the treatment of PIK3CA-mutated hormone-receptor positive metastatic breast cancer, tumor molecular profiling to identify somatic mutations and potential molecularly targeted agents is increasingly utilized in the treatment of advanced breast cancer. Combining germline and somatic sequencing (paired testing) offers an advantage over a single technique approach. Our study evaluates the role of paired testing on the management of breast cancer patients. Forty-three breast cancer patients treated at Rush University Medical Center underwent paired germline and somatic variant testing in 2015 to 2017. A retrospective chart review was conducted with the analysis of demographic, clinical, and genomic data. Three actionable germline variants were found in the CHEK2 (2) and ATM (1) genes. 95% of tumors had somatic mutations. Seventy-seven percent of tumors had genomic alterations targetable with agents approved for breast cancer and 88% had molecular targets for agents approved for other cancers. Clinical examples of such use are described and potential future directions of tumor and paired testing are discussed. Germline variants were present in a relatively small patient group not routinely tested for inherited alterations. Potentially targetable somatic alterations were identified in the majority of breast cancers. Paired testing is a feasible and efficient approach that delivers valuable information for the care of breast cancer patients and eliminates serial testing.
Sections du résumé
BACKGROUND
Genetic testing for cancer predisposition is recommended to women with breast cancer who meet the criteria for such testing. After the FDA approvals of the poly ADP ribose polymerase (PARP) inhibitors, olaparib and talazoparib, for treatment of metastatic breast cancer, carrying germline mutations in BRCA1 and BRCA2 genes, the genetic testing result has become critical in their care. With the recent FDA approval of alpelisib for the treatment of PIK3CA-mutated hormone-receptor positive metastatic breast cancer, tumor molecular profiling to identify somatic mutations and potential molecularly targeted agents is increasingly utilized in the treatment of advanced breast cancer.
AIM
Combining germline and somatic sequencing (paired testing) offers an advantage over a single technique approach. Our study evaluates the role of paired testing on the management of breast cancer patients.
METHODS AND RESULTS
Forty-three breast cancer patients treated at Rush University Medical Center underwent paired germline and somatic variant testing in 2015 to 2017. A retrospective chart review was conducted with the analysis of demographic, clinical, and genomic data. Three actionable germline variants were found in the CHEK2 (2) and ATM (1) genes. 95% of tumors had somatic mutations. Seventy-seven percent of tumors had genomic alterations targetable with agents approved for breast cancer and 88% had molecular targets for agents approved for other cancers. Clinical examples of such use are described and potential future directions of tumor and paired testing are discussed.
CONCLUSIONS
Germline variants were present in a relatively small patient group not routinely tested for inherited alterations. Potentially targetable somatic alterations were identified in the majority of breast cancers. Paired testing is a feasible and efficient approach that delivers valuable information for the care of breast cancer patients and eliminates serial testing.
Identifiants
pubmed: 32881420
doi: 10.1002/cnr2.1287
pmc: PMC7941483
doi:
Substances chimiques
Checkpoint Kinase 2
EC 2.7.1.11
CHEK2 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1287Informations de copyright
© 2020 The Authors. Cancer Reports published by Wiley Periodicals LLC.
Références
Lancet Oncol. 2014 Mar;15(3):267-74
pubmed: 24508104
Clin Cancer Res. 2016 Aug 1;22(15):3764-73
pubmed: 26957554
N Engl J Med. 2017 Mar 9;376(10):917-927
pubmed: 28273028
Oncotarget. 2016 Oct 18;7(42):68206-68228
pubmed: 27626691
Curr Drug Targets. 2014 Jan;15(1):2-16
pubmed: 24387338
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
JAMA. 2017 Sep 5;318(9):825-835
pubmed: 28873162
EMBO Mol Med. 2009 Sep;1(6-7):315-22
pubmed: 20049735
J Natl Cancer Inst. 2014 Apr 28;106(5):
pubmed: 24777111
Int J Breast Cancer. 2016;2016:2469523
pubmed: 27822389
Cancer Rep (Hoboken). 2020 Dec;3(6):e1287
pubmed: 32881420
J Clin Oncol. 2011 Aug 1;29(22):3008-15
pubmed: 21709188
Lancet Oncol. 2015 Oct;16(13):1324-34
pubmed: 26342236
Histopathology. 2014 Apr;64(5):609-15
pubmed: 24382093
Arch Pathol Lab Med. 2016 Aug;140(8):815-24
pubmed: 27472240
JNCI Cancer Spectr. 2019 Nov 11;4(1):pkz095
pubmed: 32259017
NPJ Genom Med. 2016 Jan 13;1:15006
pubmed: 29263804
Cancer Discov. 2013 Feb;3(2):224-37
pubmed: 23220880
Hered Cancer Clin Pract. 2017 Jul 26;15:11
pubmed: 28770017
Nat Med. 2019 Oct;25(10):1526-1533
pubmed: 31570822
Nature. 2012 Oct 4;490(7418):61-70
pubmed: 23000897
Hered Cancer Clin Pract. 2011 Nov 15;9:10
pubmed: 22085629
Cancer Res. 2016 Nov 1;76(21):6253-6265
pubmed: 27803104
Nature. 2016 May 02;534(7605):47-54
pubmed: 27135926
Nat Med. 2018 May;24(5):628-637
pubmed: 29713086
JAMA Oncol. 2016 Jan;2(1):104-11
pubmed: 26556299
Adv Anat Pathol. 2014 Mar;21(2):100-7
pubmed: 24508693
Curr Oncol. 2018 Apr;25(2):e176-e180
pubmed: 29719442
J Clin Oncol. 2015 Nov 10;33(32):3817-25
pubmed: 26304871
Cancer Chemother Pharmacol. 2015 Dec;76(6):1113-32
pubmed: 26391154
Surg Oncol Clin N Am. 2017 Oct;26(4):791-797
pubmed: 28923231
Nature. 2020 Feb;578(7793):82-93
pubmed: 32025007
JAMA. 2015 Jan 13;313(2):165-73
pubmed: 25585328
JAMA Oncol. 2018 Oct 1;4(10):1335-1343
pubmed: 29902286
Curr Oncol Rep. 2017 May;19(5):35
pubmed: 28374222
N Engl J Med. 2017 Aug 10;377(6):523-533
pubmed: 28578601
NPJ Breast Cancer. 2017 Dec 6;3:49
pubmed: 29238749
J Clin Oncol. 2008 Jul 20;26(21):3631-7
pubmed: 18640941
J Clin Oncol. 2010 Jun 1;28(16):2784-95
pubmed: 20404251
Oncologist. 2016 Sep;21(9):1063-78
pubmed: 27384237
Clin Genet. 2018 Jan;93(1):41-51
pubmed: 28580595
Eur J Cancer. 2017 Sep;83:258-265
pubmed: 28756138