Expanding the Search for Germline Pathogenic Variants for Breast Cancer. How Far Should We Go and How High Should We Jump? The Missed Opportunity!

Overview

Journal Oncol Rev

Specialty Oncology

Date 2021 Jul 16

PMID 34267891

Citations 3

Authors

Hikmat Abdel-Razeq

Affiliations

Soon will be listed here.

Abstract

Since the identification of and genes 3 decades ago, genetic testing and genetic counseling have become an integral part of routine clinical practice. The risk of breast cancer among carriers of germline pathogenic variants, like and , is well established. Risk-reducing interventions, including bilateral mastectomies and salpingo-oophorectomies are both effective and have become more acceptable. Many researchers and professional societies view current guidelines as restrictive and may miss many at-risk women, and are calling to expand testing to include all patients with breast cancer, regardless of their personal or family history of cancer, while others are calling for wider adoption to even include all healthy women at age 30 or older. This review will address expanding testing in two directions; horizontally to include more patients, and even healthy women, and vertically to include more genes using next-generation sequencing-based multi-gene panel testing.

Citing Articles

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Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer.

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References

Rebbeck T, Lynch H, Neuhausen S, Narod S, Veer L, Garber J . Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002; 346(21):1616-22. DOI: 10.1056/NEJMoa012158. View

Manchanda R, Sun L, Patel S, Evans O, Wilschut J, de Freitas Lopes A . Economic Evaluation of Population-Based Mutation Testing across Multiple Countries and Health Systems. Cancers (Basel). 2020; 12(7). PMC: 7409094. DOI: 10.3390/cancers12071929. View

Pharoah P, Antoniou A, Bobrow M, Zimmern R, Easton D, Ponder B . Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet. 2002; 31(1):33-6. DOI: 10.1038/ng853. View

Manchanda R, Patel S, Gordeev V, Antoniou A, Smith S, Lee A . Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women. J Natl Cancer Inst. 2018; 110(7):714-725. DOI: 10.1093/jnci/djx265. View

Beitsch P, Whitworth P, Hughes K, Patel R, Rosen B, Compagnoni G . Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?. J Clin Oncol. 2018; 37(6):453-460. PMC: 6380523. DOI: 10.1200/JCO.18.01631. View

Manchanda R, Legood R, Burnell M, McGuire A, Raikou M, Loggenberg K . Cost-effectiveness of population screening for BRCA mutations in Ashkenazi jewish women compared with family history-based testing. J Natl Cancer Inst. 2014; 107(1):380. PMC: 4301704. DOI: 10.1093/jnci/dju380. View

Daly M, Pal T, Berry M, Buys S, Dickson P, Domchek S . Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021; 19(1):77-102. DOI: 10.6004/jnccn.2021.0001. View

Vukovic P, Peccatori F, Massarotti C, Miralles M, Beketic-Oreskovic L, Lambertini M . Preimplantation genetic testing for carriers of BRCA1/2 pathogenic variants. Crit Rev Oncol Hematol. 2020; 157:103201. DOI: 10.1016/j.critrevonc.2020.103201. View

Samadder N, Riegert-Johnson D, Boardman L, Rhodes D, Wick M, Okuno S . Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome. JAMA Oncol. 2020; 7(2):230-237. PMC: 7600058. DOI: 10.1001/jamaoncol.2020.6252. View

10.

Robson M, Tung N, Conte P, Im S, Senkus E, Xu B . OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019; 30(4):558-566. PMC: 6503629. DOI: 10.1093/annonc/mdz012. View

11.

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

12.

Litton J, Rugo H, Ettl J, Hurvitz S, Goncalves A, Lee K . Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med. 2018; 379(8):753-763. PMC: 10600918. DOI: 10.1056/NEJMoa1802905. View

13.

Sun L, Brentnall A, Patel S, Buist D, Bowles E, Evans D . A Cost-effectiveness Analysis of Multigene Testing for All Patients With Breast Cancer. JAMA Oncol. 2019; 5(12):1718-1730. PMC: 6777250. DOI: 10.1001/jamaoncol.2019.3323. View

14.

Childers C, Childers K, Maggard-Gibbons M, Macinko J . National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer. J Clin Oncol. 2017; 35(34):3800-3806. PMC: 5707208. DOI: 10.1200/JCO.2017.73.6314. View

15.

Lincoln S, Kobayashi Y, Anderson M, Yang S, Desmond A, Mills M . A Systematic Comparison of Traditional and Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Genes in More Than 1000 Patients. J Mol Diagn. 2015; 17(5):533-44. DOI: 10.1016/j.jmoldx.2015.04.009. View

16.

Rebbeck T, Friebel T, Lynch H, Neuhausen S, van t Veer L, Garber J . Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2004; 22(6):1055-62. DOI: 10.1200/JCO.2004.04.188. View

17.

LaDuca H, Stuenkel A, Dolinsky J, Keiles S, Tandy S, Pesaran T . Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. Genet Med. 2014; 16(11):830-7. PMC: 4225457. DOI: 10.1038/gim.2014.40. View

18.

Manchanda R, Blyuss O, Gaba F, Gordeev V, Jacobs C, Burnell M . Current detection rates and time-to-detection of all identifiable carriers in the Greater London population. J Med Genet. 2018; 55(8):538-545. DOI: 10.1136/jmedgenet-2017-105195. View

19.

Hall M, Olopade O . Disparities in genetic testing: thinking outside the BRCA box. J Clin Oncol. 2006; 24(14):2197-203. DOI: 10.1200/JCO.2006.05.5889. View

20.

Derks-Smeets I, Gietel-Habets J, Tibben A, Tjan-Heijnen V, Meijer-Hoogeveen M, Geraedts J . Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with hereditary breast and ovarian cancer. Hum Reprod. 2014; 29(5):1103-12. DOI: 10.1093/humrep/deu034. View