Influence of germline test results on surgical decision making in women with invasive breast cancer

Ashlee B Vargason; Clesson E Turner; Craig D Shriver; Rachel E Ellsworth

doi:10.1016/j.cancergen.2022.07.003

Influence of germline test results on surgical decision making in women with invasive breast cancer

Cancer Genet. 2022 Aug:266-267:81-85. doi: 10.1016/j.cancergen.2022.07.003. Epub 2022 Jul 13.

Authors

Ashlee B Vargason¹, Clesson E Turner², Craig D Shriver³, Rachel E Ellsworth⁴

Affiliations

¹ Breast Care Clinic, Department of Surgery, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD 20889, USA. Electronic address: Ashlee.B.Vargason.civ@mail.mil.
² National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Electronic address: clesson.turner@nih.gov.
³ Murtha Cancer Center/Research Program, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD 20889, USA; Department of Surgery, Uniformed Services University of the Health Sciences, 8901 Rockville Pike, Bethesda, MD 20889, USA. Electronic address: craig.shriver@usuhs.edu.
⁴ Murtha Cancer Center/Research Program, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD 20889, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr., Bethesda, MD 20817, USA. Electronic address: rachel.ellsworth.ctr@usuhs.edu.

PMID: 35868102
DOI: 10.1016/j.cancergen.2022.07.003

Abstract

Background: While therapeutic mastectomy with contralateral prophylactic mastectomy (TM+CPM) and/or bilateral salpingo-oophorectomy (BSO) are recommended for women with pathogenic variants (PV) in some cancer predisposition genes, evidence for the utility of these surgeries for women with PV in other genes currently is insufficient. In conjunction, current guidelines recommend that clinical management should not be influenced by a return of a variant of uncertain significance (VUS). Return of germline test results may, however, influence surgical decision making regardless of current guidelines. We thus evaluated surgical choices amongst a cohort of women with invasive breast cancer who underwent clinical genetic testing.

Methods: Germline test results and all surgical procedures were extracted for women who had unilateral invasive breast cancer and had clinical testing before definitive surgery (n = 591). Results were classified as pathogenic/likely pathogenic (PV, 17.1%), VUS (19.5%) or benign/likely benign (63.4%). Data were analyzed using chi-square tests with p<0.05 defining significance.

Results: Rates of TM+CPM and BSO were not significantly different for women with VUS compared to those with benign findings. Rates of TM+CPM were significantly higher for women with PV in BRCA1 and BRCA2, PALB2, PTEN and TP53, as well in genes with insufficient data to recommend risk-reducing mastectomy. Rates of BSO were significantly higher in women with PV in BRCA1 and BRCA2, PALB2, PTEN and TP53 and BRIP1, RAD51C and RAD51D compared to those with benign findings.

Conclusion: Overall, surgical choices for women with a VUS were more similar to those from women with benign variants than to those with PV, however, in the group with PV in genes for which insufficient evidence exists for the benefit of risk-reducing mastectomy, rates of TM+CPM were high. Thus, while the management of women with VUS is in agreement with ACMG guidelines, patients with mutations in other cancer genes demonstrate a preference for more aggressive breast surgeries.

Keywords: Pathogenic variant; Risk-reducing surgery; VUS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / genetics
Breast Neoplasms* / surgery
Decision Making
Female
Genes, BRCA2
Genetic Predisposition to Disease
Genetic Testing
Germ Cells
Germ-Line Mutation
Humans
Mastectomy