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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish
Pages (from-to)81-85
Number of pages5
JournalCancer Genetics
StatePublished - Aug 2022
Externally publishedYes


  • Pathogenic variant
  • Risk-reducing surgery
  • VUS


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