Highlights
- •17% and 20% of women had mutations and VUS in cancer predisposition genes.
- •Surgeries did not differ between women with VUS and benign findings.
- •78% of women with mutations in moderate risk genes underwent prophylactic surgery.
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
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Article info
Publication history
Published online: July 13, 2022
Accepted:
July 10,
2022
Received in revised form:
June 10,
2022
Received:
April 5,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
