domingo, 28 de enero de 2018

Impact of Multigene Panel Testing on Surgical Decision Making in Breast Cancer Patients. - PubMed - NCBI

2018 Jan 19. pii: S1072-7515(18)30018-8. doi: 10.1016/j.jamcollsurg.2017.12.037. [Epub ahead of print]

Impact of Multigene Panel Testing on Surgical Decision Making in Breast Cancer Patients.

Pederson HJ1, Gopalakrishnan D2, Noss R3, Yanda C1, Eng C3, Grobmyer SR4.

Author information

Abstract

BACKGROUND:

With the advent of multi-gene panel testing for breast cancer patients, germline mutations with unknown association with cancer risk, known as variants of uncertain significance (VUS), are being increasingly identified. Some studies have shown higher rates of contralateral prophylactic mastectomies (CPM) in these patients despite lack of evidence to support this intervention. We analyzed surgical choices in patients who were identified to have VUS.

METHODS:

A retrospective review was performed of patients with TNBC treated at a single institution after multi-gene panel tests became available (09/01/2013- 02/28/2017). Rates of genetic testing, results of testing, and surgical decision making were evaluated. Χ2 or Fisher's exact test was used to compare categorical variables. P-value <0.05 was considered statistically significant.

RESULTS:

477 TNBC patients were identified. 331 met established criteria for genetic testing and 226 (68.3%) underwent genetic testing (multigene panel - 130, BRCA1/2 testing - 96); all of them received risk-appropriate genetic counseling and follow-up. Of these, 29(12.8%) patients had pathogenic mutations in BRCA1/2 or PALB2 (Mut+), 42(18.6%) had VUS (VUS+), and 155(68.6%) had no mutations identified (Mut-). VUS in 6/42 patients (14.3%) were later reclassified as normal variants. 88.0% of Mut+ patients underwent CPM, compared to 20.1% of Mut- and 21.4% of VUS+ patients (p <0.001 for both). Rates of CPM were not significantly different between VUS+ and Mut- (p=0.37). Multi-gene panel testing detected pathogenic mutations in non-breast cancer-associated genes in 6 patients, with significant management implications.

CONCLUSIONS:

When combined with risk-appropriate genetic counseling, detection of VUS did not lead to excessive CPM in this cohort of TNBC patients. Furthermore, panel testing detected mutations in non-breast cancer-associated genes which had significant implications on management and outcomes.