3 years ago

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

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.


Germline gene variants of unknown significance (VUS) are associated with unknown cancer risk. We studied surgical decision making among breast cancer patients undergoing multigene panel testing who were found to have VUS. Patients with VUS did not have an increased rate of prophylactic mastectomy compared to patients with no genetic mutation.

Publisher URL: www.sciencedirect.com/science

DOI: S1072751518300188

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.