GERMLINE PREDISPOSITION : Tumour-only sequencing detects both inherited and acquired variants, mandating germline testing in appropriate cases.

Kevin Sovet

March 24, 2020

SCIENTIFIC

Tumour-only sequencing detects both inherited and acquired variants, mandating germline testing in appropriate cases. In a US study, 31% of patients with tumour-detected pathogenic BRCA1/2 mutations were not advised to undergo germline testing.

 

Germline Testing for Patients With BRCA1/2 Mutations on Somatic Tumor Testing

JNCI Cancer Spectrum, Volume 4, Issue 1, February 2020, pkz095, https://doi.org/10.1093/jncics/pkz095

 

Abstract

Background

The National Comprehensive Cancer Network (NCCN) recommends germline testing for pathogenic BRCA1/2 mutations identified by somatic tumor sequencing. The aim of this study was to explore whether patients at Stanford with somatic BRCA1/2 mutations were recommended germline testing in accordance with NCCN guidelines.

Methods

We retrospectively collected all Stanford patients with BRCA1/2 mutations found by tumor sequencing. Medical records were reviewed for each patient to identify those recommended germline testing. A multivariable logistic regression model was fit associating baseline characteristics with whether or not a recommendation was made.

Results

Of 164 participants, 51 (31.1%) had no recommendation for germline testing. Of the 97 available germline-testing results, 54 (55.7%) were positive for pathogenic BRCA1/2 mutations. After adjusting for possible confounders, patients with genitourinary cancer (odds ratio [OR] = 0.03, 95% confidence interval [CI] = 0.00 to 0.03; P =.003), lung cancer (OR = 0.04, 95% CI = 0.01 to 0.21; P <.001), sarcoma (OR = 0.02, 95% CI = 0.00 to 0.14; P <.001), skin cancer (OR = 0.01, 95% CI = 0.98 to 1.03; P =.002), or “other” diagnoses (OR = 0.01, 95% CI = 0.00 to 0.16; P <.001) were statistically significantly less likely to be recommended germline testing compared with patients with breast or gynecological cancers.

Conclusions

Our study highlights the importance of provider education outside of the oncologic specialties typically associated with BRCA-related cancers and continued exploration of referrals to genetics for germline testing on the basis of somatic findings.

more info : https://academic.oup.com/jncics/article/4/1/pkz095/5620725