A recent case study showed that up to 14% of patients with metastatic breast cancer possessed a higher number of hereditary risk genes in multi-tests. Several pathogenic and probably pathogenic germline variants were found, including BRCA1 and BRCA2 mutations.
The case series included a total of 100 patients who had been diagnosed with metastatic breast cancer. All participating women received a germline test, which included a total of 30 genes, irrespective of the National Comprehensive Cancer Network’s (NCCN) guideline recommendations.
To date, multi-test methods are not yet recommended in all cases in the USA by the NCCN. This is no longer an acceptable circumstance, as the authors of the current study believe on the basis of new findings.
The researchers argued that the test criteria for germline variants should be much broader. For example, the study showed that in some cases, BRCA1 and BRCA2 mutations were not detected simply by adherence to the NCCN test criteria. In addition, new risk variants were found in genes, such as ATM, BRIP1 or CHEK2.
A total of 14 out of 100 women (= 14%) showed pathogenic or probably pathogenic gene variants. In 43% of the cases (n = 6), the NCCN recommendations for genetic testing were not sufficient to detect these variants.
In detail, 6 of 14 participants showed BRCA mutations and 1 of 14 each showed an ATM, a BRIP1 or CHEK2 variant. In addition, more than one fifth (21%) of the women possessed gene variants that could not be assigned to any known risk according to the current state of knowledge.
Since the present study was a monocentric case series, it cannot be ruled out that region-specific artifacts could have occurred. It would be possible, for example, that there is an accumulation of certain genetic variations in this monocentric case.
At the same time, however, the very small sample size could have led to underestimating the true prevalence of the hereditary gene variants.
The US FDA had previously approved PARP for the treatment of HER2/ERBB2 double-negative breast cancer if the pathological gene variants of BRCA1 or BRCA2 were found simultaneously in the tumor.
This implies that multigene tests may also be therapeutically relevant in the presence of hereditary gene variants in metastatic breast cancer. For metastatic prostate carcinoma, which has shown similar findings to breast cancer, such a procedure was recently included in the NCCN guidelines as a recommendation.
Source:
Stuttgen K et al., Pathogenic Germline Variants in Patients With Metastatic Breast Cancer. JAMA Oncol 2019 [Epub ahead of print]; doi: 10.1001/jamaoncol.2019.3116