Researchers criticize study calling for expansion of genetic testing for breast cancer

Researchers at the University of Cambridge have criticised a recent study calling into question guidelines on genetic testing for hereditary breast cancer.

In an article published in the Journal of Clinical Oncology in December 2018 entitled “Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?”, 27 US researchers argued for expanded genetic testing in all patients with a diagnosis of breast cancer. Their argument rested on the finding that of patients who met National Comprehensive Cancer Network (NCCN) guidelines, 9.39% had a pathogenic/likely pathogenic variant, whilst of patients who did not meet guidelines, 7.9% had one of these variants.

In a letter published today in the same journal, Dr. Marc Tischkowitz from the Department of Medical Genetics at the University of Cambridge and Dr. Amy Taylor from Cambridge University Hospitals, claim that the study is flawed and point out that a third of the authors have potential conflicts of interest.

Drs Tischkowitz and Taylor point out that the US researchers have included in their calculations many variants in genes that have no definite proven association with an increased risk of breast cancer. Reanalysing the data including only variants in genes with definitive evidence for breast cancer susceptibility brings the figures of patients with a pathogenic/likely pathogenic variant down to 6.47% for those who met NCCN guidelines and 3.75% for those who did not.

“Not surprisingly, since the guidelines are intended to identify patients at high risk, the majority of variants identified in patients who did not meet guidelines were in [moderate risk genes], which do not impact on surgical management,” they write.

In addition, the Cambridge researchers say that in expanded genetic testing, an “unacceptably high” number of patients (54%) will test positive for variants of uncertain significance (VUS).

“These results take time to interpret and explain to patients, and may require follow-up, further testing, or review in case of reclassification. Of even greater concern, they are frequently misinterpreted, leading to inappropriate clinical management.”

Dr. Taylor adds: “Indiscriminate expanded panel testing not only has financial implications, but can lead of results that are difficult to interpret even for healthcare professionals, and may result in unnecessary surgery. Until we understand more about the genetics of breast cancer, we think it is unnecessary—and even unwise—to expand genetic testing.”

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