Should All Patients with Cancer Have Hereditary Genetic Testing?

New scientific evidence for patients with various cancers shows that germline (hereditary) genetic testing is beneficial. Such tests can identify mutations that may require a change in treatment and allow a targeted therapy to be tried, and can also give high-risk individuals and family members screening guidance.

What Is a Germline (Hereditary) Cancer Mutation?

Cancer is a group of diseases in which cells multiply uncontrollably as a result of the accumulation of certain genetic damage. Our genetic code, DNA, undergoes permanent changes that we call mutations; these mutations are broadly divided into two classes: somatic (in body cells) and germline (in sex cells) mutations. Somatic mutations occur throughout life after birth and are not passed on to subsequent generations. Germline mutations, on the other hand, are transmitted through sperm and eggs, which are germ cells, and pass from parents to children.

Listed below are the most common hereditary mutations known to be associated with cancer:

Emphasis on hereditary cancer testing at ASCO 2021

The new data come from a series of studies recently presented at the American Society of Clinical Oncology (ASCO) 2021 virtual annual meeting.

Patients with prostate cancer were included in a study (abstract 10504), which found that 10.8% of patients had pathogenic inherited genetic changes, with 15% of these variants requiring treatment with a PARP inhibitor because they were BRCA1/2 mutations, as the study found.

However, professionals working in oncology have been slow to adopt routine testing, and many studies have shown that many oncologists have not yet incorporated genetic testing into routine cancer care.

Colorectal cancer is a good example: clinical guidelines recommend germline (hereditary) genetic testing for all patients with this diagnosis. Yet a study involving 55,595 people found that only 6% of patients with colorectal cancer had been tested (abstract 10514).

• Related topic: HEREDITARY Mutations Cause 1 in Every 8 Cancers

Why Should Patients with Cancer Have Hereditary Genetic Testing?

Overly restrictive, complex and ineffective testing guidelines are a major barrier that excludes patients who would definitely benefit from testing.

Most professional guidelines are still based on information from years ago, when testing was expensive and its benefits were less understood. This has led to restrictive guidelines.

Costs have now fallen substantially, and there is growing evidence supporting broader criteria for genetic testing. However, guidelines have been slow to change.

This reluctant pace of change also delays reimbursement policy, further restricting patients' access to critical genetic information. Although prices have fallen, the lack of reimbursement remains a barrier for a significant number of patients.

Because of the lack of understanding of the role inherited genetic changes play in influencing cancer incidence, treatment and recurrence, oncologists will soon better understand the importance of hereditary cancer testing.

The need for continuing education

Oncologists need continuing education and updates on early cancer diagnosis and screening for hereditary cancers.

As more studies, such as those on hereditary cancer testing presented at ASCO 2021 this year, are presented and published, and guideline committees meet and assess them, we will see the pace of change accelerate markedly.

Overlooked hereditary testing in colorectal cancer

The colorectal cancer study (abstract 10514), using two independent datasets, evaluated the use of hereditary genetic testing in 55,595 patients. One included both commercially insured people and Medicare Advantage enrollees; the second included patients covered by an insurance company that reimburses hereditary genetic testing for all patients with colorectal cancer.

Very few patients had hereditary genetic testing - 8.1% in the commercial group and 3.8% in the Medicare group.

Of the 788 patients whose results were available for review, 143 (18%) had pathogenic/likely pathogenic genetic changes in genes including MSH2, MLH1, PMS2, MSH6, CHEK2, APC, BRCA2, ATM and MUTYH.

Study author Dr. Sarah Nielsen said, "Of the 30 genes in which changes were identified, 77% were clinically actionable and contained a drug target".

"Thus, 44% of patients could potentially be eligible for precision treatments for Lynch syndrome based on pathogenic variants (changes) in mismatch repair genes, such as PD1 and PD-L1 inhibitors as possible precision therapies" she said.

An additional 25% could be eligible for participation in cancer clinical trials, including studies of PARP inhibitors, and "92% of patients could be eligible for changes in clinical management based on variants detected in genes, according to NCCN or other published management guidelines" she said.

Note: NCCN stands for the US "National Comprehensive Cancer Network." NCCN is an alliance of 31 cancer centers, most of which are designated as comprehensive cancer centers by the National Cancer Institute in the United States. Oncology specialists worldwide most often refer to NCCN guidelines for the treatment of different cancers. 

In a discussion of the paper, Dr. Milan Radovich pointed out that very few requests for hereditary genetic testing were being made despite its coverage under an insurance policy in the United States.

Nevertheless, the results show that 92% of patients whose tumors harbor an inherited genetic change are eligible for changes in their treatment.

A significant proportion of patients with colorectal cancer benefit from hereditary genetic testing, with implications both for treatment decisions and for identifying relatives at risk. Given the frequency of inherited pathogenic mutations in patients with cancer, hereditary genetic testing for the family should be planned alongside genetic counseling.

Hereditary cancer testing in prostate cancer

The prostate cancer study (abstract 10504) included 615 patients, 58% of whom met the NCCN 2019 criteria for hereditary genetic testing. Overall, 72 pathogenic variants were detected in 10.8% of patients; 15% of these variants were in BRCA1/2.

Dr. Colin Pritchard, a faculty member in the Department of Laboratory Medicine and Pathology at the University of Washington, commented that the main message of this study was that some carriers of inherited mutations could be missed if NCCN guidelines were followed.

In a discussion of the paper, he said, "So perhaps we should rethink this, and perhaps simplified testing could be considered. Although it will be quite rare to detect mutations in low-risk disease, we might even consider hereditary genetic testing for all men with prostate cancer to simplify things."