Mutations in breast cancer genes go undetected in certain breast cancer patients, study finds

Findings make a case for universal genetic testing of breast cancer patients

A significant number of women are missing out on a test to detect potentially harmful mutations in their breast cancer genes, because of limits on the types of patients who are eligible for testing, a recent study has concluded.

According to Dr. William Foulkes (Senior Investigator and Head of the Cancer Genetics Laboratory of the Lady Davis Institute for Medical Research at the JGH), the study set out to determine what would happen if all women with a first diagnosis of invasive breast cancer were tested for the presence of genetic mutations that are associated with an elevated risk for breast cancer.

It found that mutations—also known as pathogenic variances—exist in more women than those who now qualify for testing on the basis of age, family history and other factors, says Dr. Foulkes, Director of Medical Genetics at the JGH and the MUHC. He is also the Distinguished James McGill Professor in McGill University’s Departments of Medicine, Oncology, and Human Genetics.

Dr. Foulkes explains that genetic testing is of great value, since it aids in assessing not only the risk for a recurrence of breast cancer, but the associated risk for ovarian cancer. Given the strong link between the two types of cancer, early information about mutations in breast cancer genes can be useful in attempting to prevent ovarian cancer.

In addition, he says, since genetic testing helps to identify the risk of breast cancer in the relatives of the breast cancer patient, the patient and her family would be referred for genetic counselling if mutations in the genes are discovered.

The study examined 729 women over the age of 18 who had had an initial diagnosis of invasive (but not metastatic) breast cancer during the previous six months.

Some of them would automatically have been eligible for genetic testing, since they met the current criteria. However, for the purposes of this study, all of the women were sent for genetic testing.

The research determined that among women with mutations in the three most important breast cancer susceptibility genes, about one-third would not normally have qualified for testing.

The findings, published in JAMA Network Open, were made possible through the collaboration of a team at the Lady Davis Institute that included Principal Investigator Stephanie Wong and Associate Researcher George Chong. The study was funded by the JGH Foundation and the Quebec Breast Cancer Foundation.

Ideally, Dr. Foulkes says, universal genetic testing should be routine. Unfortunately, the test is expensive, and this means the costs must be considered along with the benefits.

“It’s simply impossible for a counsellor to see many more people and still provide appropriate one-to-one attention,” Dr. Foulkes says. “During their sessions, patients always have follow-up questions that need time to be fully answered. It’s not just a matter of going in for a quick conversation.”

However, the high cost doesn’t mean it is justifiable to bypass certain women with breast cancer who need genetic testing, Dr. Foulkes says. If anything, he continues, the study highlights the need to find a way to perform the test more inexpensively, and possibly even to use artificial intelligence to increase the number of patients who can be seen by genetic counsellors.

“Conducting this study was our way of trying to kick-start the process of universal testing by going ahead and seeing what would happen,” he says. “I think this has helped to sensitize treating physicians and patients to the whole process of genetic testing, and how making it universally available could be possible.”