Cancer is caused at the molecular level by a large variety of genetic alterations that modify cell behaviors, making it a highly diverse disease. While the majority of the genetic alterations that give rise to or contribute to the development of cancer are due to chance, approximately 5% to 10% of these genetic alterations are inherited. Increasingly, genetic testing plays an important role in both detection and treatment.
Breast cancer is the most common cancer in women that carries a significant chance for loss of life. With the discovery and identification of the genes BRCA1 and BRCA2, genetic tests were developed to identify patients and family members who harbor mutations in these genes making them more susceptible to breast cancer.
However, many families with a high number of breast cancers do not have detectable mutations in these two genes. This suggests that there are additional breast cancer susceptibility genes contributing to these familial clusters of disease.
What is panel testing?
In the past, genetic testing for inherited susceptibility to cancer usually involved testing for just one or two genes. However, new advances in genetic testing technologies have led to the ability to provide simultaneous testing of several genes with reduced cost and turnaround time. These tests are collectively called “panel” tests. Panel testing is now clinically available that evaluate – at the same time – 15-60 genes potentially involved in cancer susceptibility.
Panel testing represents major progress in understanding our genes, but the use of panel testing hasn’t been widespread. In the United States, this is because most insurance companies consider the panel tests investigational, and will not cover the cost of testing, and clinical management guidelines for mutation carriers of many of the tested genes are not yet available. Nonetheless, some patients have opted to proceed with testing after counseling that panel testing is the best available option for them based on their family history of cancer.
Proceeding with genetic testing can produce one of three results:
- Positive: A gene change, or mutation, that is associated with an increased cancer risk has been found which may help explain the family history of cancer.
- Negative: No mutation is identified in any of the genes tested. However, a negative test result does not eliminate the cancer risk based on family history of cancer.
- Variant of uncertain significance: A gene change that may or may not be associated with an increased risk for developing cancer is identified. There isn’t yet enough information to determine whether this variant is associated with an increased cancer risk.
The knowledge we gain of a patient’s inherited susceptibility to breast cancer can help plan current and future clinical management. Patients who are at increased risk can:
- consider increased surveillance (mammogram and breast MRI yearly, professional breast exam every six months), etc.
- consider taking medications (tamoxifen, raloxifene, exemestane) to reduce the risk of developing breast cancer
- consider prophylactic (preventative) removal of the ovaries after childbearing and/or prophylactic bilateral mastectomy
- clarify familial cancer risks, based on gene-specific cancer associations
- offer treatment guidance (for example, avoidance of radiation-based treatment methods for individuals with a TP53 mutation).
- identify other family members at risk
- consider pre-implantation diagnosis
- perhaps in the future, provide customized, gene-specific, treatment
There has been significant progress in broadening the clinical testing of cancer-related genes. This new technology will increase the discovery of new susceptibility gene mutations for breast and other cancers. Knowing that a person carries a genetic mutation may lead to customized, targeted therapies for both treatment as well as precision management for prevention, which is the real meaning of “personalized medicine.”
However, this new technology still needs to be treated with caution. Genetic counseling for some of these genes can be difficult due to very little information available about the risks they confer.
Further research and genetic testing in large series of patients and their families will help determine the risk of developing cancer. Most importantly, we believe that an investment in a national database to make outcomes of individuals who undergo panel testing would be crucial to understand both outcomes and efficacy of prevention and treatment modalities.
The Breast and Ovarian Cancer Risk Evaluation Clinic at the U-M Comprehensive Cancer Center provides an accurate assessment of personal risk for developing breast and other related cancers, education regarding availability of genetic testing and current research programs, and a plan for follow-up and preventive care.
The University of Michigan Comprehensive Cancer Center’s 1,000 doctors, nurses, care givers and researchers are united by one thought: to deliver the highest quality, compassionate care while working to conquer cancer through innovation and collaboration. The center is among the top-ranked national cancer programs, and #1 in Michigan for cancer patient care. Seventeen multidisciplinary clinics offer one-stop access to teams of specialists for personalized treatment plans, part of the ideal patient care experience. Patients also benefit through access to promising new cancer therapies.