Advances in genetic testing are leading to highly targeted treatments — and a healthier future for millions.
Tuya Pal, M.D., FACMG
American College of Medical Genetics and Genomics (ACMG) and Professor of Medicine, Vanderbilt University Medical Center
About 13 percent of all women in the United States will be diagnosed with breast cancer at some point in their life, and it remains the second deadliest form of cancer in women. But a cancer diagnosis doesn’t just affect the patient — it affects their family, caregivers, and loved ones. That makes genetic testing crucially important.
“Knowing about inherited cancer can change the course of a family,” says Tuya Pal, M.D., FACMG, of the American College of Medical Genetics and Genomics (ACMG) and professor of medicine at Vanderbilt University Medical Center. “It can save lives because we can diagnose cancers early or prevent them altogether.”
Advances in genetic testing
For years, genetic testing was incredibly expensive and so had to be used very specifically — this was partly because the two most important genes for inherited breast cancer, BRCA1 and BRCA2 were patented. That meant only a single lab in the United States could test for those genes.
But the last few years have seen incredible advances in genetic testing for cancer. “In 2012 we got access to next-generation sequencing technology, which enabled us to test for multiple genes all at the same time at a really low cost,” Dr. Pal explains. “And then in 2013, the patent for the BRCA genes fell. So, you could include the BRCA genes on these panels.”
Research continues to change how we approach cancer treatment. Today, tumor sequencing has become more affordable, which means labs can drill down into the DNA code of tumors to guide treatments. And Dr. Pal is one of the lead authors of a recent paper published by the American College of Medical Genetics and Genomics detailing the discovery of a new gene mutation related to breast cancer, PALB2 (partner and localizer of BRCA2).
“PALB2, at this point in time, is in many of our minds the third-most important gene for breast cancer,” notes Dr. Pal. “Compared to BRCA1 and BRCA2, PALB2 has lower cancer risk. But what’s concerning in PALB2 is that some studies have suggested if you have a PALB2 mutation, your cancers could be more aggressive. However, this is not yet proven and more studies are still needed to figure this out.”
The good news is that more information leads to more targeted treatments. “PALB2 is very much integrated in the BRCA1 and BRCA2 molecular pathway — as reflected in its name, it partners with BRCA2,” explains Dr. Pal. “There’s very promising emerging data that the targeted treatments that we use for BRCA1 and BRCA2 may also work for PALB2.”
Taking control
Dr. Pal points out that one factor limiting the impact of genetic testing is the estimate that only about 20 percent of adults who carry inherited cancer gene mutations like BRCA have been identified. This is further complicated by disparities in awareness and access to genetic testing based on socioeconomic status and race, as well as gaps in insurance coverage for these genetic tests.
These gaps exist despite the compelling evidence of the benefits of genetic testing for inherited cancers, including breast and other cancers. “A genetic mutation like BRCA1, BRCA2, or PALB2 helps guide therapy, but it can also guide cancer risk management,” notes Dr. Pal. “It can guide risk for a second breast cancer, or risk for ovarian cancer. And sharing this information with family members has great potential to identify individuals that are the highest risk of having an inherited cancer gene mutation.”
Dr. Pal sees a future where cancer is a lot less frightening. “We’re not going to eliminate cancer,” she notes, “because cancer is essentially cells growing out of control. It’s mutations that occur in our cells, and being human means we are going to acquire mutations over the course of our lives. Our hope is that cancer someday will become a chronic disease, like diabetes — if we know how to target the cells to stop them from growing, we may be able to better treat it.”