Guidelines exist for identifying patients who should undergo testing to determine if they have a genetic mutation (or variant) that increases their risk for developing breast cancer. But those guidelines were developed at a time when BRCA1/2 mutations were the most widely studied breast cancer susceptibility mutations and others were not as well known.
The landscape has changed, explained Peter D. Beitsch, MD, a breast cancer surgeon at Medical City Dallas Hospital and Research Director for TME/Breast Care Network. So he and his colleagues examined whether current guidelines adequately identify individuals with other genetic mutations (besides BRCA1/2) associated with breast cancer risk who should undergo testing. The results, published online ahead of print in the Journal of Clinical Oncology, showed that current guidelines come up short (2018; doi:10.1200/JCO.18.01631).
Investigators from across the country identified new and previously diagnosed breast cancer patients to undergo genetic testing with an 80-gene panel. A total of 959 patients underwent testing and had their data analyzed for the study. Approximately half met the National Comprehensive Cancer Network's 2017 genetic testing guidelines and the rest did not (and would not have otherwise met the criteria to be tested for a breast cancer susceptibility mutation). The researchers then compared the pathogenic variant rate between the two groups.
The data showed that nearly half of patients with breast cancer with a pathogenic or likely pathogenic variant with clinically actionable and/or management guidelines in development were missed following current guidelines.
"Guidelines restrict appropriate genetic testing and miss almost as many women as they identify with pathogenic variants," Beitsch said of the findings. He added that not all of the identified pathogenic variants (in the 80-gene panel) currently have management guidelines-but Beitsch suspects management protocols will catch up. "As we test more and learn more, I feel confident that we will learn how to manage these patients."
The bottom line is that all patients with breast cancer should have expanded genetic testing to optimize their treatment and identify family members with the same mutation who should be followed more closely, or even have prophylactic surgery to prevent them from getting cancer, Beitsch told Oncology Times.
Here's what else he said about the findings and why the research is so relevant now.
1 What led you and your team to revisit the genetic testing guidelines now and analyze them in this way?
"The guidelines have always seemed arbitrary-a 60-year-old woman with ER-negative cancer should be tested, but if she is 61 she should not. Or if she is 59, but has an ER-positive cancer, then she would not qualify for testing. None of this makes common sense.
"Guidelines were established approximately 20 years ago as a way to pick out women with approximately a 10 percent chance of having a BRCA1 or BRCA2 mutation. That was an era when testing was very labor-intensive and expensive.
"Approximately 5 years ago, a new technique, next-generation sequencing, made testing widely available and significantly cheaper. So, we undertook this study to see if guidelines really mattered-meaning did they really identify most patients with pathogenic variants (the new term for mutation)? They did not."
2 Why do you think there has been such a delay in updating the genetic testing guidelines to better incorporate all these new genetic variants associated with breast cancer?
"The guidelines have been periodically updated (usually yearly) since they were first developed. This, however, [has] just made them incredibly complicated and essentially unusable because of this complexity.
"You qualify for testing if you have breast cancer, have a sister with breast cancer before the age of 50, and a left-handed father with prostate cancer before 63. (I'm kidding [on that last part], but I'm not far off!)"
3 What is the bottom-line message that all practicing oncologists who treat breast cancer should know about these findings? And what should all cancer care providers know?
"[For oncologists who treat patients with breast cancer:] All breast cancer patients have an equal chance of harboring a pathogenic variant whether they meet genetic testing guidelines or not-so test ALL PATIENTS.
"[For other cancer care providers:] All breast cancer patients should have genetic testing with a large panel test to identify patients with pathogenic variants that may not only affect their treatment, but also may be harbored in their unaffected relatives (who should also be tested if the patient has a pathogenic variant)."