A paradigm shift away from “one-size-fits-all” treatment in cancer has fueled the movement toward precision medicine, an approach to cancer treatment that ensures delivery of the right intervention to the right patient at the right time.
Compared with 20 or 30 years ago when chemotherapy was the standard of care, targeted therapies are now actually personalized to a patient, thanks in large part to genetic and genomic profiling. At the AONN+ 2019 Midyear Conference, Sherri Millis, PhD, MS, and Frank dela Rama, RN, MS, AOCNS, AGN-BC, reviewed the basics of precision medicine and offered insight into how navigators can incorporate genetics (related to a person’s inherited genes) and genomics (related to cancer-specific mutations) into their day-to-day practice.
“As we try to identify what is specifically driving a patient’s cancer, we can then identify the therapy that is going to be most effective,” said Dr Millis, Senior Manager of Clinical Collaborations at Foundation Medicine. “Rather than treating every patient as if they are identical, we can now treat the unique disease within a patient’s cancer.”
Germline vs Somatic: What’s the Difference?
A germline mutation is an inherited change in a gene that causes an increased risk for cancer. Cancers arising from these germline mutations (also called hereditary cancers) make up 5% to 10% of all malignancies.
According to Dr Millis and Mr dela Rama, a Prostate Cancer Nurse Navigator, Clinical Nurse Specialist, Oncology/Genomics, Palo Alto Medical Foundation, CA, it can be helpful to consider germline genetic mutation information as a biomarker, similar to EGFR in lung cancer or HER2 testing in breast cancer, but capable of providing information regarding future cancer risk (not only for the patient being tested, but also for their family members).
But most cancers have somatic mutations: a change in a gene that occurs over the course of a person’s life that can lead to the development of cancer.
“We have the germline community, and we have the somatic community, and we’re slowly understanding that there are differences, but there are also commonalities,” said Dr Millis. Ten years ago, 2 completely different databases tracked inherited DNA variants and somatic DNA alterations. “But now we go through both databases…to try and extrapolate more information about someone’s cancer,” she added.
The “marriage” between these 2 types of testing is helping to further inform treatment options, and the results can now be used to predict whether patients will respond to certain therapies.
Using Tests to Guide Therapy
In a woman with ovarian cancer, it is crucial to understand all of the ways her cancer might have developed, said Dr Millis. One in 4 women with ovarian cancer are BRCA positive, but whereas those mutations were previously assumed to be inherited, it is now understood that about 50% of those women have a somatic mutation.
To get more of these patients on therapy sooner, all patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer should be referred for genetic counseling and testing. “And they are likely good candidates for testing of the tumor itself in the absence of a genetic reason for the disease,” she noted. “If we just do genetic testing, we’re going to miss some patients, because in the normal blood we’re not going to find a BRCA 1/2 alteration that is just in the tumor.”
DNA variants such as BRCA1 and BRCA2 are now being identified as likely drivers in other cancers—with a lower penetrance than is seen in the well-known breast and ovarian cancer arenas—but irrespective of germline or somatic origin, she added.
In newly diagnosed men with low- to intermediate- risk prostate cancer, somatic tissue genomic testing can now identify which patients are appropriate for active surveillance compared with immediate treatment. Knowing this Genomic Prostate Score can help to facilitate shared decision-making between patients and navigators, added Mr dela Rama. Men with intermediate- or higher-risk prostate cancer may consider germline genetic testing if they have advanced/metastatic disease, a family history of specific cancers, or a known mutation in the family.
Next-generation sequencing (NGS) represents a major step forward for both germline and somatic testing. NGS has the ability to analyze multiple genes or DNA fragments simultaneously, quickly, and cost-effectively. But according to Dr Millis, the raw data that come out of NGS can be difficult to interpret and can vary depending on who is reading the results.
“The important thing is understanding the differences between the tests that are offered, and that can take a lot of evaluation and education,” she said. “Being able to generate a report that has really good analytically validated—and hopefully clinically validated—information is going to give us better information for our patients, especially for these larger panels.”
Beware of caveats with popular direct-to-consumer testing kits (such as 23andMe), they added. These are not yet clinically valid, nor are they comprehensive, but if the test identifies something of potential concern to a patient, they should be recommended for confirmatory testing.
As genetic and genomic testing continues to expand, patients will continue to take a more active role in cancer prevention and treatment. Navigators should be prepared to educate their patients, counsel them on the pros and cons of the options available, manage expectations, and coordinate their care in precision medicine.
“Keep listening to your patients,” added Dr Millis, “and then help guide them on where they need to go.”