12 minute read
Genetic Testing for Hereditary Cancers with Primary Providers
Reveals Opportunities to Prevent and Manage Cancer Risk
Doctors have long known that inherited gene mutations can significantly increase a patient’s lifetime risk for developing cancer. Since prevention is the first line of defense, the US Preventative Services Task Force recommends that primary care physicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer. The American College of Obstetrics and Gynecology’s Committee on Genetics makes essentially the same recommendation: “A hereditary cancer risk assessment is key to identifying patients and families who may be at increased risk of developing certain types of cancer. This assessment should be performed by obstetrician–gynecologists or other gynecologic care providers and should be updated regularly."
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While testing for genetic mutations used to be either nonexistent and/or cost prohibitive, advances in genetic research now make it easier to identify and understand how these mutations correlate to other cancer syndromes. Since 2014, insurance companies have been required to cover all costs, including out of pocket, for genetic counseling and BRCA testing to patients who meet certain personal or family history criteria.
Medicare, however, still only pays for patients who already have been diagnosed with cancer. “It’s more cost-effective to prevent cancer than to treat it,” notes Sarah Geno, a physician assistant at Rochester Clinical Research who consults with physician practices on risk assessment and genetic testing and shares best practices for implementing hereditary cancer screening programs. She understands how critical this information is in providing optimal medical management based on patients' individual risk; having worked with genetic laboratories, Geno finds Natera accessible, affordable, and easy to integrate into a practice’s existing screening program. Earlier this year, the Breast Cancer Research Foundation published the results of a large, multi-center study in the NEJM. Lead investigator, Fergus Couch, PhD, a pathologist at the Mayo Clinic, wanted to improve the accuracy of breast cancer risk assessment for women without a family history. "While the risk of developing breast cancer is generally lower for women without a family history, this study showed that 30 to 50 percent of breast cancer mutations occur in women who have traditionally not been considered high risk.” Because of this, Geno adds, “Natera offers a low cash price for these patients and a sliding scale for patients whose need meets financial guidelines. This level of support for my patients was an important part of choosing Natera’s testing lab.”
American College of Obstetricians and Gynecologists practice bulletin 182 2017 (reaffirmed 2019)
Well known for Panorama, the top NIPT in the US, and its combination NIPT/Carrier Screen kit, Natera also offers Empower, developed in partnership with Baylor Genetics, which analyzes genes associated with an increased risk for hereditary cancers. Geno considers Natera’s laboratories “the most accurate” in detecting genetic abnormalities.
Natera’s full multi-cancer panel expands up to 53 genes and test results include National Comprehensive Cancer Network (NCCN) guidelines for recommended medical management changes to mitigate risk.
For tests that produce “variants of uncertain significance” (VUS), Natera-developed RNA testing delivers another layer of functional evidence that may move a variant into the positive or negative category. Using a single tube of patient blood, Empower with RNA improves detection and classification of some variants that may fall within splice site regions and automatically provides an updated report within two weeks, reclassifying the variant if RNA analysis produces a different result.
Natera’s comprehensive breast cancer risk assessment uses the Tyrer-Cuzick evaluation, recommended for patients who may have an increased cancer risk even without a gene mutation. This risk may involve the family’s cancer history and the patient’s own estrogen exposure throughout her lifetime. “This looks at all the other risk factors that may be there, like age of menses, how many births, hormonal exposures, smoking, tissue density, premenopausal, or postmenopausal,” said Geno. If Tyrer-Cuzick shows a risk of >=20%, the patient is eligible for a breast MRI in addition to a mammogram and two clinical breast exams per year—all covered by insurance.
Who is eligible, and why
Genetic testing can be used with patients who have a family history of cancer to prevent disease before it develops—but according to research published in Genetics in Medicine in 2015, up to 80 percent of women at high risk for hereditary breast or ovarian cancer have never been tested, or even discussed testing with their health care providers. Among patients at risk for Lynch syndrome, as many as 69 percent told researchers they were never advised to seek genetic screening by their providers.
it’s considered standard of care,” said Geno.
“You want the best care for your patients…but you also want to be sure that you are not delaying care. If this information is not acted on and a patient is later diagnosed with a cancer, the provider is opening themselves up for litigation.”
Victor Cotton, MD, Esq.
“I’ve been in the medical legal field for over 20 years, and this is the greatest malpractice threat I’ve ever seen. Fortunately, it is also the most readily solvable. All it requires is for us to take a family history, recommend genetic testing to those patients who meet criteria, and document our efforts,” says Victor Cotton, MD, Esq.
Using the BRCA gene as an example, we know that approximately 1/400 women possesses a pathogenic BRCA mutation. In the US, that equates to about 500,000 women. Each woman faces a lifetime risk of breast cancer of up to 85% and a risk of ovarian cancer of up to 60%. Because of the near certainly that these patients will develop cancer, numerous entities, including the American College of Obstetrics and Gynecology and the US Preventive Services Task Force, have issued recommendations for identifying these women, including screening when the patient’s family history is reviewed. If positive for certain patterns of cancer, genetic testing should be recommended; and, if the patient tests positive for a pathogenic mutation, medical and surgical options for reducing cancer risk should be explored. “In terms of impacting these patients’ lives in a positive way, this is enormously beneficial. We’re able to prevent cancers that are almost certain to occur.” While any individual may develop cancer in their lifetime, inheriting a gene mutation can increase the risk by 30 to 50 percent—and some genes increase the risk to as much as 90 percent.
Statistics show that 1 in 4 patients meet medical
guidelines for hereditary cancer testing with
Although accepted guidelines and recommendations have been out for almost 10 years, only about 15 percent of patients who meet criteria have been tested, which means that most women who harbor a pathogenic mutation have not been identified.
Inforrmed Care
Patients with an increased risk may be eligible for earlier, more frequent screenings and recommended for screenings with different modalities. Family members need this information so they can be appropriately managed according to their individual risk. Preventative care may include regular blood tests; imaging, including CT or MRI scans; or in high-risk cases, surgery to prevent a cancer diagnosis. This is particularly important in younger women with a family history of breast and/or uterine cancer who have not yet started their own families. “Through genetic testing I have helped many patients mitigate their risk,” said Geno. “Patients with mutations putting them at higher risk for HBOC or Lynch syndrome were able to make informed decisions relative to their ongoing healthcare. When they have testing and know the results, they can get the family counseling they need. For instance, if they are at a high risk for uterine, breast or ovarian cancer, they may decide to put family before career, or maybe they will decide that childbearing is not for them and opt to remove their ovaries, uterus, or get a double mastectomy. For women in their 30s, if they know they have a 50 percent chance of developing cancer, they can take action.”
Taking steps to prevent cancer does not necessarily require major surgery, she added, citing holistic approaches and things like oral contraception, which reduces the risk of ovarian cancer. “Having the knowledge and the diagnosis, they can get treatment to prevent the cancer from ever being there.”
Understanding a woman’s hereditary cancer risk can dramatically affect medical management to prevent or delay cancer occurrence and inform cancer treatment.
The Patient Experience
In her years at three different medical practices in the Rochester, New York area, Alisa Lukas, MSN, APRN, Women’s Health Practitioner- BC, provided genetic cancer screening to as many as 1,000 patients.
When COVID hit, however, risk screening was “put on hold,” so Lucas began regularly screening patients for genetic cancer risk at the Canandaigua Medical Group OBGYN where she worked. “I screened two to three patients a day for genetic cancer risk.”
Sarah Geno, PA
In addition to her routine nurse practitioner duties, Lukas used appointment slots to explain to patients what the screening could reveal about their genetic predisposition to cancers. Lukas noted that 95 percent of her patients chose to have their blood drawn on the spot. “I saw patients as young as their early 20s, whose mothers had had ovarian and breast cancer,” she said. “I also had patients in their late 80s who wanted to be screened—not just for themselves, but for their family members.”
She would always emphasize that “only 10 percent of cancers are genetic—the other 90 percent just happen. But if we know someone has a particular gene associated with a specific cancer, we can do closer surveillance for early detection of the cancer for better survival.”
Lukas reviewed detailed lab results with patients and offered referrals to appropriate cancer centers, oncologists or diagnostic facilities for those with positive gene mutations. Results also were documented within the patient’s electronic health record.
Genetic cancer risk screenings also assist surgeons evaluating patients for gynecological procedures such as hysterectomies. “If providers referred patients to me for genetic cancer screening testing preoperatively, and results showed they had a positive gene mutation for ovarian cancer, the OB/GYN surgeon would likely remove the ovaries—and if they did not have that positive gene, the surgeon might leave the ovaries
intact rather than put some of their premenopausal patients into early menopause.” Lucas explained.
Power of Knowing
Although the testing procedure is simple and relatively painless, some patients still resist the opportunity to find out about their genetic risk for cancer.
“Some people fear positive results,” said Lukas. “It's all about how the information is presented to the patient. If they understand that, as their provider, you need that information to determine appropriate screenings and surgeries going forward, they will see the importance in stratifying their risk.”
Higher-risk patients can start early detection screenings and can inform family members interested in preventative care. Patients at risk for certain hereditary cancer syndromes can be referred to specialists who will follow them for those increased risks.
“These are all measures we can implement to improve patient outcomes,” said Geno. “Isn't that what we want as providers—to do our best for our patients?”
The greater objection, however, has to do with cost. Many health insurers cover genetic testing for people with one or more risk factors: family history, previous diagnosis of cancer, or specific ethnicity with a higher incidence of a particular cancer (women of Ashkenazi Jewish descent are at greater risk for breast cancer, for example). Lukas and Geno both noted that their decision to go with Natera tests had to do, in part, with the company’s work with insurance companies to make sure that patients’ screening tests would be covered.
“I always told patients that they would be notified prior to the test being performed at the laboratory if they were not fully covered by their insurance, so they could decide if they wanted to cover the additional cost or decline testing,” said Lukas. “Natera does a good job getting the genetic cancer screening test covered.”
Getting Started with Genetic Testing
“The lab I use works with offices from start to finish. They make patient identification, test ordering, billing and followup care easy and helped us seamlessly incorporate it into our
current workflow. They also offer free genetic information sessions for patients and providers,” says Geno.
Patients whose healthcare providers don’t actively screen and/or test can utilize a free screening and eligibility program offered through Rochester Clinical Research at www.rcrclinical.com/hereditary-cancer-screening/ “Most of the time it’s covered by insurance,” Geno notes.
While many practices now see the value in offering genetic cancer risk testing to patients, others still require education about the benefits testing can provide to all patients at risk for cancer. Education is key to making this testing a norm throughout OB/GYN practices. “My goal is to educate family nurse practitioners, undergraduate nursing students, and physician assistant students about genetic cancer risk screening,” Lucas said. “It’s important that we incorporate this into the curriculum, so future providers know what can be done and how it can benefit patients. Genetic cancer risk screening is a powerful tool to detect cancer in early stages, giving patients a better chance at survival.”
Hereditary cancer testing simplified
Designed with your practice in mind
Empower panels include genes associated with increased risk of common hereditary cancers, with options to suit your preferred screening strategy.
Breast Ovarian Uterine Colorectal Gastric Prostate Pancreatic Melanoma
PANEL PANEL PANEL PANEL
BRCA1 & BRCA2 GYN guidelines-based Multi-cancer* Multi-cancer expanded
2total genes 19 40 53total genes total genes total genes
BRCA1 & BRCA2 Breast, Ovarian, Endometrial cancers and Lynch Syndrome genes Most commonly screened-for hereditary cancer genes across 8 cancer types Includes multi-cancer panel plus additional genes with emerging evidence of elevated cancer risks
Genes
BRCA1, BRCA2 + Additional Genes ATM, BRIP1, CDH1, + Additional Genes APC, AXIN2, BAP1, BARD1, + CHEK2, EPCAM, MLH1, BMPR1A, CDK4, CDKN2A, MSH2, MSH6, NBN, NF1, GALNT12, GREM1, HOXB13, PALB2, PMS2, PTEN, MEN1, MITF, MSH3, MUTYH, RAD51C, RAD51D, NTHL1, POLD1, POLE, STK11, TP53 RNF43, RPS20, SMAD4, VHL
Additional Genes
CTNNA1, DICER1, KIT, MRE11, PDGFRA, RAD50, SDHA, SDHB, SDHC, SDHD, SMARCA4, TSC1, TSC2
