When Anne Weber became pregnant with her first child at age 28, little did she suspect that, rather than bringing home a bundle of joy, she would have to contend with a cancer diagnosis that would change the course of her life.

At her first ultrasound, not only did she find out that she had miscarried but also that she had a large cyst on one of her ovaries. That cyst turned out to be cancer.

"Because I didn't have a strong family history of cancer, everyone assumed it would be benign," she recalled in an interview with Medscape Medical News. "We were all very surprised when the pathology report came back with ovarian cancer."

Although the incidental finding may have been heartbreaking, it may also have been lifesaving. Because it was caught early, her ovarian cancer was of stage I. She underwent surgery and is now telling her story, 10 years later.

Weber is now a patient advocate at FORCE (Facing Our Risk of Cancer Empowered), a national nonprofit organization dedicated to individuals affected by hereditary breast, ovarian, and related cancers, andpreviously worked for a while at genetic testing company Myriad Genetics.

How Weber developed ovarian cancer at such a young age was initially a mystery. Without a family history and without symptoms or personal risk factors for it, her physician did not suspect a hereditary cancer even though at the time, National Comprehensive Cancer Network (NCCN) guidelines recommended that physicians consider genetic testing for anyone younger than 50 who are found to have ovarian cancer. However, her physician didn't offer genetic testing, or even counsel her about it.

Weber was left with nagging questions. She wanted to know why she'd gotten ovarian cancer and how she could prevent a recurrence. So she started sleuthing around on the Internet.

"When I was diagnosed, I knew nothing about this. Literally, I didn't know what terms to type into the search engine," she said.

When she stumbled onto an online forum that linked her to the NCCN guidelines, the pieces of the puzzle began fitting together.

This was 2009, and she was living in Atlanta at the time. She asked her physician about genetic testing, and her doctor referred her to the only genetic counselor in the city, who was at Emory University. At that time, the wait time for genetic testing was 6 months.

"Six months when you're dealing with something like cancer can be pretty dire," Anne said.

Genetic testing for breast and ovarian cancer has not always been straightforward, and fast-moving research means that genetic testing is becoming more and more complex all the time.

The NCCN may have recently provided a step in the right direction. On December 4, the NCCN released updated clinical practice guidelines on genetic/familial high-risk assessment for breast and ovarian cancer.

The guidelines represent a fairly radical shift from previous recommendations, which focused on BRCA genes, according to Robert Pilarski, MS, LGC, MSW, LSW, a genetics counselor and professor of clinical internal medicine at Ohio State University's Comprehensive Cancer Center. He was also vice chair of the NCCN guidelines panel that updated the guidelines.

The NCCN recommendations remain anchored in strong, unbiased evidence and reflect a conservative approach regarding genes for which there is lack of evidence, he said. But the guidelines also acknowledge a shift toward panel testing and include a table of 17 moderate- and high-penetrance genes that should be considered in addition to BRCA genes. They also provide management recommendations for people who carry these genes.

"Most people now are doing panel testing where the panel involves multiple genes besides BRCA," Pilarski said, "This guideline update is the closest that we've got to a consensus [regarding breast, ovarian, and pancreatic cancer] because it now specifies a set of genes that are reasonable to include in at least a basic panel."

The use of multigene panels is controversial, as previously reported by Medscape Medical News. A study published in early 2019 in the Journal of Clinical Oncology suggested that roughly half of breast cancer patients who carry a pathogenic or likely pathogenic mutation are missed by current genetic testing guidelines. That study used an 80-gene panel, and the authors recommended expanded panel testing for all patients with breast cancer.

Critics shot back, arguing that universal testing is not warranted and that large, multigene panels may create undue anxiety among patients as well as confusion among physicians. Research is in its infancy for many of these genes, and physicians don't know how or even whether to act on results for some of them. That's especially true for variants of unknown significance, which have not been confirmed to increase risk for disease.

Perhaps in response to this controversy, the NCCN guidelines do not recommend universal testing for breast or ovarian cancer. Instead, they provide clinical scenarios in which genetic testing is clinically indicated, may be considered, or has low probability of clinical utility. The NCCN authors hedge their bets by not endorsing for or against multigene panel testing.

"I think we held back from becoming too definitive because there may be times when other genes are appropriate," Pilarski explained. "We didn't want to lock patients out of insurance coverage, and we didn't want to lock ourselves into a set of genes that could change next week with changing evidence."

This "wishy-washiness" over multigene panels creates a problem for Mehmet Copur, MD, FACP, an oncologist who wrote a critical response to the study published earlier this year. He is affiliated with the Morrison Cancer Center in Hastings, Nebraska, and is an adjunct professor at the University of Nebraska Medical Center in Omaha.

"I believe they have tried to please both parties, and they have been too nice," he said. "My personal opinion is that I would go for high-penetrance genes in clinically suspicious settings. I would ignore that disclaimer note and say, 'I'm going to do this 17-gene panel.' "

Going one step further, he suggested the creation of commercially available gene panels based on the NCCN recommendations for these 17 genes.

"There are a wide variety of panels available with different genes on different panels. There is a lack of consensus among experts regarding which genes should be tested in different clinical scenarios. If possible, it would be helpful to create commercially available gene panels based on the updated NCCN recommendations," he said.

In another major change, the guidelines now include pancreatic cancer for the first time. But in contrast to breast and ovarian cancer, the NCCN recommends that all patients with newly diagnosed pancreatic cancer receive genetic testing.

"Approximately 1 in 20 patients with pancreatic cancer will have an inherited susceptibility gene. Most people with pancreatic cancer who carry these mutations do not have a family history of pancreatic cancer, so you can't rely on family history to guide you about who should get genetic testing," Michael Goggins, MD, MBBCH, who was also involved in updating the NCCN guidelines, told Medscape Medical News. Goggins is director of the Pancreatic Cancer Early Detection Laboratory at Johns Hopkins University School of Medicine, Baltimore, Maryland.

Advantages of genetic testing for pancreatic cancer include guidance regarding choice of chemotherapy and the possibility of cascade testing for prevention or earlier detection of pancreatic cancer in family members.

Other additions to the guidelines include new recommendations for genetic testing for individuals with Ashkenazi Jewish ancestry, as well as new or updated recommendations for Li-Fraumeni syndrome and Cowden/PTEN hamartoma tumor syndrome.

The guidelines also offer an expanded section on genetics risk assessment and genetic counseling. Genetic testing has become increasingly complex, and the NCCN emphasizes the importance of genetic counseling throughout the testing process.

It has been 10 years since Anne Weber was diagnosed with ovarian cancer. Because she was diagnosed at a young age (28 years) and her other ovary was unaffected, she opted for surgery to remove only the ovary with the tumor.

After her own Internet research and at her own request, Weber underwent genetic testing. She found out that she is a carrier of the BRCA2 mutation, which carries high risk for breast, ovarian, and pancreatic cancer.

Current recommendations are that people with BRCA2 mutations start breast cancer screening at age 25, so Weber was screened immediately.

Her first breast MRI revealed a mass that was found to be stage I breast cancer. At that point, she chose to have her other ovary removed, as well as both fallopian tubes and both breasts, which significantly reduces her risk for recurrence.

"I'm so incredibly grateful that I found the information. All the guidelines say that I shouldn't even have had my first mammogram at my current age of 39. So there is low likelihood that I would have been diagnosed by now, and it certainly would not have been stage I," she said.

Since her diagnosis, she and her husband have adopted a child.

"Genetic testing isn't right for everyone. People aren't going to make the same decisions I did," she said. "The biggest thing is to understand that being positive doesn't mean that you're going to get cancer. It just allows you to have that circle of care to try to prevent cancer, or at least catch it earlier, when it's more treatable."

NCCN. Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Version 1.2020. Full text

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Heartbreaking News, Then Tumor Find Leads to Genetic Testing - Medscape