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When Katy Mathes and six of her family members learned they had a mutation on a BRCA gene that significantly raised their risk of breast cancer they underwent major surgery. But years later, the genetic testing company lowered the family's odds of getting the disease, Amy Dockser Marcus reports for the Wall Street Journal.

In August 2015, Mathes decided to get a BRCA test. Mathes' mother had been diagnosed with breast cancer at 49, and four of her aunts had tested positive for the BRCA gene, and "moved quickly to get surgery," Dockser Marcus reports.

Mathes and her sister, Tricia Leigh, also had positive tests. The test results showed that Mathes had up to an 84% risk of developing breast cancer by age 70 and up to a 27% risk of developing ovarian cancer by age 70. Among the general population, the odds of developing breast or ovarian cancer are 7.3% and 0.7%, respectively, Dockser Marcus reports.

But the two women grappled over the decision of whether to get surgery: Mathes wanted another child and her sister was breastfeeding her second child.

After consulting with additional doctors, Mathes eventually decided to have her ovaries and fallopian tubes removed, the same procedure her aunts, sister, and mother underwent. In addition, Mathes and her sister had double mastectomies.

"I treated my test results like the Bible," Mathes said. "There was no questioning the report."

But years after the initial test, Myriad Genetics, the molecular diagnostics company that did Mathes' test as well as her relatives', changed its classification of the BRCA variant Mathes has from "pathogenic" to "unknown significance," a move that Myriad said is very unusual.

By this point, Mathes and six of her family members had undergone surgery based on their test results. When the sisters learned the news, Mathes said, "My brain just shut off."

Susan Manley, SVP of medical services at Myriad and a board-certified genetic counselor, said, "We know these are very difficult situations. We make these reclassifications very carefully. The science is evolving." She added that changing a classification from harmful to uncertain "is a rare event, but I understand that rare is of no consolation to the patient when it happens to them."

BRCA tests are among the most common genetic tests in existence, Dockser Marcus writes, and genetic testing guidelines have expanded who should receive BRCA tests. Major genetic testing companies such as 23andMe, Ancestry, and MyHeritage now offer the tests for BRCA1 and BRCA2 genes.

However, not every lab agrees on the specific classification of a BRCA gene variant, Dockser Marcus reports. That's in part because there are "tens of thousands of BRCA variants" and not all of them necessarily carry the same level of risk for a patient, Dockser Marcus reports.

Fergus Couch, a professor at the Mayo Clinic, said some variants "have intermediate or moderate levels of risk, not full-blown risk." For a number of those variants, labs "are making a judgment call but that is not always clear to the public," Couch said.

Stephen Chanock, a geneticist at the National Cancer Institute, said, "[G]enetics is murky." He added, "It's not so simple as 'Doctor, do I have to worry or don't I have to worry?'"

According to Melissa Cline, a researcher at the University of California Santa Cruz Genomics Institute, and project manager of the BRCA Exchange, the analysis on the BRCA variant in the Mathes' family put a lot of weight on a 2011 paper that found the variant likely alters the BRCA2 protein, which can help suppress tumors.

Seth Marcus, a genetic counselor at Advocate Health Care who counseled Mathes' mother and one of her aunts, said he checked a public database to see how other labs classify the variant once he heard of Myriad's change. He said six labs still classify the variant as "likely pathogenic."

"In the end, you give the patient the data and the knowledge you know," he said.

Dockser Marcus reports that Myriad currently has 38 people in its database with the BRCA variant Mathes and her relatives have, 12 of whom come from Mathes' family. Mathes said that if she had known about the sample size, she and her husband may have asked more questions about whether surgery was appropriate.

Now, based on Mathes' family history and Myriad's classification change, Mathes' genetic counselor estimated her lifetime risk of developing breast cancer is 21%, Dockser Marcus writes.

"That is not high enough to make me remove organs," Mathes said. "I would have had another kid. I would have waited to do surgery" (Dockser Marcus, Wall Street Journal, 12/20/19).

Continue reading here:
'I would have had another kid': How an imperfect gene test led to major surgeryand big regrets - The Daily Briefing

This entry was posted on January 8, 2020 at 11:43 pm and is filed under Molecular Genetics. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |