Genetic testing brings treatment opportunities and confusion for breast cancer patients – Daily Montanan

The past decade has seen a rapid expansion of genetic testing, including new devices to inform patients diagnosed with breast cancer of their risk of recurrence and guide treatment.

But the clinical significance of many of the genetic mutations currently identified remains unclear, leaving experts wondering when and how to introduce all the new tests available. Patients may end up paying out-of-pocket for tests that are not yet standard of care, and even modern oncologists are unsure how to incorporate the flood of new information into previously standard treatment protocols. You may not know. .

A quarter century ago, Myriad Genetics ushered in a new era of genetic testing by introducing the first breast cancer genetic test for BRCA mutations, two genes associated with a significantly increased risk of breast cancer. I did. BRCA1 and BRCA2 mutations account for half of all hereditary breast cancers, and people with problematic mutations in either of these genes have a 45% to 72% chance of developing breast cancer during their lifetime. They may also be at higher risk for ovarian cancer and other cancers than people who don't have harmful BRCA mutations.

However, the clinical significance of many other genetic tests is more ambiguous.

Testing for the BRCA1 and BRCA2 genes used to cost thousands of dollars. Now, at a fraction of the cost, doctors can order multigene testing panels from commercial laboratories that examine mutations in dozens of genes. Some direct-to-consumer companies offer screening panels for hundreds of dollars, but their reliability varies.

When Jen Carberry was diagnosed with breast cancer in 2017 at the age of 44, genetic testing identified a mutation in a gene called PALB2 that significantly increases the risk of developing breast cancer. Guidelines recommend that breast cancer patients with PALB2 mutations, as well as those with BRCA1 and BRCA2 mutations, consider undergoing mastectomy to reduce the chance of breast cancer recurrence.

“I wish genetic testing was the standard of care,” Carberly said. My insurance company covered the cost, so I didn't have to pay for the test.

Carberly, who lives in Sterling Heights, Michigan, said the test results confirm her already-made decision to undergo a double mastectomy and provide important information for her family, which includes her 21-year-old daughter and 18-year-old son. He said he did. People are likely to be tested in their mid-20s or early 30s.

But some breast cancer experts say widespread testing may also identify genetic mutations with unclear effects, raising concerns, leading to further testing and treatments of questionable value, and costing the health care system money. I am concerned that it may rise.

It can also be confusing to patients.

“It's common for patients to come to us after getting confusing results elsewhere,” he said. Dr Mark RobsonDirector of Breast Services at Memorial Sloan Kettering Cancer Center in New York City. Robson said the cancer center has a clinical genetics service staffed by physicians and genetic counselors who can help people make decisions about how to manage their genetic test results.

For people diagnosed with breast cancer, many expert groups, including the influential National Comprehensive Cancer Network (NCCN), Recommend limiting testing Certain people, including those with high-risk factors such as a family history of breast cancer. People who are under 45 years old at the time of diagnosis. People with Ashkenazi Jewish ancestry.

But in 2019, the American College of Breast Surgeons recommended a different approach. Offer genetic testing to all patients People who have been diagnosed with breast cancer or have a history of breast cancer. This recommendation was controversial.

“The NCCN guidelines cover most women who need testing, but we wanted everyone to get tested.” Dr. Eric Manahana general surgeon in Dalton, Georgia, and a member of the Surgeons Group's board of directors.

Mutations in other genes associated with breast cancer are much less common than BRCA1 and BRCA2 mutations and generally do not increase the risk of developing breast cancer as much. The carcinogenic impact of these genes may not be as clear as that of the BRCA genes, which have been tested since the mid-1990s.

And it's often unclear whether the appropriate response to less common mutations is whether to consider risk-reducing mastectomy or increased screening.

“As you look at other genes, things get sloppier and sloppier,” he said. Dr. Steven Katzprofessor of medicine and health management and policy at the University of Michigan. “The risks for various cancers tend to be lower, but they are less certain and more variable. You might walk away wondering, 'Why did I need to know that?' yeah. ”

After you are diagnosed with breast cancer, genetic testing can help determine what surgery to perform. For example, some people may choose a more extensive surgery, such as a double surgery, if they are at high risk of recurrence or if a new breast cancer develops. Mastectomy. Testing can also provide important information to families about their potential cancer risk.

(This type of “germline” genetic testing, so-called “germline” genetic testing, looks for mutations in genes inherited from both parents. This is a genomic tumor test that looks for mutations in genes inherited from both parents.) Unlike tests, it helps doctors understand (for example, how fast cancer cells are dividing and the likelihood of cancer recurrence).

Germline genetic testing is also increasingly helping determine other treatments. Some metastatic breast cancer patients with BRCA1 or BRCA2 mutations may be good candidates for PARP inhibitors, anticancer drugs that target tumors with mutations in these genes.

But genetic tests that reveal genetic variations in many other genes provide actionable information that is less clear, even if a positive result makes people nervous.

At Memorial Sloan Kettering, cancer experts are focused on “feasibility of treatment,” Robson said. Will the test help decide whether someone should have a double mastectomy or provide other important guidance?

“A policy of testing everyone would identify fewer additional BRCA breast mutations, but it would be costly,” he said.

As a result, doctors are debating the best way to deploy and incorporate new genetic knowledge. Insurance companies are considering who should pay claims.

There is both underuse of tests that science claims are relevant and overuse of tests that experts claim provide information that cannot be interpreted with scientific certainty.

As a result, newly diagnosed breast cancer patients face potentially confusing costs for genetic testing and, in some cases, little guidance about appropriate treatment.

Some doctors say the first step is to make genetic tests whose implications are clearly understood available to the small number of people who would clearly benefit. One report found that only 15% of breast cancer patients who met specific NCCN testing guidelines for hereditary cancers underwent genetic testing. 2017 survey This study examined data from the National Household Health Survey from 2005 to 2015.

“I argue that we need to focus on people who are at high risk for breast cancer and have not yet been identified.” Dr. Tuya Palassociate director for cancer health disparities at Vanderbilt Ingram Cancer Center and vice chair of the NCCN Guidelines Committee on Genetic/Familial High Risk Assessment for Breast, Ovarian, and Pancreatic Cancer.

Patients can fail because no one tells them they should get tested. In one analysis, 56% of high-risk breast cancer patients who did not undergo genetic testing the doctor did not recommend it.

Even if a doctor recommends genetic testing, the doctor may lack the expertise to determine which tests a patient needs and how to interpret the results. That is the role of a genetic counselor, but the rank is stretched thin.

The consequences can be serious. in the study Of the 666 breast cancer patients who underwent genetic testing, half of those at average risk for hereditary cancer underwent double mastectomy based on the following test results:Variants of uncertain significance”, which is clinically impractical. About half of surgeons reported that they manage such patients in the same way as patients with cancer-causing mutations.

“The bulk of our research shows that there is still room for improvement in providing clinicians with the understanding they need.” AS Dr. Alison Kuriandirector of the Women's Clinical Cancer Genetics Program at Stanford University and co-author of the study.

This article is from KFF Health News.