When Lisa DeAngelico found out she had Stage 4 breast cancer two years ago at age 47, she says one of the hardest parts about her diagnosis was telling her mother. That’s because her mother had already lost her sister and niece to the disease. They had hoped DeAngelico would be spared from the family curse.

So when DeAngelico’s doctor asked her whether she wanted to undergo DNA testing to better understand her family genetics, she agreed to offer a blood sample and meet with a genetic counselor.

“I hoped that if it did tell me I had a gene, I could tell others in my family that they should get tested early,” says DeAngelico, a hospital administrative coordinator in East Boston.

Yet the results revealed more than a family connection. When her doctor learned that DeAngelico had a mutation in the BRCA2 gene, he explained she also had a risk of ovarian cancer and advised her to have her ovaries and fallopian tubes removed to prevent the cancer from developing. He also put her on an oral drug called Lynparza that had been approved in January 2018 for breast cancer patients with her exact inherited mutation.

In a new era of precision medicine, the role of genetics is becoming increasingly critical to determine who might benefit from such therapies that go after specific cancer-causing genetic mutations. A growing number of oncologists now order a DNA analysis of patients’ cancerous tumor tissue obtained through a biopsy to better understand how patients’ unique biology might drive their treatment.

More doctors also are encouraging breast cancer patients to have their DNA sequenced through a simple blood test to reveal mutations that can be passed down from parent to child. These inherited mutations account for 10 percent of the nearly 270,000 estimated cases of breast cancer in 2019 in U.S. women and nearly 42,000 deaths, according to the National Cancer Institute. (And about 2,670 cases and 500 deaths in U.S. men.)

“There are new drugs for people with these inherited mutations that could help them control their cancer,” says Allison Kurian, an oncologist at Stanford Cancer Center, referring to the recent approval of two targeted therapies known as PARP inhibitors for patients with metastatic breast cancer who have a mutation in the BRCA1 or BRCA2 genes.

It’s not yet clear how long these drugs can keep patients’ cancer at bay — while some patients only lived several months longer, others are still responding successfully to them years later, she says. “But if we don’t test them, we won’t find out if they could benefit,” Kurian says.

Last year, the American Society of Breast Surgeons recommended that all breast cancer patients should have access to genetic testing to determine their lifetime hereditary risk — concluding that a “significant number” of cancer-causing mutations go undetected. Current guidelines by the National Comprehensive Cancer Network focus on high-risk patients, including those with a known family history or with advanced disease, yet fewer than 20 percent of these patients actually undergo testing, and the rate is even worse among minorities.

“The bottom line is that we shouldn’t be thinking about genetic testing any differently than a mammogram. It helps more women survive and not have to go through toxic chemotherapy,” says Kevin Hughes, surgical director of breast screening at Massachusetts General Hospital and professor of surgery at Harvard Medical School in Boston. He was part of the breast surgeons advisory committee that called for universal testing.

“It shows if she’s at risk for other cancers. Also you might be able to test her family and help them, too” he says.

Amid the enthusiasm for widespread testing for breast cancer patients, however, some doctors and genetic counselors are worried about how to handle the windfall of genetic information these new tests provide. When DNA sequencing for breast cancer genes became available in the mid-1990s, it tested only the BRCA1 and BRCA2 mutations and cost about $4,000. Now labs can look at 30 to 80 cancer genes at a time for as low as $250.

Yet identifying more mutations might not be helpful to doctors or patients. In what has become a common theme in genetics research, scientists are discovering genes faster than they can interpret them.

For example, one recent Johns Hopkins University School of Medicine and Vanderbilt University Medical Center study of genetic testing results of 100 metastatic breast cancer patients that was published last year in JAMA Oncology found that 14 patients had variants believed to cause cancer, yet in half those cases it was unclear how strong the link was. Even more confusing: 21 of the patients had what are known in genetics lingo as “variants of unknown significance” — meaning having no known impact on one’s health.

In other words, patients might receive reports with a lot of potentially worrisome information that doctors don’t know how to use — much less turn into meaningful treatment recommendations.

“We don’t know their cancer risk, and we have no treatments for them,” says Banu Arun, a medical oncologist at MD Anderson Cancer Center in Houston. “The harm is extra stress. Patients do the test, and then you have to tell them, ‘I don’t know what the results mean for you and for your family.’ ”

That disconnect prompted the American College for Medical Genetics and Genomics in December to issue a statement warning against universal testing, saying that guidelines should change when more data and treatment options become available.

Yet oncologist Ben Ho Park, co-author of the JAMA Oncology study, says the research identified two patients with BRCA mutations who fell though the cracks in the health-care system because they should have been tested under current guidelines but weren’t.

“There were a handful of patients we found who might respond to PARP inhibitors,” says Park, director of precision oncology at Vanderbilt-Ingram Cancer Center in Nashville, referring to the newly approved drugs that target particular DNA mutations. “That tells me we’re not even testing the people who should be tested. We need to be talking about this with our patients more often.”

As doctors hammer out the details of who should be tested and when, genetic counselors are often left with the job of trying to help patients cope with the emotional fallout: How should you react knowing you have something lurking in your DNA that might make you sick later?

In some cases, women have undergone potentially unnecessary surgeries to remove their breasts in response to a murky threat. An alarming 2017 study of 666 breast cancer patients who underwent genetic testing found that half of those with early stage disease who had “variants of unknown significance” had a double mastectomy.

“The patient is left with the idea that they’re at increased risk of cancer, but we don’t have any data. The findings might be important, but they might not mean anything, since most variants of unknown significance turn out to be benign,” says Lisa Madlensky, director of the family cancer genetics program at University of California at San Diego. “Still, for patients, it’s hard to ‘unsee’ something.”

After Kristel Baffa was diagnosed with Stage 3 breast cancer in May, a friend who works at Force, a nonprofit organization devoted to hereditary breast and ovarian cancer, suggested Baffa get genetic testing. Two of her aunts were breast cancer survivors, and a grandmother had died of the disease.

“My doctor said it would be a good idea, and I was in panic mode,” says Baffa, 44, a financial recruiter from O’Fallon, Ill. “I wanted to know if I had passed on something to my kids or if I’d have to get my ovaries removed.”

Yet the relief she felt after learning she didn’t have a BRCA mutation — which is linked to an elevated risk of breast and ovarian cancers — was overshadowed by the presence of another genetic variant of unknown significance.

“I didn’t even know that was an option,” she says of the vague result. “I thought the results would be black and white. It makes me anxious because they could find out later that it’s linked to another kind of cancer like ovarian cancer. Now I feel in limbo. With this kind of variant, there’s no action to take. You just wait around for science to tell us more.”

Although it probably will take years for researchers to better understand the roles of all aspects of our genetic code in creating disease, counselors agree there is one clear reason to embrace genetic testing: A chance to warn family members they also may be at risk. Children have a 50 percent of inheriting a genetic mutation from a parent.

And that poses its own complications. For some cancer patients reeling from a recent diagnosis, having difficult conversations with their family members can feel like too much to take on.

“Some patients say, ‘I can’t go there right now. I can’t think about my kids and their risk,’ ” says Gillian Hooker, president of the National Society of Genetic Counselors. “There’s a perception of guilt. You don’t get to decide what genes you pass on, but it’s still an emotion that comes up.”

Then there is the possibility that family members might not want to know too much.

According to an MD Anderson study that was published in December in the journal Genetics in Medicine, 150 patients who learned they had a hereditary disposition to cancer had told about 70 percent of their 825 first-degree relatives (parents, children or siblings). Yet only 30 percent of those relatives followed up with testing.

For Lisa DeAngelico, her mother and brother learned they also have the BRCA2 mutation that made her sick. Her mother opted to have her ovaries and fallopian tubes removed and now gets more frequent mammograms. Her brother is more vigilant about screening for prostate cancer, which is a risk for men with the mutation. DeAngelico says she is still hoping another brother, along with two male cousins and great aunt, will decide to get tested.

“Some people just don’t want to know,” she says. “Me, I like to know everything.”

That includes the news last spring that the new PARP inhibitor prescribed as a result of her DNA test had shrunk her tumor.