My Confusing, Uncertain Journey After Genetic Testing

(Editor's note: Mary-Claire Piccart uses a pseudonym to protect the privacy of her health information.)

The oversized, boldfaced type and accompanying bar graph, in that shade of pink we associate with breast cancer awareness, blared from the page — but it was the percentage that stood out: 39.2.

The six-page clinical report included nearly impossible-to-understand medical jargon and acronyms, figures and disclaimers. But I just saw “39.2%” — my lifetime chance of developing breast cancer, according to the results of the genetic test my doctor recommended I have.

This figure is more than three times average rate (12.6%) for women of my age and ethnicity, according to the report.

At nearly 57, I had logged seven normal mammograms, but the recommendation to have genetic testing shouldn’t have come as a surprise. Breast cancer had killed my maternal aunt at 60, struck a sister at 50 and afflicted my deceased paternal grandmother and great-grandmother late in their long lives. My mother, who is in her early 80s, was diagnosed with breast cancer a few months after I took my genetic test.

Nonetheless, I was deeply unsettled by the alarming percentage that came back a few weeks after I supplied a sample of my DNA by spitting into a plastic tube.

As recently as 20 years ago, genetic tests cost thousands of dollars, which insurance rarely covered. Because of advances in technology, genetic testing’s predictive value has increased dramatically, while prices have simultaneously plummeted, prompting more insurance companies to cover it.

If my insurance hadn’t paid for my test, performed at a major research university near my home and supported by a board-certified genetic counselor, it would have cost about $250 out of pocket.

Lower costs and more discerning results have driven the popularity of genetic testing, making it big business: a $13 billion market in 2019, which is expected to more than double, to $28.5 billion, by 2026. That growth has been driven, in part, by the discovery 30 years ago of the hereditary breast cancer-causing gene mutations BRCA1 and BRCA2.

While breast cancer will strike one in eight U.S. women in their lifetimes, 45% to 65% of women with a BRCA mutation will develop breast cancer before 70, according to the National Breast Cancer Foundation. As those alarming odds emerged, clinicians urged patients with a family history of breast cancer to get genetic testing.

And earlier detection and treatment breakthroughs have made a dramatic difference. Breast cancer mortality rates plunged 40% from 1989 to 2017, resulting in nearly 376,000 fewer deaths, according to the American Cancer Society.

Female boomers and Gen Xers concerned about breast cancer are at the forefront of the genetic screening boom: 94% of 165,000 patients who underwent genetic testing from 2012 to 2016 with leading company Ambry Genetics were women, at a median age of 52, according to a 2019 clinical study. Of that number, nearly 84% pursued testing because of breast cancer in their families.

Under the Affordable Care Act, insurance companies must pay for BRCA mutation testing and genetic counseling for women meeting certain criteria. And in 2018, Medicare began covering the cost of cancer gene tests approved by the Food and Drug Administration. This has prompted more private insurance companies to also cover it.

To arrive at specific cancer risk percentages like the one I received, genetic testing companies can combine data from various clinical tools. In my case, there were two: the Tyrer-Cuzick Model and the polygenic risk score.

The older and more clinically accepted Tyrer-Cuzick Model assesses breast cancer risk based on personal data and family history provided by the patient. The newer polygenic risk score (PRS) relies on the genetic test and takes into account tiny mutations in thousands of genes that individually may have no, or a miniscule, effect.

But when geneticists use sophisticated algorithms to “combine a lot of these small variances, you can potentially have a big impact in predicting the risk” of developing a disease, says Holly DeLuca, senior manager of clinical affairs research at Ambry Genetics, which performed my test. Genetic companies then can combine those two figures to arrive at an estimated lifetime risk.

Although my genetic test showed that I don’t have a BRCA gene mutation, my family history combined with other individual gene mutations translated into my significantly elevated risk of developing the disease. Any risk above 20% means most insurance companies will cover extra screenings and medication. The goal is to treat breast cancer before symptoms develop or the disease progresses and makes treatment more invasive and expensive, or to even prevent it altogether.

Because of the high likelihood that they will develop breast cancer, some women who have BRCA gene mutations opt for preventive double mastectomies. Probably the most famous woman to publicly acknowledge taking this route was actress Angelina Jolie.

However, medical professionals haven’t agreed on standard guidelines regarding more invasive treatment, such as preventive surgery, for mutations other than of BRCA genes.

“It’s muddy for everybody,” says Joy Larsen Haidle, cancer expert for the National Society of Genetic Counselors and past president of the organization. “It’s important for patients and their providers to have a thoughtful conversation about what we do know and what don’t we know.”

Although my combined score was very prominently featured in my genetic testing report, I learned in a follow-up conversation with my genetic counselor that because PRS scores are so new and don’t have the rigorous scientific data backing them up that some other prediction models do, they aren’t considered when deciding on aggressive treatment options, unless a BRCA gene mutation is detected.

My PRS was calculated solely to confirm the Tyrer-Cuzick-based recommendation that I receive enhanced screenings. So, I now alternate mammograms and MRIs every six months, with the addition of ultrasounds if clinicians spot anything questionable in the first two tests. I’ll also soon begin taking raloxifene, a medication found to reduce the risk of breast cancer in patients at elevated risk of developing it.

As if this wasn’t enough, my genetic report revealed an unexpected, and an even vaguer potential risk. I also have what is known as a Spink1 gene mutation, a variation associated with an increased risk of pancreatic cancer in patients with a history of pancreatitis.

My great-aunt died of pancreatic cancer many years ago, in her 70s, but I’ve never had pancreatitis, nor has anyone in my immediate family. Under an ominous, boldfaced headline, “POSITIVE: Pathogenic Mutation Detected,” all my genetic testing report said about the mutation’s threat to me was, “cancer risks have not been well defined for this gene” and “the expression and severity of disease for this individual cannot be predicted.”

Given the exceptionally deadly nature of pancreatic cancer, this finding alarmed me more than the breast cancer risk. But up to 2.5% of the Caucasian population has the Spink1 mutation, Larsen Haidle says.

“A mutation of that gene is not uncommon,” she adds. “I feel your frustration. It’s a limitation of what we understand. It’s just not well known yet.”

Because screening guidelines for pancreatic cancer don’t exist, for now, my gastroenterologist recommends more frequent colonoscopies and added an endoscopy to my upcoming exam.

“In the ideal world, we’d find a genetic variant, and we’d be able to search records of people who’ve had that variant, and that would tell us which things are a risk, and which aren’t,” says Dr. J. Leonard Lichtenfeld, a board-certified oncologist and deputy chief medical officer of the American Cancer Society. “But we don’t have an ideal world.”

Federal law prevents medical insurers from raising policyholders’ rates or dropping coverage based on genetic test results. It also prohibits employment discrimination based on the findings. But while some states address it, federal law doesn’t prohibit discrimination related to life insurance, long-term care insurance or disability insurance coverage.

Despite genetic-testing companies’ reassurances, experts are pessimistic about how protected genetic test results actually are, and will be in the future. “Data is data — once it’s out there, it’s very hard to control,” said biomedical researcher James Hazel in a Feb. 16, 2019, Business Insider article. Hazel works at the Center for Genetic Privacy and Identity in Community Settings at the Vanderbilt University Medical Center in Nashville.

While I chose to have insurance pay for my genetic testing largely to facilitate coverage of additional screening and preventive care if I needed it, I agreed to write this article only if I could do so under a pseudonym because of broader privacy and discrimination fears.

Given these concerns, and the uncertain but potentially alarming nature of my genetic test results, I’ve wondered whether going through with it was the right decision.

Because of the sometimes-hereditary nature of cancer risks, my genetic counselor and doctors urged me to share my results with relatives,and to suggest that they also have genetic testing. My breast cancer-survivor sister, now 56, says she will probably get the test done, but our 50-year-old sister is unsure if she wants to know whether she’s “a cancer bomb.”

Aside from additional screening and lifestyle changes, such as reducing or eliminating alcohol and tobacco use, exercising and avoiding foods that could elevate disease risks, some experts agree there’s not much patients and their health care providers can do with the genetic test information.

“I can tell you your risk for lung cancer based on the top twenty studies in the world, but even knowing your PRS for lung cancer would mean that the best advice I can give to you is not to smoke, or maybe get a low-dose CT (computed tomography) scan once or twice every few years,” said Bertalan Meskó, a geneticist and director of The Medical Futurist Institute, in a June 24, 2019, Next Avenue article. “That is the absolute best advice I can provide, with or without me sequencing your DNA. And for most medical conditions, that is the case.”

One way to minimize anxiety and learn about the latest treatment options is to have genetic testing in consultation with a trained genetic counselor. (The National Society of Genetic Counselors offers a free directory of 3,300 professionals in the U.S. and Canada at FindAGeneticCounselor.com.)

“Genetic counselors are amazing health care practitioners and serve a vital role in the interpretation, translation and support of understanding genetic information,” says Jacqueline Savard, a bioethicist and lecturer at the Deakin University School of Medicine in Australia, who has studied patients’ perceptions and expectations about genetic testing.

I took the genetic testing path almost a year ago, and in the words of my primary care physician, I now have little choice but to plough ahead. I believe it was still the best option for me, but it’s been far more stressful and confusing than I expected.

My hope is that the additional screening I now undergo will detect any health problems early enough to minimize difficult or debilitating treatments, and that genetic research evolves so it can answer the sometimes-difficult questions it now forces us to ask.