When Kathleen Aukstikalnis was expecting her first baby, she turned to a common prenatal test that a lot of her friends had gotten done during their pregnancies.
The simple blood test looks at DNA that's floating freely in a pregnant person's bloodstream. It searches for bits released by cells in the placenta, which should have the same genetic make-up as the fetus.
Over the last decade, this kind of genetic test has become the go-to method for screening pregnancies for chromosomal abnormalities like Down syndrome, and it's reduced the number of invasive amniocentesis procedures dramatically. Aukstikalnis hoped the test would provide peace of mind, and was also excited that the test would reveal her baby's sex.
"That's really all that I was expecting," she says. "I didn't know that you could find out something about yourself from it."
But she did find out something about herself. In fact, this test sent her on a medical odyssey, one that shows the promise – and challenges – of blood tests that can potentially zero in on DNA released by cancer cells.
A cancer moonshot
An expectant mother's bloodstream doesn't just contain bits of free-floating DNA associated with the fetus. It's also chock full of DNA released by her own cells. And if some of those cells are malignant, that can affect the test results – acting as a kind of unasked-for cancer screening.
A blood test that can screen for multiple cancers at once by looking at DNA has been something that researchers have been working towards for years. It's currently a major focus of President Biden's Cancer Moonshot research initiative.
"Imagine a simple blood test during an annual physical that could detect cancer early, when the chances of a cure are best," Biden said recently, adding that the National Cancer Institute is planning a large clinical trial to explore this approach.
One such cancer screening test is even commercially available – but no medical association recommends this kind of testing and no such tests have been approved by the Food and Drug Administration.
That's because although there's some data suggesting that certain blood tests that target free DNA might be very good at detecting cancer, there's no definitive studies showing that using them for screening will actually improve people's health outcomes, says Lori Minasian, deputy director for the division of cancer prevention at the National Cancer Institute.
"Do we really understand that in all of these different cancers at the earliest stages, they're releasing this DNA in a way that is reproducible, that we can measure and understand that it's early or late?" asks Minasian. "There's so much we don't know about this. We need to do the trials so we can get the information."
'I wasn't thinking about myself'
In the meantime, pregnant people like Aukstikalnis can be blindsided by information that they never expected as they seek out a test that they thought would just tell them something about the pregnancy.
After she'd gotten blood drawn and sent it off for testing of the free-floating DNA in her blood, a nurse called and said there'd been some kind of error and the test hadn't produced reportable results. So Aukstikalnis went in and had her blood drawn again.
"It ended up being the same kind of scenario," she says.
Her nurse-midwife said she'd never had a patient who got this kind of inconclusive result, and recommended a consultation with a genetic counselor to figure out what might be going on.
"I wasn't thinking anything about myself, really, at all," recalls Aukstikalnis. "I was more worried about the baby."
She and her husband, Andrew, talked with the counselor, who told her that the oddities seen in her blood sample were so rare, no one knew for sure what might be causing them. Physicians had observed, though, that pregnant people who got these kinds of test results sometimes later were diagnosed with benign or malignant tumors.
"So that was really difficult to wrap my head around," says Aukstikalnis.
A genetic needle in a DNA haystack
Doctors already have some experience with looking for the DNA of cancer cells in the blood, because they occasionally do so for patients who are known to have advanced cancer. In those cases, these tests help to make decisions about how to best treat these patients.
It isn't hard to detect malignant DNA in these patients, because their bodies usually have a lot of cancerous cells that are shedding DNA, explains Colin Pritchard, professor of laboratory medicine and pathology at the University of Washington.
But catching cancers early with a blood test? That's another story.
"Early detection is so much harder. It's really a beast," says Pritchard, adding that trying to spot DNA released into the blood by a small number of cancerous cells is a needle-in-the-haystack problem.
To him, it seemed like an unlikely way to screen for cancer. But recent technological advances have made him reconsider.
"I went from being a huge skeptic," says Pritchard, "to being like, 'Well, okay, this is a viable approach and this could work.'"
The trouble is, "we don't know who should be tested," he adds. "How old should you be? Should you only be tested if you have a family history of cancer?"
And if the screening test indicates the possible presence of a malignancy, what kind of follow-up testing needs to be done? Insurance companies may balk at paying for expensive tests to hunt for cancers that might not even exist, based on the results of a new-fangled screening strategy that hasn't been proven cost-effective.
All this uncertainty is what hit Aukstikalnis and her spouse when they spoke with the genetic counselor. The counselor suggested that they might consider enrolling in a clinical trial at the National Institutes of Health that was seeking people who had gotten these ambiguous test results when seeking information about their pregnancies.
The trial, called IDENTIFY, was designed to figure out the full range of what these results might mean, so that doctors in the future would have a better sense of what to tell their patients.
Each participant in the trial would get an all-expense-paid trip to the NIH's clinical center, the biggest research hospital in the world, for a wide array of diagnostic tests including a full-body MRI scan, which is safe to do during pregnancy.
"It was kind of like a no-brainer for me that we were going to go with NIH and see what they could find out about it," says Aukstikalnis, "and go from there."
What to do with these results
Not everyone facing that choice made that decision. After all, most of the people getting these inconclusive prenatal test results are young, apparently healthy, and pregnant, notes Amy Turriff, a genetic counselor at the NIH.
"I think to the average person, if you have cancer, you don't feel well, you have some lump, bump, some sort of scary symptom," says Turriff, "and that's just not the experience of the people being referred to us."
Some people have declined to participate in the study because they've gotten the idea from their doctor, or even a cancer specialist, that the test results most likely don't mean anything.
Diana Bianchi, director of the National Institute of Child Health and Human Development, says that she and her colleagues faced that kind of skepticism when they started the IDENTIFY study.
"Everyone thought we were a little bit crazy in the beginning," recalls Bianchi, who says the general attitude was that "there's no way these healthy women are going to have cancer."
But that's not what their trial's results suggest so far, says Bianchi, who hopes to publish interim findings from the study, which is still enrolling participants, in 2024.
"Of the ones who have been enrolled and have had the full workup, over half of them do have a tumor," says Bianchi. "So this is not a trivial finding. Our take home message is, this really needs to be taken seriously."
The researchers have found a variety of malignancies. "What we've found most commonly is lymphoma. But we found extremely rare cancers as well, like 1-in-a-million type of cancers," says Bianchi. One woman had a cancerous mass in her abdomen the size of a grapefruit.
These findings are similar to those of a new study out of the Netherlands, which followed up 48 pregnant women who had suspicious results from one of the cell-free DNA prenatal tests. Eighteen of the women turned out to have malignancies, most often lymphomas.
An overwhelming experience
When Aukstikalnis and her spouse went to the NIH clinical center in July of 2021, to get their slew of tests, they hadn't expected to hear the results right away. And she still didn't really think the tests would find that she was sick.
But at the end of the day, a team of doctors sat them down and said that it looked like she likely had lymphoma. The news came as a shock.
"Hearing that news that you have cancer, it's hard to describe. It's just such, like, an overwhelming experience," she says. "And then you're also pregnant at the same time. Your emotions are kind of all over the place. It was definitely really difficult."
The NIH team helped get her set up with caregivers in her home state, and a biopsy confirmed the diagnosis.
She started chemotherapy even before her baby was born--something that can be done completely safely--and got a lot of help from family and friends, plus online support communities for pregnant women with cancer such as Hope for Two.
In November of last year, her family welcomed a baby girl named McKenna.
"Everything went really smoothly with delivery and she was perfectly normal, she is perfectly healthy," says Aukstikalnis. "That was always something I was nervous about, was it the right decision to get treatment while I was pregnant, you know, could it still end up causing issues? And it didn't. She is doing really well."
Unfortunately, even though Aukstikalnis had what appeared to be a clear scan after the first-line treatment that often puts people in remission, a subsequent scan showed that the lymphoma had likely returned.
She ultimately underwent a stem cell transplant this autumn that required a 26-day hospital stay, during which she wasn't able to see her husband or daughter except over twice-daily video chats.
Now that she's finally home with her family, she's trying to take it easy while her immune system slowly recovers.
"It's like being a newborn baby, all over again," she says. "It's going to take a long time, but I've made it this far, so I know that we can get there."
She hopes that her participation in the IDENTIFY study will help other women who face uncertain test results that might mean cancer.
"I'm incredibly grateful that I found out when I did and then found out I could get treatment at an early stage," she says. "Even though things have been really difficult, I would also say there have been a lot of positive experiences. It really shifted my focus to the things that matter most."
Copyright 2023 NPR. To see more, visit https://www.npr.org.
