Cancer Discovered From Prenatal Blood Test Can Save Lives

Veronica Hackethal, MD

June 11, 2015

The fact that noninvasive prenatal testing (NIPT) can identify presymptomatic cancer in pregnant women is illustrated in a review of three case reports published online June 5 in JAMA Oncology.

NIPT interrogates DNA present in maternal plasma. In pregnant women, the plasma contains fetal DNA, but in women who also have cancer, that plasma also contains cancer DNA, explained lead author Joris Robert Vermeesch, PhD, of the Center for Human Genetics, in Leuven, Belgium

"Women should be made aware that besides fetal anomalies, maternal conditions can be detected," Dr Vermeesch told Medscape Medical News.

"We demonstrate that in pregnant women with cancer, NIPT can identify tumors presymptomatically," he said.

The findings could potentially change clinical practice, he suggested.

The researchers sequenced maternal cell-free DNA from 4000 pregnant women. Three women had abnormal genome profiles that did not appear to belong to the mother or fetus, raising suspicion for maternal cancer. The women underwent whole-body scanning with MRI, which revealed cancer in all three. Pathologic and genetic tests confirmed the diagnoses. Genetic analyses of the tumor biopsy specimens confirmed that they matched the genome results found in the NIPT plasma.

The first patient had high-grade serous cancer in both ovaries with diffuse peritoneal spread, multiple metastases, and lymph node involvement. She underwent successful treatment after delivery. The second patient had follicular lymphoma and did not undergo treatment because of the slow-growing nature of this cancer. The third patient had Hodgkin lymphoma. She received treatment during pregnancy and gave birth to a healthy girl.

Although the results may be encouraging, more research is needed, according to Dr Vermeesch.

"We need to determine the specificity of the test to predict the presence of a cancer," Dr Vermeesch pointed out. "Larger cohorts need to be evaluated, [and] we need to determine which cancers can be detected."

Rapidly Growing Use

NIPT testing first became available in fall 2011. Since then, it has become the most rapidly growing molecular test in the history of medicine, says Diana W. Bianchi, MD, executive director of the Mother Infant Research Institute at Tufts Medical Center. Worldwide, about 1 million NIPT tests have been done, she said in a recent interview with Medscape Medical News.

NIPT can be carried out from around the tenth week of pregnancy and uses cell-free DNA to analyze parts of maternal and placental DNA from the mother's blood. After sequencing, these DNA snippets are compared to a reference genome, which in some cases comes from the mother's white blood cells.

NIPT focuses primarily on the viable trisomies 13, 18, and 21. It has been shown to detect Down syndrome at a rate of 99.2% and is "by far the best screen available," according to Dr Bianchi.

The test has low false positive rates and has contributed to a 50% to 70% worldwide reduction in invasive procedures such as amniocentesis. False positives can result, however, from a twin that died in the womb, abnormal or mosaic cells from the placenta, or a health condition in the mother, such as cancer. This is because both placental and tumor DNA can be found in maternal plasma, she explained.

Although NIPT represents a breakthrough in prenatal testing, the advanced technology is raising ethical considerations.

In an article published June 4 in Nature, Dr Bianchi emphasized that "consent is crucial" when mothers undergo NIPT, because it can reveal unexpected incidental findings.

Consent forms currently in use rarely mention that the test's findings could reveal information about the mother's health, she mentioned. Not all consent forms require the mother's signature, and they may not even mention incidental findings. Moreover, providers have "little guidance" about what to do about abnormal findings, and they need better education about the various prenatal blood tests available.

"Test providers need to rethink their consent forms to prevent unwarranted confusion and anxiety — not least, women deciding to terminate their pregnancies on the basis of wrong interpretations of test results," Dr Bianchi urged. About 6% of women who undergo prenatal DNA blood testing terminate their pregnancies without having chorionic villus sampling or amniocentesis, according to Dr Bianchi.

Professional societies, such as the American College of Medical Genetics and Genomics, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine, need to lead the way in providing education and clinical guidance, urged Dr Bianchi.

"Handled properly, the incidental findings emerging from prenatal tests could accelerate treatments and save lives — rather than just increase the anxiety of thousands of pregnant women," Dr Bianchi concluded.

Case Report Where Test Saved Lives

The lifesaving potential of test findings is illustrated by the case of Eunice Lee, MD, an anesthesiologist who spoke at the Future of Genomic Medicine Conference VIII, in La Jolla, California, in May 2015, as featured on Medscape Medical News.

While pregnant with her second child, Dr Lee received NIPT with MaterniT21 testing in her tenth week. When the test results came back as nonreportable, Dr Lee's obstetrician did not know how to interpret those results. On the advice of the head of the laboratory (Sequenom) that processed the test, Dr Lee underwent a workup for cancer with an MRI at 15 weeks' pregnancy. The MRI revealed a 7-cm mass in her sigmoid colon. She underwent surgery as soon as possible for removal of the mass, which placed her at risk for perforation. At 7 months' pregnancy, Dr Lee repeated the NIPT, the results of which were normal. She went on to give birth to a healthy boy.

"Taking this test at 10 weeks of pregnancy could very likely have saved my life and the life of my unborn child. If I had not had the test, the symptoms that I was feeling — the nausea, the constipation, the daily fatigue — might have been written off as first-trimester pregnancy symptoms," Dr Lee said.

"To any women who take this test and receive a nonreportable result, don't sit on it," Dr Lee said. "To the obstetricians who are practicing, I would say that if you have patients who have a result that is either nonreportable or different in any way, don't ignore it. You need to find out why the test came back as nonreportable, because in my case, there was definitely something that was causing the test to come back as abnormal."

"My baby, and the test, saved my life. I probably wouldn't be sitting here today if I hadn't taken the test," Dr Lee emphasized.

Dr Vermeesch is the founder of and a stockholder in Cartagenia, from which Dr Vermeesch's laboratory receives license fees. Dr Bianchi has received research funding and hornoraria from Illumina, Inc, and is a member of the Reproductive and Genetic Health Advisory Group.

JAMA Oncol. Published online June 5, 2015. Full text

Nature. Published online June 3, 2015. Full text

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