Recent findings from the National Institutes of Health (NIH) IDENTIFY study found undetected cancers in 48.6% of pregnant people who received abnormal or non-reportable non-invasive prenatal testing (NIPT) results for prenatal cell-free DNA (cfDNA) testing used to screen for chromosomal disorders in the fetus.
The results reported in the New England Journal of Medicine, showed that the cancers found included colorectal, breast, lung and pancreatic cancers, as well as lymphoma, cholangiocarcinoma, and renal carcinoma.
NIPT analyzes cfDNA released from the mothers blood and stems cells and were designed to identify the risk of the baby developing common genetic conditions such as Down syndrome, and Trisomies 13, 18, or 21. But a few years after these blood tests became widely available, reports of falsely abnormal NIPT began to appear, but follow up testing via either amniocentesis or chorionic villus sampling (CVS) of the baby was normal.
Diana Bianchi, MD, head of the prenatal genomics and therapy section at NIH, speaking in an informational video on the IDENTIFY study website said: “In some cancers, the tumor sheds DNA into the mother’s blood, and it is the genetic abnormalities from the tumor that are being detected by NIPT. Over 100 cases of maternal cancer detected by NIPT have now been documented, commonly in women who are feeling well and have no symptoms.”
The IDENTIFY study evaluated 107 participants with unusual or non-reportable NIPT results, employing whole-body magnetic resonance imaging (MRI), laboratory testing, and advanced cfDNA sequencing. A total of 52 participants were diagnosed with cancer, including breast, colorectal, and pancreatic cancers, as well as lymphoma and renal carcinoma. Whole-body MRI emerged as the most effective method for detecting these cancers, with a sensitivity of 98% and specificity of 88.5%.
According to Christina Annunziata, MD, PhD, senior vice president of the American Cancer Society, the detection rates for maternal cancer when multiple abnormalities appear on NIPT have varied across studies. “Some of the earlier studies estimated the risk of maternal cancer to be between 20% and 45% when multiple abnormalities are detected by NIPT. More recent studies have documented a higher rate of cancer detection, ranging from 70 to 86%,” she said in a video on the IDENTIFY study website.
The IDENTIFY study also aims to address gaps in understanding and response to abnormal NIPT results. “Currently, when these false positive or non-reportable results come up in prenatal clinics, there’s a lot of confusion,” Bianchi said. “Many OB-GYN or other healthcare providers have never seen these types of results before, and they may be unfamiliar with their significance for the mother’s health.”
The study uses a standardized protocol for cancer evaluation. Researchers found that cfDNA sequencing patterns could help distinguish between cancer and other conditions, such as fibroids or clonal hematopoiesis, a precancerous state. For instance, participants with sequencing patterns showing a mix of chromosomal gains and losses had a 95.9% likelihood of cancer, compared to other patterns more commonly associated with benign conditions.
The research indicates that women who receive abnormal or non-reportable NIPT results should seek additional testing.
“Pregnancy is not a reason to delay being evaluated. We encourage any person who receives a non-reportable or false positive NIPT result to pursue a timely and thorough evaluation, even if you feel well and don’t have any symptoms. Most cancers have a better chance of cure when diagnosed and treated at an early stage and many cancer treatments can be given safely during pregnancy,” Annunziata said.
