In the IDENTIFY study, reported in The New England Journal of Medicine, Turriff et al found a high incidence of maternal occult cancer associated with unusual or nonreportable prenatal cell-free DNA (cfDNA) findings in fetal aneuploidy screening.
Study Details
In the ongoing study, performed at the National Institutes of Health, cancer screening was performed in pregnant or postpartum women who did not report signs or symptoms of cancer but who received unusual clinical cfDNA-sequencing results or results that were nonreportable (ie, fetal aneuploidy status could not be assessed) from 1 of 12 commercial laboratories in North America. A uniform cancer-screening protocol was used, including rapid whole-body MRI, laboratory tests, and standardized cfDNA sequencing for research purposes with a genome-wide platform.
Key Findings
Maternal cancer was identified in 52 of 107 participants (48.6%) in the initial cohort. Among the 52 participants with cancer, the most common types were lymphoma (59.6%), colorectal cancer (17.3%), and breast cancer (7.7%).
The sensitivity and specificity of whole-body MRI in detecting occult cancer were 98.0% and 88.5%. Physical examination and laboratory tests provided little information in identifying maternal cancer.
Research sequencing showed that 49 women had a combination of copy-number gains and losses across multiple (at least three) chromosomes; cancer was present in 47 (95.9%) of the women with this sequencing pattern. cfDNA sequencing patterns with only chromosomal gains (multiple trisomies) or only chromosomal losses (one or more monosomies) were found in women with nonmalignant conditions, including fibroids.
The investigators concluded: “In this study, 48.6% of participants who received unusual or nonreportable clinical cfDNA-sequencing results had an occult cancer. Further study of DNA-sequencing patterns that are suggestive of occult cancer during prenatal screening is warranted.”
Diana W. Bianchi, MD, of the National Institutes of Health, Bethesda, Maryland, is the corresponding author of The New England Journal of Medicine article.
Disclosure: The study was funded by the National Institutes of Health Intramural Research Programs. For full disclosures of the study authors, visit nejm.org.
