Prenatal Testing Identifies Occult Maternal Tumors

Occult maternal malignancies can be detected through noninvasive prenatal testing (NIPT), according to the results of a small preliminary study published in JAMA. Tumor detection was incidental, identified after the direct fetal karyotype was characterized as normal despite detection of aneuploidy.

Detection of these tumors could at least partly explain conflicting NIPT results, said the study authors led by Diana W. Bianchi, MD, of Tufts Medical Center in Boston.

Out of 125,426 NIPT samples, 3% (3,757) had one or more detectable aneuploidies involving 5 chromosomes (chromosomes 13, 18, 21, X, and Y), and 10 cases of cancer were identified upon further testing.

NIPT is a screening test to detect chromosomal abnormalities in a developing fetus using a simple blood draw from the mother. Cell-free DNA from maternal plasma is sequenced to identify the 3% to 15% of fetal DNA present in the pool of cell-free maternal DNA. Because this technique is not a direct fetal karyotype, there can be discrepancies between NIPT results and the actual fetal karyotype for reasons including maternal chromosome mosaicism or placental mosaicism.

Cell-free DNA from a tumor can also likely become part of the maternal circulation when dead or dying tumor cells are shed into the bloodstream. This can also be captured in the plasma sample analysis.

To understand the frequency at which maternal cancer can explain discrepancies in NIPT results, Bianchi and colleagues retrospectively analyzed DNA sequencing data from patients with aneuploidies detected by NIPT between 2012 and 2014.

Of the 10 cancers identified, eight were analyzed in detail. These cases had extensive copy-number changes involving amplifications and deletions of multiple chromosomes. Maternal cancers were most likely to occur when more than one aneuploidy was detected via NIPT, according to the study. Of 39 cases of multiple aneuploidies detected, seven were cancers (18%).

Based on the analysis, the authors estimated a 20% to 44% risk of maternal cancer when multiple aneuploidies are detected during NIPT.

The 10 cancers identified ranged from early-stage to metastatic disease. Three patients had B-cell lymphoma. There was also one case each of anal, neuroendocrine, and colorectal carcinomas, Hodgkin lymphoma, T-cell leukemia, leiomyosarcoma, and unspecified adenocarcinoma. The women in the study were between the ages of 23 and 39 at the time of diagnosis.

The rate of cancers in pregnant women reported in this study was 0.008%-tenfold lower than the 0.1% expected rate, according to the authors.

In an accompanying editorial, Roberto Romero, MD, DMedSci, of the National Institutes of Health, and Maurice J. Mahoney, MD, JD, of Yale University School of Medicine, noted that this is the first large-scale study that bolsters the theory that a false-positive NIPT result could be due to a maternal cancer.

“Given that it is likely that NIPT will increase in the coming years, an active dialogue among stakeholders (obstetricians, patients, laboratories, ethicists, policy makers, etc.) needs to take place to provide informed advice to potentially affected pregnant women and to guide the care of such patients,” they wrote.