In a Dutch study reported in the Journal of Clinical Oncology, Heesterbeek et al found that results of noninvasive prenatal testing for fetal aneuploidy screening using cell-free DNA derived from maternal plasma raised suspicion of maternal malignancy in a very small proportion of pregnant women. According to their report, malignancies were present in a high proportion of patients with suspicious findings.
Study Details
The study involved analysis of noninvasive prenatal testing assays performed in 231,896 women between April 2017 and April 2020 as part of a Dutch nationwide noninvasive prenatal testing implementation study (TRIDENT-2).
In 63,444 assays (27.0%), aneuploidy analysis of chromosomes 13, 18, and 21 only was requested (targeted). In 168,452 assays (73.0%), analysis of all autosomes was requested (genome-wide).
In 231,896 pregnant women, a low percentage (0.02%) of noninvasive prenatal testing results were assessed as indicative of a maternal malignancy. However, when multiple chromosomal aberrations were found, the risk of a confirmed malignancy was considerably high.— Heesterbeek et al
Tweet this quote
Key Findings
Overall, a malignancy-suspicious noninvasive prenatal testing finding was reported in 53 cases (0.02%).
A malignancy-suspicious noninvasive prenatal testing result was found in 50 cases of genome-wide testing (0.03%). Of the 50 patients, 2 appeared to have prior diagnosis of a myeloproliferative neoplasm and were excluded from analysis. Among the remaining 48 cases, a malignancy was confirmed in 16 (33.3%). Among the 48 patients, 23 had two or more chromosomal aberrations; all 16 malignancies (69.6%) were found in these 23 patients.
A malignancy-suspicious noninvasive prenatal testing result was found in three cases of targeted testing (0.005%). Malignancy was confirmed in two (66.7%) of the three patients.
Among the 18 malignancies, 12 were of hematologic origin, including Hodgkin lymphomas in 7 (all classified as classic Hodgkin lymphoma) and non-Hodgkin lymphomas in 4 (all classified as primary mediastinal B-cell lymphoma). Breast cancer was found in four cases (triple-negative in two, estrogen receptor/progesterone receptor–positive/HER2-negative in one, and estrogen receptor/progesterone receptor–negative/HER2-positive in one). One patient each had acute myeloid leukemia, colorectal carcinoma, and carcinoma of unknown primary, respectively.
The median maternal age at noninvasive prenatal testing for the 18 patients with a confirmed malignancy was 35 years (range = 26–42 years).
The investigators concluded, “In 231,896 pregnant women, a low percentage (0.02%) of noninvasive prenatal testing results were assessed as indicative of a maternal malignancy. However, when multiple chromosomal aberrations were found, the risk of a confirmed malignancy was considerably high. Referral for extensive oncologic examination is recommended and may be guided by tumor-specific hallmarks in the noninvasive prenatal testing profile.”
Merryn V.E. Macville, PhD, of the Department of Clinical Genetics, Maastricht University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Netherlands Organization for Health Research and Development. For full disclosures of the study authors, visit ascopubs.org.
