The New England Journal of MedicinePrenatal cfDNA Sequencing and Incidental Detection of Maternal Cancer

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A new study examining unusual or nonreportable cell-free DNA (cfDNA) sequencing results during prenatal screening reveals significant implications for maternal cancer detection. This research provides critical data on the relationship between specific DNA sequencing patterns and occult cancer presence, offering potential guidance for clinical follow-up protocols.

Study Design:

• Ongoing study involving pregnant or postpartum individuals without perceived cancer symptoms who received unusual or nonreportable cfDNA results
• Participants (n=107) were identified through 12 commercial laboratories in North America
• Uniform cancer screening protocol implemented, including:
  • Whole-body MRI
  • Laboratory tests
  • Standardized cfDNA sequencing using genomewide platform
• Primary outcome measured: presence of cancer after initial screening
• Secondary analyses focused on test performance metrics

Key Findings:

• 48.6% (52/107) of participants were diagnosed with cancer
• Whole-body MRI demonstrated:
  • 98.0% sensitivity
  • 88.5% specificity
• Research sequencing identified:
  • 49 participants with combined copy-number gains/losses across ≥3 chromosomes
  • 95.9% (47/49) of these participants had cancer
• Chromosomal pattern distinctions:
  • Multiple trisomies or isolated monosomies were associated with nonmalignant conditions
• Physical examination and standard laboratory tests showed limited utility in cancer identification

HCN Medical Memo
This study highlights the need for standardized follow-up protocols when unusual cfDNA results are encountered during prenatal screening. The high correlation between specific genomic patterns and cancer presence suggests that careful attention to cfDNA sequencing patterns could help identify high-risk cases requiring immediate oncologic evaluation.

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