Prenatal Screening in the Detection of Maternal Cancer

Each year there are more than 3 million pregnancies in the United States alone.¹ These mothers-to-be will have the option to undergo various prenatal screening options primarily used to screen for chromosome abnormalities, such as Down syndrome.

One of these options, called non-invasive prenatal screening (NIPS), is a relatively new technology that analyzes fragments of placental DNA circulating in the mother’s bloodstream. It is a popular choice for many mothers, as it is now considered a superior screening test compared to other long-standing screening options and doesn’t carry the same risk to the fetus as invasive tests, such as chorionic villus sampling or amniocentesis.

Interestingly, this technology has also shown to be able to identify the presence of maternal malignancies. While the co-existence of cancer and pregnancy is quite rare (approximately 1 in 1000-2000 pregnancies), it is possible.² Just like a placenta shreds DNA into the mother’s bloodstream, so do tumors. This can lead to NIPS returning an abnormal result, but instead of the abnormality originating from the fetus, it has originated from a tumor.

Starting around 2014, screening with NIPS became more popular, and cases of women with abnormal NIPS due to the presence of cancer began to appear.

In 2015, an article was published in the MIT Technology Review recounting the experience of Erin Lindquist, a Biology Professor.³ At the time, Erin was 36 years old and pregnant with her second child. She elected to undergo NIPS screening, but when the results came back abnormal, showing an extra copy of chromosome 13 and a missing copy of chromosome 18, she was shocked. She decided to pursue additional testing through amniocentesis that showed that her child was perfectly healthy. However, soon after her son’s birth, she was diagnosed with a rare form of metastatic cervical cancer, revealing that the abnormal NIPS results were hers.

A recent study published in Chemical Chemistry evaluated the use of NIPS for cancer detection and treatment monitoring in both pregnant and non-pregnancy individuals.² The study showed a sensitivity of 26% for identifying cancer-specific chromosome copy-number alterations (CNAs) via NIPS.  Higher sensitivity levels were reported with more advanced cancers while other tumors had unreportable levels of CNAs. Lastly, they showed a drop in the NIPS levels in women undergoing treatment for cancer, showing the potential for NIPS to monitor treatment.

There is still a long way to go before NIPS would be routinely used as a cancer screening tool, but there is no doubt that accidental cancer detection is a possibility.

In the summer of 2020, the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) released a joint statement recommending that NIPS be offered to all pregnant women regardless of age or baseline risk.

This announcement will lead to more women undergoing NIPS and increases the possibility of incidental detection of maternal malignancies. Ordering physicians need to be aware of this possibility and inform their patients of potential findings.

If an abnormal NIPS result is returned, best practice is to refer the patient to a genetic specialist to review the results and the options moving forward.

References

1. Hamilton BE, Martin JA, Osterman MJK. Births: Provisional data for 2019. Vital Statistics Rapid Release; no 8. Hyattsville, MD: National Center for Health Statistics. May 2020. Available from: https://www.cdc.gov/nchs/data/ vsrr/vsrr-8-508.pdf.
2. Lenaerts L, Che H, Brison N, et al. Breast Cancer Detection and Treatment Monitoring Using a Noninvasive Prenatal Testing Platform: Utility in Pregnant and Nonpregnant Populations. Clin Chem. 2020;66(11):1414-1423. doi:10.1093/clinchem/hvaa196
3. Nowogrodzki, A. When A Fetus’s Test Finds a Mother’s Cancer. MIT Technology Review. July 13, 2015.