Clinically Silent Maternal Cancer Detectable By Prenatal Testing

Diana W. Bianchi, M.D. Executive Director, Mother Infant Research Institute Vice Chair for Research and Academic Affairs, Department of Pediatrics Tufts Medical Interview with:
Diana W. Bianchi, M.D.

Executive Director, Mother Infant Research Institute
Vice Chair for Research and Academic Affairs
Department of Pediatrics
Tufts Medical Center

Medical Research: What is the background for this study? What are the main findings?

Response: Noninvasive Prenatal Testing (NIPT) is the fastest growing genetic test. It has been available since late 2011. Over 2 million tests have been performed worldwide. Cancer in pregnancy is rare, and only occurs in 1 in 1,000 pregnant women. About 0.2 per cent of noninvasive prenatal tests that use sequencing of maternal plasma DNA have a so-called “false positive” result. In most cases this is not an error, but there is a biological explanation for the discrepancy between the abnormal noninvasive prenatal test result and a normal fetal chromosome result obtained from a diagnostic procedure, such as amniocentesis or chorionic villus sampling (CVS). We are very interested in the underlying biological explanations for the false positive cases, and it turns out that a clinically silent tumor in the mother is one of them. The mother’s tumor is shedding DNA into her blood that is detected by the prenatal test.

In a large clinical dataset of over 125,000 pregnant women who had a DNA sequencing screen for fetal chromosome abnormalities there were 10 women who were subsequently found to have cancer. We retrospectively analyzed the DNA sequencing results in 8 of these women and found that they had abnormalities in multiple areas of the genome, suggesting that it was DNA from the tumor that was shed into the maternal blood and being detected by the prenatal screen.

The noninvasive prenatal sequencing test result that was most suggestive of a cancer risk was the presence of more than one aneuploidy. This finding was present in 7 of the 10 women who had cancer.

In three of the eight women we studied it was the abnormal prenatal test result that triggered a subsequent work-up that led to the diagnosis of cancer.

Medical Research: What should clinicians and patients take away from your report?

Response: Make sure that the patient knows that the noninvasive prenatal test sequences both her own DNA and the DNA from the placenta, so an abnormal result does not necessarily mean that something is wrong with the baby. All abnormal noninvasive prenatal test (NIPT) results need to be confirmed with a fetal diagnostic karyotype.  The patient should not take irrevocable action until she has the results of the fetal karyotype. Cancer is only a possible explanation if there is a discrepancy between the Noninvasive Prenatal Testing result and a normal fetal karyotype (obtained by amniocentesis or CVS).

Medical Research: What recommendations do you have for future research as a result of this study?

Response: We need to do a prospective study to determine what is the pattern of genome imbalance that is most closely associated with a risk of cancer. Furthermore, we need to determine what is the appropriate subsequent medical work-up for pregnant women who have highly unusual noninvasive prenatal testing results, such as the detection of multiple aneuploidies.


Bianchi DW, Chudova D, Sehnert AJ, et al. Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies. JAMA. Published online July 13, 2015. doi:10.1001/jama.2015.7120.

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Diana W. Bianchi, M.D. (2015). Clinically Silent Maternal Cancer Detectable By Prenatal Testing