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Cancer and NIPT: The good and the bad.
A message from the editor: Prof. Joris Vermeesch, Ph.D.
For some time, our laboratory reports abnormalities in the NIP test beyond just fetal trisomy 21, 18 and 13 or other fetal chromosomal anomalies. Because the fraction of fetal cfDNA exists against a high background of maternal plasma cfDNA, NIPT profiling can detect maternal chromosomal abnormalities, such as maternal mosaicisms or malignancies, as well. We have been reporting the presence of maternal cancers. Amongst about 90000 NIPTs, 15 women were informed to potentially have a cancer. Those women are first counseled by a clinical geneticist and subsequently referred to the oncology unit of the hospital. Since the NIPT cannot identify the origin of the cancer, the women undergo a whole body MRI. Upon further clinical examination, 12 cancers and 2 premalignant conditions were identified, of which one was found to be a prelude to a hematological malignancy more than 3 years after NIPT testing. Hence, when carefully implemented, the accuracy of cancer detection during pregnancy is quite high.
The co-existence of cancer and pregnancy is a rare phenomenon with an estimated incidence rate of 1 in 1000 to 2000 pregnancies. However, as women in developed countries tend to delay childbearing, incidence numbers are increasing. Pregnant women are at high-risk of not being diagnosed at early cancer stages because cancer symptoms (such as fatigue, nausea, or abdominal discomfort) can be misinterpreted as physiologic gestational symptoms. In particular for breast cancer, normal physiological changes in the breast during gestation increase the challenges in rendering a correct pathological evaluation, which may lead to a delayed cancer diagnosis and a negative impact on clinical outcome. On the other hand, accumulating evidence indicates that initiating cancer treatment during pregnancy has no adverse effect on pediatric outcome. Instead, an early start of chemotherapy may improve the prognosis of the mother similar to that of non-pregnant women. These findings underscore the value of reporting cancers if, fortuitously detected during NIPT.
From our practice, we notice a lack of awareness of the potential aetiologies of aberrant NIPT results. The presence of a maternal malignancy can result in an unsuccessful NIPT. This is because the majority of cancers, leukemias or lymphomas are characterized by chromosomal anomalies. Those malignancies, like the placenta, shed their DNA in the maternal blood. When performing NIPT, the fetal and malignant DNA are both analysed together and it cannot be distinguished which DNA is tumoral and which is fetal. Hence, the tumor DNA confounds the NIPT. As a consequence, pregnant women with a confirmed neoplastic disease should not have NIPT testing for fetal aneuploidy screening since NIPT results cannot accurately be applied to assess the fetal chromosomal constitution nor sex in this condition. A tumor may not only result in a bad test, it could also result in a false negative or positive test result. By now, a number of retrospective and prospective reports have shown that NIPT detection of tumor-derived cfDNA (ctDNA) in the bloodstream of pregnant women with an occult malignancy, was causative for the deviating NIPT result.