Non-invasive prenatal testing (NIPT) for chromosomal foetal disorders is used increasingly to test for conditions such as Down's syndrome. NIPT examines DNA from the foetus in the mother's blood, and therefore does not carry the risk of miscarriage involved in invasive testing methods. Now, for the first time, researchers have found another advantage of NIPT; it can detect maternal cancers at an early stage, before symptoms appear. The study, to be presented to the annual conference of the European Society of Human Genetics today (Saturday), is published simultaneously in the journal JAMA Oncology.
Nathalie Brison, PhD, a senior scientist in the Clinical Cytogenetics laboratory at the Centre for Human Genetics, UZ Leuven, Leuven, Belgium, will tell the conference that the team had set out to increase the accuracy of the NIPT test in order to overcome some of the technical problems that can cause it to come up with false negative or false positive results when screening for chromosomal disorders in the foetus. Down's, or trisomy 21, is the most frequent chromosomal abnormality, and occurs in about one in 700 live-born babies. The risk of giving birth to a baby with Down's increases with the age of the mother, and rises sharply from the age of 36 years.
"We therefore felt it important that we improved the accuracy of the test," Dr Brison says. "Even though it is very reliable, we believed that we could make it even better, and in doing so we could also find other chromosomal abnormalities apart from the traditional trisomy syndromes - Down's, Edward's (trisomy 18), and Patau (trisomy 13). Using the new, adapted test in over 6000 pregnancies, and looking at other chromosomes, we identified three different genomic abnormalities in three women that could not be linked to either the maternal or foetal genomic profile. We realised that the abnormalities bore a resemblance to those found in cancer, and referred the women to the oncology unit."
Further examination, including whole body MRI scanning and pathological and genetic investigations, revealed the presence of three different early stage cancers in the women: an ovarian carcinoma, a follicular lymphoma, and Hodgkin's lymphoma. Although this incidence is within the range to be expected in the normal population (one per 1000-2000 person years in women aged 20 - 40), without NIPT these cancers would have been unlikely to have been detected until they became symptomatic, and therefore at a much later stage.
"Considering the bad prognosis of some cancers when detected later, and given that we know that it is both possible and safe to treat the disease during pregnancy, this is an important added advantage of NIPT," comments principal investigator Professor Joris Vermeesch, Head of the Laboratory for Cytogenetics and Genome Research at Leuven. "During pregnancy, cancer-related symptoms may well be masked; fatigue, nausea, abdominal pain, and vaginal blood loss are easily interpretable as a normal part of being pregnant. NIPT offers an opportunity for the accurate screening of high risk women for cancer, allowing us to overcome the challenge of early diagnosis in pregnant women."
Two out of the three diagnosed women were treated, one of them during her pregnancy. She subsequently gave birth to a healthy girl. The third had indolent disease that was not considered to be in need of treatment at that stage. Follow-up investigations in the treated women showed that NIPT had the additional advantage of allowing the effectiveness of treatment to be monitored, and the researchers were able to see that the chromosomal profiles became normal during and after chemotherapy.
Because the procedure involves looking at chromosomes other than 13, 18, and 21, women taking part were informed about the possibility of incidental findings. "However, our study feeds into the ethical debate about whether or not to report incidental findings to patients, and also has implications for the current political discussions concerning reimbursement and funding of NIPT by national health care systems," says Prof Vermeesch.
The results suggest that NIPT might enable the detection of pre-symptomatic cancers not just in pregnant women, but more widely. "We now know that it is possible to offer the accurate detection of chromosomally imbalanced cancers to the general population via minimally invasive screening methods," says Dr Brison. "The normalisation of the NIPT profile in these patients following treatment indicates that we can also measure response to treatment as early as after the first administration of chemotherapy. Of course, larger scale studies will be required to validate these results further, but we are confident that we have made an important step towards the possibility of wide-scale, effective, non-invasive cancer screening capable of detecting disease at an early stage."
European Society of Human Genetics