Non-invasive prenatal testing for cancer detection and treatment monitoring in pregnant women

Objectives. We developed and implemented a genomewide cell-free DNA (cfDNA) analysis pipeline, coined GIPSeq (Genomic Imbalance Profiling from cfDNA SEQuencing) for non-invasive prenatal testing (NIPT), allowing genomewide detection of foetal and maternal (sub)chromosomal imbalances. Using this pipeline in about 75.000 asymptomatic pregnant women we incidentally identified 8 maternal malignancies following the detection of cancer-specific copy number alterations (CNAs) in cfDNA. Based on these incidental findings, we set out to explore the sensitivity of GIPSeq for cancer detection and treatment monitoring in pregnant women. Methods. Pregnant women (n=24) diagnosed with invasive breast cancer (i.e. the most prevalent solid cancer type encountered during pregnancy) were recruited in University Hospitals Leuven. To investigate whether pregnancy-associated changes and/or the presence of fetal cfDNA in the maternal blood stream may impact the detection of circulating tumor cfDNA, we also included non-pregnant premenopausal breast cancer patients (n=28). A pre-treatment plasma sample was taken for GIPSeq analysis. In case of an aberrant GIPSeq profile, consecutive plasma samples were taken to assess treatment response. Tumour biopsy specimens were subjected to shallow sequencing to investigate the specificity of CNAs detected in cfDNA. Results. Genomewide CNA analysis of matched cfDNA and tumor DNA of all breast cancer cases has been performed. Statistical and bio-informatics analyses are currently ongoing and final results are expected to be ready by the end of summer for presentation at the CNAPS symposium. Conclusions. Enabling timely and proper identification of a malignancy and sensitive treatment monitoring through routine NIPT screening would have a major impact on the management of pregnant cancer patients, ultimately leading to an improved prognosis.