cfDNA integrity a potential biomarker for NACT response in breast cancer
medwireNews: Measuring plasma cell-free (cf)DNA integrity could improve the accuracy of magnetic resonance imaging (MRI) for predicting a complete response to neoadjuvant chemotherapy (NACT) for locally advanced breast cancer, research suggests.
Speaking to the press at the virtual AACR Annual Meeting 2021, presenting author Francesco Ravera, from the University of Genoa in Italy, said: “Finding a more accurate method [than MRI] for the assessment of complete response in axillary lymph nodes to neoadjuvant chemotherapy in patients affected by breast cancer may allow the omission of sentinel lymph node biopsy in complete responders, which could be replaced by longitudinal radiological monitoring.”
He added: “This would represent substantial progress in the pursuit of an effective, minimally invasive treatment of patients affected by breast cancer.”
Ravera and team used an automated electrophoresis device to measure the concentration of differently sized cfDNA fragments in plasma samples collected before surgery from 38 patients who had completed anthracycline or taxane-based NACT. Of these, 11 had a pathologic complete response (pCR) to treatment and 27 had an incomplete response.
The researchers then determined which cfDNA fragment sizes best predicted the response to NACT at post-surgery histopathologic examination and used them to create a normalized measure of cfDNA integrity, namely the cfDNA integrity index (DII), which was the ratio of fragments that were 321–1000 base pairs (bp) long to those 150–220 bp in length.
This index was used to build an explorative classifier for breast cancer response to NACT and compare its performance with that of MRI.
Ravera and co-authors reported in their poster that, at a cutoff above 2.71, the accuracy of the DII for the prediction of pCR was 81.6% in the 38 patients studied. By comparison, the accuracy of MRI in the same cohort was 77.1%.
The sensitivity and specify of DII for predicting pCR were 81.8% and 81.5%, respectively, while the corresponding values for MRI were 72.7% and 81.5%.
When the two techniques were combined the accuracy of pCR prediction reached 92.6% in cases where the two methods gave concordant outcomes (approximately 70% of cases). For these cases, the positive predictive value was 87.5% and the negative predictive value was 94.7%.
Ravera concluded: “Our work identifies a new parameter that is easily combinable with MRI for a more accurate prediction of response following neoadjuvant treatment, with possible implications for current protocols for the evaluation of nodal residual disease among patients with breast cancer undergoing neoadjuvant chemotherapy.”
He added: “Future work is needed to validate this new parameter to verify its utility for clinical practice.”
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