Conference Coverage

Cell-free DNA improves response prediction in breast cancer



Combining plasma cell-free DNA (cfDNA) assessment with MRI improves prediction of pathological complete response to neoadjuvant chemotherapy in locally advanced breast cancer, according to researchers.

When the two techniques were in agreement, the accuracy of response prediction was 92.6% in the study, with a predictive value for complete response of 87.5% and a predictive value for absence of complete response of 94.7%, which was substantially better than either method alone.

“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,” researcher Francesco Ravera, MD, PhD, of the University of Genoa (Italy), said in a press release.

Dr. Ravera and colleagues presented their research in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract LB063).

Accurate response prediction is important because it guides subsequent surgical management, Dr. Ravera and colleagues noted. Pathological complete responders – generally about 25% of patients after neoadjuvant therapy – typically undergo a sentinel lymph node biopsy to ensure cancer hasn’t spread, while incomplete responders often have a complete axillary lymph node dissection.

Response is currently assessed by MRI, but accuracy is suboptimal, the researchers noted. A more accurate method might “allow the omission of sentinel lymph node biopsy in complete responders, which could be replaced by longitudinal radiologic monitoring. This would represent substantial progress in the pursuit of an effective, minimally invasive treatment,” Dr. Ravera said.

He and his colleagues turned to plasma cfDNA because it has shown potential for providing useful diagnostic, recurrence, and treatment response information in neoplastic patients.

When healthy cells die, they release similarly sized DNA fragments into the blood, but cancer cells release fragments of varying sizes. The heart of the research was using electrophoresis to assess the degree of fragmentation – called cfDNA integrity – in plasma samples from 38 patients after anthracycline/taxane-based regimens.

The researchers compared how well cfDNA, preoperative MRI, and the combination of the two methods predicted response according to surgical histology.

A total of 11 patients had pathological complete responses to neoadjuvant therapy.

The ratio of large 321-1,000 base pair sized fragments to smaller 150-220 base pair sized fragments, which the team dubbed the “cfDNA integrity index,” best predicted response. At a cutoff above 2.71, the index was 81.6% accurate in predicting pathological complete response, with a sensitivity of 81.8% and specificity of 81.5%.

The predictive power wasn’t much better than MRI, which was 77.1% accurate, with a sensitivity of 72.7% and a specificity of 81.5%.

The two techniques were concordant in their prediction in over two-thirds of patients. When the techniques agreed, accuracy was over 90%.

Prospective studies are needed to evaluate the cfDNA integrity index in combination with MRI, the researchers concluded.

The study was sponsored by the University of Genoa and others. Dr. Ravera disclosed no conflicts of interest.

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