American Association for Cancer Research Annual Meeting

American Association for Cancer Research Annual Meeting

Issue: May 25, 2021
Perspective from Kristen Whitaker, MD, MS
Source:

Cirmena G, et al. Abstract LB063. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

Disclosures: Ravera reports no relevant financial disclosures. Please see the abstract for all other researchers’ relevant financial disclosures.
April 10, 2021
3 min read
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Liquid biopsy may improve presurgical assessment of locally advanced breast cancer

Issue: May 25, 2021
Perspective from Kristen Whitaker, MD, MS
Source:

Cirmena G, et al. Abstract LB063. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

Disclosures: Ravera reports no relevant financial disclosures. Please see the abstract for all other researchers’ relevant financial disclosures.
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Plasma cell-free DNA integrity assessed prior to surgery accurately predicted achievement of pathologic complete response to neoadjuvant chemotherapy among patients with locally advanced breast cancer, according to study results.

The findings, presented at the virtual American Association for Cancer Research Annual Meeting, also showed potential for combining this liquid biopsy approach with MRI to improve prediction of pathologic complete response in this group.

Accuracy of predicting pathologic complete response to neoadjuvant chemotherapy in locally advanced breast cancer
Data were derived from Cirmena G, et al. Abstract LB063. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

After receiving neoadjuvant chemotherapy, patients with locally advanced breast cancer are assessed for response to guide the appropriate course of surgery. MRI typically is used for this assessment, despite its “suboptimal accuracy,” Francesco Ravera, MD, PhD, fellow in the department of internal medicine at University of Genoa in Italy, told Healio.

Francesco Ravera, MD, PhD
Francesco Ravera

“This impacts the surgical management of patients affected by breast cancer, in particular regarding lymph node disease assessment,” he said. “Whereas patients presenting with residual disease in lymph nodes at radiology directly undergo extensive axillary dissection, complete responders require sentinel lymph node biopsy. An accurate way to effectively assess the achievement of pathologic complete response to the systemic treatment may allow us to spare complete responders from sentinel lymph node biopsy, avoiding their exposure to possible side effects of this procedure.”

Ravera and colleagues evaluated whether an electrophoresis-based method for assessment of plasma cell-free DNA integrity could be used to evaluate response to neoadjuvant chemotherapy among patients with breast cancer.

The analysis included data of 62 patients undergoing anthracycline- or taxane-based neoadjuvant chemotherapy followed by surgery. Researchers collected plasma samples from the patients at diagnosis, after anthracycline administration and after completion of neoadjuvant chemotherapy but prior to surgery.

Researchers evaluated the plasma samples for integrity of cell-free DNA based on the knowledge that low cell-free DNA integrity, which corresponds to high cell-free DNA fragmentation, is associated with neoplasms. They used automated electrophoresis (2200 TapeStation, Agilent) to characterize the concentration of the cell-free DNA fragments as 90 base pairs (bp) to 150 bp, 150 bp to 220 bp, 221 bp to 320 bp, 100 bp to 300 bp and 321 bp to 1,000 bp.

Researchers conducted cell-free DNA fragmentation profiling on samples taken after completion of neoadjuvant chemotherapy from 38 patients, which they matched with results of postsurgical histopathological examinations.

Eleven of 38 patients experienced pathologic complete response to neoadjuvant chemotherapy, whereas the other 27 had an incomplete response with evidence of residual disease in the breast or axillary nodes, for a 30/70 ratio of response to nonresponse.

Researchers selected a normalized measure of cell-free DNA integrity — expressed as a ratio of the concentration of 321 bp to 1,000 bp sized fragments to the concentration of 150 bp to 200 bp sized fragments — that appeared most predictive of response to neoadjuvant chemotherapy.

Researchers used this ratio to form the cell-free DNA integrity index — for which values of 2.71 or greater were associated with the achievement of pathologic complete response, whereas values less than 2.71 were associated with incomplete response — which they used to build an explorative classifier to predict response. Through bootstrapped logistic regression, they compared the performance of this classifier with MRI in predicting response to neoadjuvant chemotherapy.

MRI demonstrated an accuracy of 77.1% in predicting pathologic complete response, with a sensitivity of 72.7% and specificity of 81.5%, whereas the cell-free DNA integrity index showed an accuracy of 81.6%, a sensitivity of 81.8% and specificity of 81.5%.

When combining MRI with the cell-free DNA integrity index, in cases where the techniques were concordant, overall accuracy increased to 92.6%, with a positive predictive value of 87.5% and a negative predictive value of 94.7%.

These data show “great potential” in the use of cell-free DNA integrity to assess response to neoadjuvant chemotherapy, but the study is limited by its small sample size, according to Ravera.

“Sample size expansion is required to assess the effective accuracy of cell-free DNA integrity and its combination with MRI in the prediction of the response to systemic treatment,” he told Healio. “Moreover, the study of the biological bases underlying the alteration of cell-free DNA integrity in neoplastic patients would be of interest, possibly having implications for other clinical purposes.”