In a study (PREDICT-DNA) reported in the Journal of Clinical Oncology, Hunter et al found that an ultrasensitive assay for circulating tumor DNA (ctDNA) to detect measurable residual disease after neoadjuvant therapy in patients with breast cancer did not distinguish pathologic complete response (pCR) from no pCR, but did provide important prognostic information.
Study Details
In the U.S. multicenter study (enrollment between 2016 and 2018), 227 patients with stage II to III HER2-positive or triple-negative breast cancer who received neoadjuvant therapy had ctDNA measured by an ultrasensitive assay (< 100 parts per million) at baseline, after neoadjuvant therapy and before surgery, and after surgery. The primary objective of the study was to assess whether the negative predictive value (NPV) of post–neoadjuvant therapy ctDNA for pCR was ≥ 90%. A secondary outcome measure was the association of ctDNA and invasive disease–free survival among patients with triple-negative breast cancer.
Key Findings
Among 227 patients, 220 were evaluable for pCR; of these, 52% had triple-negative breast cancer and 48% had HER2-positive disease. Among 220 evaluable patients, 91 (41%) had pCR after neoadjuvant therapy. All patients with pCR were ctDNA-negative; however, 40% of patients without pCR were also ctDNA-negative, yielding an NPV of 60% (95% confidence interval [CI] = 50%–69%).
Detectable ctDNA after neoadjuvant therapy was associated with increased risk of recurrence, irrespective of pCR achievement (hazard ratio [HR] = 8.9, 95% CI = 1.92–41.1, P = .005); detectable ctDNA after surgery was associated with a very high recurrence risk (HR = 128, 95% CI = 15–1,083, P < .001).
Among patients with triple-negative breast cancer, 3- and 5-year invasive disease–free survival rates among patients who were ctDNA-positive vs ctDNA-negative after neoadjuvant therapy were 57% vs 95% and 57% vs 92%, respectively (HR = 8.9, 95% CI = 2.4–33.0, P = .001).
The investigators concluded: “In HER2-positive breast cancer and triple-negative breast cancer, ctDNA after neoadjuvant therapy does not discriminate pCR from non-pCR. However, ctDNA provides markedly superior prognostic stratification, identifying patients with exceptional outcomes and those at extreme risk. These findings support ctDNA-guided therapeutic de-escalation and escalation strategies.”
Ben Ho Park, MD, PhD, of Vanderbilt University Medical Center, Nashville, Tennessee, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the Susan G. Komen Breast Cancer Foundation, Breast Cancer Research Foundation, and others. For full disclosures of the study authors, visit ascopubs.org.
