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William J. Gradishar, MD, FACP, FASCO


ASCO 2023: The Potential of ctDNA to Predict Future Relapse in a Subtype of Breast Cancer

By: Vanessa A. Carter, BS
Posted: Monday, June 5, 2023

The phase III PENELOPE-B trial, conducted by Nicholas C. Turner, MA, MRCP, PhD, of The Institute of Cancer Research, Royal Cancer Hospital, London, and colleagues, evaluated the potential of circulating tumor DNA (ctDNA) to predict relapse in patients with advanced estrogen receptor–positive, HER2-negative breast cancer who received 1 year of palbociclib with endocrine therapy after neoadjuvant chemotherapy. Their results, presented during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 502), appear to support that ctDNA detection after neoadjuvant chemotherapy and surgery may be associated with a high risk of early relapse.

“Testing ctDNA after recent neoadjuvant chemotherapy in luminal-A–like breast cancer has relatively low ‘sensitivity’ for predicting future relapse, in particular for later relapses, in part suggesting that response to neoadjuvant chemotherapy may reduce ctDNA detection,” the investigators stated.

A total of 129 patients in the PENELOPE-B trial were endocrine therapy–naive, and 78 had a baseline ctDNA sample analyzed. Plasma samples were collected after completion of neoadjuvant therapy and surgery (baseline), before cycle 7, at the end of treatment, and upon disease progression.

The median follow-up was 42.9 months, and ctDNA was associated with invasive disease–free survival in seven patients at baseline (P < .0001). Additionally, four patients had ctDNA detected at cycle 7, which also significantly correlated with invasive disease–free survival (P < .0001). Of note, two patients who had baseline ctDNA detection had undetectable ctDNA at cycle 7 and remained progression-free at 30 months; one patient later relapsed. Furthermore, three patients with detectable ctDNA at cycle 7 relapsed within 25 months. A total of 12 patients had distant relapse within 24 months, although 4 and 3 individuals had ctDNA detected at baseline and cycle seven7 or the end of therapy, respectively. Of eight patients with distant relapse after 24 months, two had ctDNA detected at baseline, but none were detected at later timepoints.

Disclosure: For full disclosures of the study authors, visit

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