AACR II: ARTEMIS Trial of Neoadjuvant Systemic Therapy in Triple-Negative Breast Cancer
Posted: Monday, July 13, 2020
Based on the profiling results of the randomized ARTEMIS study presented during the American Association of Cancer Research (ACCR) Virtual Annual Meeting II (Abstract 1497/8), molecular profiling of longitudinal triple-negative breast cancer samples reveals distinct response patterns in tumors and their microenvironments upon treatment with doxorubicin-based chemotherapy. According to Sahil Seth, PhD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues, comprehensive molecular profiling of longitudinal biopsies, with an integrative evaluation of subclonal selection and changes in molecular pathways, may serve as a critical biomarker for chemotherapy and subsequent targeted therapy trials.
In total, 50 patients represented the initial cohort. They received four cycles of doxorubicin-based chemotherapy. Biopsies were performed before (mandatory) and after (optional) chemotherapy. Volumetric change by ultrasound at completion of chemotherapy or disease progression was calculated. Patients with sensitive disease received subsequent taxane-based therapy.
Predominately, tumors reacted to chemotherapy in four different patterns with variation in immune and EMT-related pathways, the investigators reported. Enrichment of epithelial-mesenchymal transition was associated with a poor prognosis and higher red blood cell count (pathologic complete response rates of 10.3% vs. 42%, P < .05). Multiple time points were leveraged to constrain subclonal clustering and enhance the accuracy of phylogenetic tree construction. Significant subclonal selection was detected in 22% of evaluable cases with biopsies before and after treatment. Analysis of the validation cohort is still underway.
“Integrative analysis of genomic and transcriptomic changes can lead to better stratification of the response to neoadjuvant systemic therapy,” the investigators proposed.
Disclosure: For full disclosures of the study authors, visit abstractsonline.
