Liang Cheng, President of International Society of Urological Pathology, Vice Chair for Translational Research at the Warren Alpert Medical School of Brown University, shared a post on LinkedIn:
“Happy Fourth of July! Honored to share this important study published in the July 2026 issue of Laboratory Investigation by Drs. Liu Liu, Stephanie Graff, and
Yihong Wang.
This investigation provides important biologic insights and clinical perspectives for the management of HR-positive/HER2-negative metastatic breast cancer through integrated genomic profiling of paired tumor tissue and circulating tumor DNA (ctDNA). The study demonstrates that liquid biopsy is highly effective for detecting actionable ESR1 and PIK3CA mutations and monitoring treatment-emergent resistance. We also identify a previously underrecognized subgroup of patients harboring ESR1 amplifications, detectable only by tissue comprehensive genomic profiling. These amplifications frequently co-occur with CCND1 and FGFR1 amplifications, suggesting potential mechanisms of resistance to CDK4/6 inhibitors and highlighting the continued importance of tissue-based molecular profiling.
Importantly, the study also shows that TP53 alterations detected exclusively in ctDNA may represent clonal hematopoiesis rather than tumor-derived mutations, emphasizing the need for careful interpretation of liquid biopsy results. Together, these findings underscore the complementary strengths of tissue and liquid biopsy and support an integrated molecular testing strategy to improve patient selection, guide precision therapy, and enable real-time monitoring of treatment resistance in advanced breast cancer.”
Title: Paired Tissue and Circulating Tumor DNA Profiling Reveals Novel ESR1 Amplifications and CDK4/6 Inhibitor Resistance Mechanisms in Hormone Receptor–Positive/HER2–Negative Metastatic Breast Cancers
Authors: Liu Liu, Stephanie L. Graff, Liang Cheng, Yihong Wang
Read the Full Article.
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