Related Experiment Video
Updated: Jun 25, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Use of Next-Generation Sequencing for Highly Endocrine-Sensitive Metastatic Breast Cancer to Inform Late-Phase
Leyla Bayat1, Margaret McCabe2, Sergey Cherneykin3
1Department of Medicine, New York-Presbyterian Westchester/Columbia University Medical Center, Bronxville, NY, USA.
Introduction:
Biomarker profiling has long been a cornerstone in the treatment of both early-stage and metastatic breast cancer. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression continues to form the foundation of our understanding of breast cancer prognosis and optimal treatment. Over the past decade, next-generation sequencing (NGS) has expanded our capacity to prevent disease progression through new mutational targets.
Case Presentation:
We present the case of a postmenopausal woman who, 12 years after initial diagnosis with locally advanced ER+, PR+, and HER-2- breast cancer, developed recurrent metastatic disease. Control of disease progression over the following 15 years was attained through her cancer's uniquely prolonged sensitivity to endocrine therapy and, later in her disease course, by the discovery of multiple targetable mutations through NGS. She had a sustained response to both the inhibition of PIK3CA and, later, the inhibition of ESR1. Repeat NGS late in her treatment revealed new NRG1 NTRK fusion and KRAS G12C mutations. Our patient succumbed to her disease before subsequent targeted therapy could be initiated.
Conclusion:
Our patient's treatment course was significantly influenced by repetitive NGS informing her treatment with novel targeted therapies, with detection of emerging actionable mutations rarely seen in breast cancer toward the end of her life. This observation highlights the potential clinical benefit of repeating NGS even in late stages of breast cancer treatment. Furthermore, NGS may expand our ability to utilize targeted agents in not only early phase but also later phase breast cancer treatment.
