1. Characterizing advanced breast cancer heterogeneity and treatment resistance through serial biopsies and comprehensive analytics
- Author
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Zahi Mitri, Marilyne Labrie, Laura M. Heiser, Carol Beadling, Brett Johnson, Allen G. Li, Joe W. Gray, Annette Kolodzie, Janice Patterson, George Thomas, Christopher L. Corless, Gordon B. Mills, Alexander R. Guimaraes, Jamie M. Keck, Molly Downey, Allison L. Creason, Swapnil Parmar, and Raymond C. Bergan
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Tumour heterogeneity ,Advanced breast ,medicine.medical_treatment ,Disease ,Article ,Targeted therapy ,03 medical and health sciences ,Breast cancer ,0302 clinical medicine ,Internal medicine ,Cancer genomics ,medicine ,Clinical significance ,RC254-282 ,Molecular medicine ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer ,medicine.disease ,Metastatic breast cancer ,030104 developmental biology ,Analytics ,030220 oncology & carcinogenesis ,business - Abstract
Molecular heterogeneity in metastatic breast cancer presents multiple clinical challenges in accurately characterizing and treating the disease. Current diagnostic approaches offer limited ability to assess heterogeneity that exists among multiple metastatic lesions throughout the treatment course. We developed a precision oncology platform that combines serial biopsies, multi-omic analysis, longitudinal patient monitoring, and molecular tumor boards, with the goal of improving cancer management through enhanced understanding of the entire cancer ecosystem within each patient. We describe this integrative approach using comprehensive analytics generated from serial-biopsied lesions in a metastatic breast cancer patient. The serial biopsies identified remarkable heterogeneity among metastatic lesions that presented clinically as discordance in receptor status and genomic alterations with mixed treatment response. Based on our study, we highlight clinical scenarios, such as rapid progression or mixed response, that indicate consideration for repeat biopsies to evaluate intermetastatic heterogeneity (IMH), with the objective of refining targeted therapy. We present a framework for understanding the clinical significance of heterogeneity in breast cancer between metastatic lesions utilizing multi-omic analyses of serial biopsies and its implication for effective personalized treatment.
- Published
- 2021