Abstract P6-01-04: The Hierarchy of Biomarkers

Abstract Background: Biomarkers with robust analytical and clinical validity can help optimize therapy decisions within clinical trials for patients with breast cancer, particularly if some data on clinical utility also exist. However, little is known about how physicians enrolling in clinical trials view them. Physician comfort with the integral use of conventional and investigational biomarkers for reducing chemotherapy intensity within clinical trials is explored in this study. Method: A convenience sample of academic and community oncologists from across the United States were invited to participate in qualitative interviews that explored their perspectives on the use of biomarkers for the de-escalation of chemotherapy in patients with breast cancer. Purposive sampling techniques were used to identify participants, ensuring even distribution of gender, work setting, and time practicing medical oncology. Interviews were audio-recorded and transcribed. Transcripts were analyzed by two independent coders to identify major themes and exemplary quotes in NVivo. A framework for understanding how providers conceptualize biomarkers was created. Results: There was a total of 39 physicians with a median age of 50; 51% of physicians were academic and 49% were community-based. 44% of oncologists have been in practice for less than 15 years, and 36% and 20% of oncologists were in practice for 15-30 years and over 30 years, respectively. The model on physician level of comfort for biomarker use consisted of 1) standard of care biomarkers, 2) standard biomarkers in newer contexts, and 3) experimental biomarkers with inclusion of additional related subthemes. There was a shared theme among physicians that historical experience with a biomarker made them more comfortable in de-escalation of chemotherapy. The greatest level of physician comfort with biomarker for de-escalation of chemotherapy came with biomarkers used in standard of care (e.g., MammaPrint, Oncotype DX). Themes related to these biomarkers included: strong level of evidence, agreement with NCCN guidelines, and widespread use in the community. For example, one physician stated, “for me to use a prognostic biomarker … typically it’s going to have to at least be within the NCCN guidelines or out there”. Secondly, physicians expressed reasonable confidence with some reluctance in the use of standard of care biomarkers in contexts that differ from where they were initially tested (i.e., use of biomarker in patients with different features or disease biology). These themes included the use of biomarkers in specific subtypes of cancer and when there is less supportive evidence. One physician commented, “It’s just hard to analyze and really know whether [pathCR in ER+ setting] actually holds like it does for other tumor biologies”. There was more hesitation and least comfort with experimental biomarkers (e.g., tumor-infiltrating lymphocytes, circulating tumor DNA). For experimental biomarkers, physicians were primarily concerned with the quality and quantity of evidence supporting their use. Prospective trials were favored over retrospective; however, physicians were accepting if the retrospective study included a large sample, other biomarkers were used in conjunction, or multiple studies confirmed the results. Other themes that emerged regarding experimental biomarkers were their testing in diverse populations and reproducibility. Physicians expressed contentment with experimental biomarkers that were proven in “multiple big enough studies”, were “reproducible and not subjective”, and “demonstrate utility in the patient population that’s relevant”. Conclusion: Biomarkers can be divided into 3 successive levels: 1) standard of care biomarkers, 2) standard biomarkers in newer contexts, and 3) experimental biomarkers. Level of comfort concerning the use of biomarkers for de-escalation of chemotherapy is related to level of evidence for experimental biomarkers. Citation Format: Noon Eltoum, Halle thannickal, Nicole L. Henderson, Lynne I. Wagner, Lauren P. Wallner, Antonio C. Wolff, Gabrielle B. Rocque. The Hierarchy of Biomarkers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-04.