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Background: As outcomes improve in early-stage breast cancer, clinical trials are undergoing a paradigm shift from intensification trials (more therapy) to improve survival to optimization trials, which assess the potential for using less toxic therapy while preserving survival outcomes. However, little is known about physician perspectives in community and academic settings about possible barriers and facilitators that could impact accrual to optimization clinical trials and about the generalizability of future findings. Methods: We conducted a qualitative study with semi-structured interviews of medical oncologists from different academic and community practices to assess their perspectives on optimization trials. Interviews were audio-recorded and transcribed. Three independent coders utilized a content analysis approach to analyze transcripts using NVivo. Major themes and exemplary quotes were extracted. Results: Forty-six physicians were approached from 3/31/21-11/5/21; 39 oncologists from different oncology practices across 17 states completed interviews, 7 either declined or did not respond to email requests. Physician characteristics were balanced: men vs. women (49% vs 51%) and community oncologist vs. academic oncologist (49% vs 51%); and time practicing as medical oncologist (31% 0-9 years; 33% 10-19 years; 36% 20+ years). All 39 physicians reported that they would enroll patients in optimization clinical trials. Oncologists reported the need for treatment optimization, with one oncologist noting “historically, we’ve given way too much treatment to patients.” Oncologists highlighted specific reasons to consider optimization trials. They included quality of life improvement by reducing toxicity; reduction in financial toxicity; fertility preservation; ability to avoid chemotherapy; minimization of overtreatment in patients with comorbid conditions; personalized treatment; opportunities to test novel therapies; and leveraging the availability of targeted therapies. At the same time, there was hesitancy amongst some oncologists with this approach, “All my life I’ve worked to try to improve things and so I am not totally philosophically comfortable with the notion that I’m going to be happy with a result that says, we haven’t improved it but we can get by with less.” In addition, oncologists also identified accrual barriers, like tumor-specific biology, individual (host) factors (e.g. disease characteristics, patient demographics, patient psychological state, patient preferences), prognostic markers of risk, access to therapies, provider experience, and system constraints. They voiced recommendations regarding preliminary data, trial design, and tools to support communication about and enrollment in optimization trials. Conclusions: While optimization clinical trials are generally accepted to be beneficial by oncologists, barriers impact their acceptance. Scientifically robust design and education to overcome barriers are needed to support future enrollment on trials tailoring therapy based on risk and potential benefit to allow true personalization of treatment. Citation Format: Gabrielle B. Rocque, Andrews Courtney, Rachel M. Frazier, Lawhon Valerie, Stacey A. Ingram, Mary Lou Smith, Lynne I. Wagner, Lisa Zubkoff, Nadine Tung, Lauren P. Wallner, Antonio C. Wolff. Oncologist-reported Barriers and Facilitators to enrolling patients in optimization trials that test less intense cancer treatment [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 P6-09-04.

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.

Background: Being an oncologist means accepting that some patients will have disease recurrence despite the most expert treatments. The universality of that experience, however, does not negate the potential for decisional regret and emotional distress on the part of the physician. The broad scale movement towards treatment optimization in medicine likely complicates this experience, as enrollment in de-escalation clinical trials inevitably means that the patient will receive less than the current standard of care. The objective of this study was to assess physician perceptions of potential emotional distress and decisional regret following patient recurrence through exploring the broad range of factors that either moderate or exacerbate those experiences. Methods: Physicians who treat breast cancer in academic and community settings across the United States participated in a qualitative interview designed to assess physician perspectives regarding patient enrollment in de-escalation clinical trials. Purposive sampling techniques were utilized to construct a balanced sample (sex, time in practice) of 39 participants. A subsection of the interview schedule centered on the experiences of decisional regret and distress surrounding patient recurrence. Interviews were recorded, transcribed, and analyzed in order to identify shared themes. Two independent coders performed a content analysis, identifying and recording factors that impact the level of distress that the physician may feel. Results: Thirty-six physicians provided in depth responses regarding their experience when a patient recurs. A total of 21 factors that affected recurrence stress were identified and spanned broad categories including patient features, disease biology, the design of the clinical trial, and characteristics of the physician. All participants expressed willingness to enroll patients in de-escalation-focused clinical trials. However, approximately half of the sample indicated that the experience would be worse after enrollment in a de-escalation trial than after a traditional intensification trial, and a quarter admitted that patient recurrence after a de-escalation trial would impact their decision making regarding future patient enrollment. Individuals not likely to experience distress emphasized having a strong trial rationale, informed patient consent, and engaging in shared decision-making, while greater distress centered on the fear of “not doing enough” and the patient missing out on necessary treatment. Conclusions: Many factors contribute to the experience of physician decisional regret and emotional distress after patient recurrence. Although most physicians recognize the importance of de-escalation focused clinical trials, a significant proportion indicated a greater potential for distress following patient recurrence in such trials and offered insight into how trial design and the process of patient enrollment can be improved to minimize potential distress. Citation Format: Nicole L. Henderson, Andrews Courtney, Lawhon Valerie, Stacey A. Ingram, Lisa Zubkoff, Nadine Tung, Lynne Wagner, Lauren P. Wallner, Antonio C. Wolff, Gabrielle B. Rocque. "Clinical Trials are Space Travel": Moderators of Recurrence Stress among Breast Cancer Oncologists [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 P6-05-54.

Background: HMG-CoA reductase inhibitors (“statins”) have shown broad-spectrum anti-cancer properties in laboratory studies. In epidemiologic studies, statin use has been linked to reduced risk of advanced prostate cancer (PCa). We investigated whether statin use is associated with reduced risk of recurrence in PCa patients who received radical prostatectomy. Methods: All men with incident PCa diagnosed between 2004-2005 who subsequently underwent radical prostatectomy in Kaiser Permanente Southern California (KPSC) health plan were identified using KPSC's accredited cancer registry. Exclusion criteria included 0.2 ng/ml; and (2) clinical disease progression, defined as diagnosis of metastatic disease (identified using ICD-9 codes) or PCa-related death (i.e., PCa as primary cause of death). Information on statin use, demographics, co-morbid conditions, pathoclinical prognostic factors, e.g., stage and Gleason score, and outcomes were obtained from cancer registry and electronic medical records. The effects of statin use prior to and after prostatectomy were both examined using bivariate and multivariable Cox models, adjusting for known prognostic factors. For post-operative statin exposure, a time-dependent Cox model was used. Results: A total of 1192 men were included; 38% had pre-operative and 55% had post-operative statin use. Neither pre- nor post-operative statin use was associated with risk of any outcome, as there was no evidence of a clear dose-response relationship (Table). Conclusion: These data suggest that despite statin's protective effect in developing PCa, statin use may not prevent PCa progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 647. doi:1538-7445.AM2012-647