Abstract PO4-03-11: Discerning the impact of ctDNA detection on patient decisions in early-stage breast cancer
Authors: Ballinger Tarah , Zimet Gregory , Railey Elda , Smith Mary Lou , Schneider Bryan 
Published: May 2024

Abstract
Background: Detection of circulating tumor DNA (ctDNA) after neoadjuvant therapy for triple negative breast cancer (TNBC) is associated with increased risk of recurrence. Ongoing trials aim to determine whether knowledge of specific genomic mutations in ctDNA can inform targeted adjuvant therapy to improve prognosis. The impact of knowledge of ctDNA status on patient treatment decisions weighing benefit and toxicity is unknown.
Methods: 401 women were recruited via the Research Advocacy Network from Young Survivors’ Coalition, Living Beyond Breast Cancer, and Pink-4-Ever Ending Disparities. Participants had to self-report a history of non-metastatic breast cancer and have received chemotherapy in the prior 6 months to 10 years to be eligible. Participants completed a 27 question Qualtrics survey detailing demographics and experience with prior chemotherapy. Based on estimations from prior data, participants were presented with scenarios mimicking residual TNBC and unknown, negative, or positive ctDNA status with corresponding risk of recurrence of 40%, 20%, or 55% respectively. Participants were then presented with 12 scenarios (in random order) combining various degrees of absolute risk reduction (5%, 15%, 35%) with established toxicity profiles of four possible post-neoadjuvant therapies (capecitabine, immunotherapy, PARP inhibitor, and PI3K inhibitor). Participants rated scenarios in terms of acceptability from 0-100. A general linear model with repeated measures (3 × 4) was used to determine the contributions of risk reduction and toxicity to acceptability. Models were also run with the addition of between subject factors: age group (&lt; 40; &gt;40), stage of cancer (Stage 1; Stage 2/3), and previous experience with toxicity (Yes; No), to examine whether any of these factors moderated the effects of risk reduction and toxicity. Effect sizes were determined by partial h2.
Results: 286 eligible respondents completed the survey with evaluable responses. Average age was 41.2 (range 27-75). When the hypothetical risk of recurrence decreased from 40% (ctDNA-unknown) to 20% (ctDNA-negative), significantly less participants preferred adjuvant capecitabine vs. no therapy (95.1% versus 63.3%, p&lt; 0.001). Across the 12 scenarios, both benefit (F=448.5, p&lt; 0.001; preference for greater benefit) and toxicity (F=33.64, p&lt; 0.001; preference for lower toxicity) significantly influenced acceptability, but benefit had a much larger effect size than toxicity (h2=0.76 and 0.26, respectively). There was no significant interaction effect, and the pattern of results was not moderated by age, stage of cancer, or prior experience with chemotherapy toxicity. The most preferred scenario (greatest benefit, lowest toxicity) had a mean rating of 87.8/100; however, even when presented with the scenario with the lowest benefit and highest toxicity, the mean rating was still 31.5/100, suggesting that this combination would be acceptable to some individuals.
Conclusions: Knowledge of ctDNA-negative status significantly reduced the number of participants preferring adjuvant capecitabine over no further therapy. When faced with ctDNA-positive status, participants preferred maximum risk reduction regardless of toxicity profile. As genomic technology advances, it is imperative that researchers and treating physicians understand its impact on patient decision making.
Citation Format: Tarah Ballinger, Gregory Zimet, Elda Railey, Mary Lou Smith, Bryan Schneider. Discerning the impact of ctDNA detection on patient decisions in early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-11.