Abstract PO5-17-03: Relative Dose Intensity and Protraction of Neoadjuvant Chemotherapy in Early-Stage and Locally Advanced Breast Cancer: A collaborative multicenter analysis in Colombia
Authors: Murillo Alejandro , Acevedo Andres , Betancur Santiago , Borras-Osorio Mariana , Munevar Isabel , Mantilla William , Pino Luis 
Published: May 2024

Abstract
Introduction: Breast cancer (BC) is the most frequent neoplasm in Colombia. In contrast to high-income countries, the expected 5-year overall survival (OS) remains below 80% over the last years. Neoadjuvant chemotherapy (NACT) has reduced the risk of relapse and death by achieving higher pathological complete response (ypCR) rates, but delays and dose reductions could impact prognosis negatively. We have previously reported the outcomes of NACT from a real-world multicenter historical cohort of Colombian early and locally advanced BC patients. We aimed to analyze NACTRelative Dose Intensity (RDI) and protraction data as related to clinical outcomes in the same cohort. Methods: We performed a secondary analysis of the primary database of 312 BC patients treated with NACT where ypCR rate was 34·6%, with 88·2% 5-year OS. We considered RDI and protraction as independent variables for the same outcomes. The RDI was estimated using the Hrynuik method, and protraction was defined as the difference between planned and actual completion time for the NACT exceeding 7 days from standard 21-day cycles. Chemotherapy regimens are based on the National Hematology and Oncology Association (ACHO) guidelines. We excluded cases with missing or conflicting data. Univariate, and bivariate analysis, and partition survival trees were performed to examine variable interactions. Results: From the original cohort of 312 patients, 47 and 7 additional patients were excluded due to missing protraction and RDI data, respectively; the final analysis included 261 and 254 patients, respectively. The average days to complete planned chemotherapy cycles were 154,4 (SD 32,29 days). 203 patients (77,8%), 26 patients (10%), and 11 patients (4,2%) received complete 8,7 and 6 NACT cycles, respectively. Overall, 175 patients (67%) had protracted chemotherapy cycles, being highest in the 7-cycle subgroup (77%). 169 patients (66,5%) had a dose intensity over 85% and 90 patients (35.43%) achieved an RDI of 100% or more. The mean RDI for the cohort was 79,8% (SD 19,91%) and it differed according to expression profile subgroups in decreasing order as follows: HER2 pure 98,85% (SD 19,59%), Luminal A 96,03% (SD 21,28%), Triple Negative 97,81% (SD 19,73%), Luminal B HER+ and HER2- being lowest with 90,43% (SD 19,47%) and 87,75% (SD 23,22%), respectively. Neither NACT RDI nor protraction was associated significantly with ypCR, conservative surgery, or all-cause OS. Although statistically not-significant, sensitivity analysis through different RDI thresholds (20%-100%) demonstrated improved discriminatory capacity over ypCR for RDI &gt;= 85%. Conclusion: On average, NACT-RDI greater than 85% was observed in Colombian patients with early and locally advanced BC similar to other cohorts. However, it was not associated with ypCR, conservative surgery, or OS. Also, NACT protraction beyond 7 days did not adversely affect clinical outcomes. However, this conclusion is limited due to the retrospective nature and loss of real-world data. Adverse events and their impact on RDI were not analyzed either. Further research is warranted to understand RDI's impact on clinical outcomes, and a large-scale trial is proposed to validate these findings.
Citation Format: Alejandro Murillo, Andres Acevedo, Santiago Betancur, Mariana Borras-Osorio, Isabel Munevar, William Mantilla, Luis Pino. Relative Dose Intensity and Protraction of Neoadjuvant Chemotherapy in Early-Stage and Locally Advanced Breast Cancer: A collaborative multicenter analysis in Colombia [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 PO5-17-03.