Abstract PS1-06-01: Predictive Value of Breast-Specific Gamma Imaging for Pathologic Response and Prognosis in Early Breast Cancer After Neoadjuvant Therapy: A Prospective Trial

Abstract Background: Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer. Achieving a pathologic complete response (pCR) is strongly associated with favorable long-term outcomes. However, current imaging modalities, such as magnetic resonance imaging (MRI), have limitations in quantifying residual metabolic activity following NAC. Breast-specific gamma imaging (BSGI) provides functional assessment through the tumor-to-normal ratio (TNR), with established diagnostic value in prior studies. Prospective validation of TNR's predictive value for pCR and survival outcomes is currently lacking. This study aims to evaluate whether post-NAC TNR can identify patients with chemo-sensitive tumors and a superior prognosis. Methods: This single-center prospective trial (NCT02556684) enrolled 137 patients with stage I-III breast cancer who received standard NAC followed by surgery between 2014 and 2023. Inclusion criteria required patients to have clinical stage T1-4 and N0-3, baseline biopsy-confirmed invasive carcinoma, and completion of the planned NAC regimen. Exclusion criteria were bilateral or metastatic disease or incomplete NAC. Breast-specific gamma imaging was performed after 2 cycles of NAC using 99mTc-sestamibi (MIBI) and dual-head gamma cameras. The tumor-to-normal ratio (TNR) was calculated as the maximum tumor uptake divided by the mean uptake in the contralateral breast parenchyma. The primary endpoints were pathological complete response (pCR) and 3-year disease-free survival (DFS). Statistical analyses included χ2 tests for associations, Kaplan-Meier analysis with log-rank tests for survival comparisons, and multivariate Cox regression models adjusted for clinicopathologic covariates. Results: Baseline characteristics were balanced between groups for age, nodal status, grade, and Ki-67 (p0.05), though TNR-low patients had significantly higher HER2+ subtype prevalence (65% vs. 46%, p = 0.026). TNR-low was strongly associated with pathologic complete response (pCR), with 34.8% achieving pCR versus 14.7% in TNR-high group. Survival analysis demonstrated significantly improved disease-free survival (DFS) for TNR-low patients after median follow-up of 42.5 months. DFS benefits were consistently observed in the overall population and key clinical subgroups: overall cohort (hazard ratio HR = 0.33, 95% confidence interval CI:0.14-0.81, p = 0.002), HR+HER2- (HR = 0.23; 95% CI:0.07-0.73; p = 0.001), HER2+ (HR = 0.23; 95% CI:0.04-1.48; p = 0.009), pCR patients (HR = 0, p = 0.016), and non-pCR patients (HR = 0.42; 95% CI:0.18-1.00; p = 0.02). The triple-negative subgroup showed non-significant trends likely due to limited sample size (n = 19). TNR demonstrated independent prognostic value in multivariate Cox regression. After adjusting for established factors (including pCR status, T stage, nodal stage, Grade and Ki-67 index), TNR-low status confirmed as a significant predictor of superior disease-free survival (DFS), with a hazard ratio of 0.43 (95% CI: 0.20-0.93; p = 0.031). Notably, TNR demonstrated predictive capacity beyond pathologic complete response. No endpoint events occurred in TNR-low/pCR patients, whereas TNR-low/non-pCR patients had 58% lower risk of recurrence versus TNR-high/non-pCR patients. Conclusion: These results establish TNR as a robust imaging biomarker which serves as a valuable complement to current assessment methods. The prospective design and consistent survival benefit across multiple subgroups support clinical integration of BSGI-derived parameters to guide post-neoadjuvant risk stratification, potentially enabling therapy escalation for TNR-high/non-pCR patients and de-escalation strategies for TNR-low/pCR patients. Citation Format: T. Qian, X. Ye, Y. Wu, L. Pang, L. Li, X. Yu, Z. Wang, J. Huang. Predictive Value of Breast-Specific Gamma Imaging for Pathologic Response and Prognosis in Early Breast Cancer After Neoadjuvant Therapy: A Prospective Trial abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-06-01.