Prognostic Implications of Magee Equation 3 and Residual Cancer Burden in patients receiving Neoadjuvant Chemotherapy for HR-Positive HER2-Negative Breast Cancer.

Abstract

Breast cancer (BC) presents significant molecular heterogeneity, complicating prognosis and treatment strategies. While molecular testing enhances our understanding of BC, high costs can limit accessibility in certain healthcare settings. This retrospective cohort study evaluates the prognostic value of Magee Equation 3 (ME3) and Residual Cancer Burden (RCB) in patients with HR-positive, HER2-negative BC treated at the Instituto do Câncer do Estado de São Paulo from January 2011 to January 2024. We included 203 women, with a mean age of 50.2 years, diagnosed with HR-positive, HER2-negative BC (stages I-III), who completed neoadjuvant chemotherapy (NAC) followed by surgery. ME3 scores were categorized as low (<18), intermediate (18-25), and high (>25), while RCB was classified into four groups (0, 1, 2, or 3). Associations between ME3 and RCB categories were analyzed using chi-square and Cochran-Mantel-Haenszel tests. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method with log-rank tests. Prior to NAC, 60.1% of patients had tumors >5 cm, 69.5% had positive lymph nodes, and 85.7% had invasive carcinoma of non-special type, with a mean Ki67 index of 35.5%. Analysis revealed that 22.2% of patients had ME3 > 25, 39.9% had ME3 18-25, and 37.9% had ME3 < 18. A significant inverse association was found between RCB and ME3 (p<0.0001). At a median follow-up of 91.4 months (range: 8-157 months), significant associations were noted for OS (log-rank p=0.0059) and DFS (log-rank p=0.0028) with ME3 categories; patients with low ME3 showed better outcomes. In patients with RCB-3, those with ME3 < 18 had a lower risk of recurrence compared to those with ME3 18-25 (HR: 4.70, 95% CI 2.00-11.02; p = 0.0004) and ME3 > 25 (HR: 5.18, 95% CI 1.85-14.15; p = 0.0017). Similarly, lower risks of death were observed for ME3 < 18 versus higher ME3 categories. In conclusion, ME3 significantly correlates with OS and DFS, suggesting it may serve as a valuable alternative to molecular assays in resource-limited settings. Combining ME3 with RCB enhances individualized risk stratification, providing a more precise prognostic assessment for patients with high RCB.