Prognostic Implications of Magee Equation 3 and Residual Cancer Burden in Patients Receiving Neoadjuvant Chemotherapy for Hormone Receptor-Positive HER2-Negative Breast Cancer

Abstract

Breast cancer (BC) presents significant molecular heterogeneity, complicating prognosis and treatment strategies. Although molecular testing enhances our understanding of BC, high costs can limit accessibility in certain health care settings. This retrospective cohort study evaluates the prognostic value of Magee equation 3 (ME3) and residual cancer burden (RCB) in patients with hormone receptor-positive, human epidermal growth factor receptor 2-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 hormone receptor-positive, human epidermal growth factor receptor 2-negative BC (stages I-III), who completed neoadjuvant chemotherapy followed by surgery. ME3 scores were categorized as low (<18), intermediate (18-25), and high (>25), whereas RCB was classified into 4 groups (0, 1, 2, or 3). Associations between ME3 and RCB categories were analyzed using χ² 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 neoadjuvant chemotherapy, 60.1% of patients had tumors >5 cm, 69.5% had positive lymph nodes, and 85.7% had invasive carcinoma of nonspecial 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 < .0001). At a median follow-up of 91.4 months (range: 8-157 months), significant associations were noted for OS (log-rank P = .0059) and DFS (log-rank P = .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 with those with ME3 18-25 (hazard ratio: 4.70, 95% CI: 2.00-11.02; P = .0004) and ME3 > 25 (hazard ratio: 5.18, 95% CI: 1.85-14.15; P = .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 that 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.