MCM2 expression in locally advanced hormone receptor–positive HER2 negative (HR+/HER2-) early breast cancer receiving neoadjuvant chemotherapy.

Abstract

e12532 Background: Mini-chromosome maintenance 2 (MCM2), a protein regulating the initiation of DNA replication, is associated with a high proliferative index and worse clinical outcomes in various cancer types, including breast cancer. MCM2 expression was shown to be more sensitive than Ki-67 in predicting prognosis in lung, head and neck, and thyroid cancer. In contrast to Ki-67, MCM2 is more readily expressed and may provide better prognostic and predictive information in luminal breast cancer. This study aimed to evaluate MCM2 expression in pre-neoadjuvant chemotherapy (NACT) specimens from patients with locally advanced HR+/HER2- breast cancer and its association with tumor response and clinicopathological factors. Methods: Stage 2-3 HR+/HER2- early breast cancer patients who received NACT followed by surgery between January 1, 2015, and December 31, 2020, at KCMH were retrospectively reviewed. MCM2 antibody (rabbit polyclonal, HPA 031496, dilution 1/200, Sigma Aldrich) was used for immunostaining of pre-NACT specimens with scoring by image analysis. NACT response in surgical specimens was assessed with RCB index. The relationship of MCM2 expression with clinicopathologic factors and RCB 0/I response after NACT were evaluated with univariate and multivariate analysis. ROC analysis was performed to identify the optimum MCM2 cut-off for RCB 0/I. Results: 72 patients with locally advanced HR+/HER2- who received NACT were evaluated. The median age was 50 years (ranges 26-80), and 71% of patients had stage 3. RCB 0/I responses were observed in 5 patients (6.9%). MCM2 ≥ 40% was significantly associated with RCB 0/I (OR = 18.3, 95% CI 1.88-178.98, p = 0.012) in univariate analysis. In contrast, Ki-67 expression was not associated with RCB 0/I at any cutoff point. The mean MCM2 expression was numerically higher in patients with RCB 0/I (39.3 ± 7.5 vs. 24.6 ± 2, p = 0.06). In the ROC analysis for predicting RCB 0/I with MCM2 expression, AUC was 0.75 (95% CI 0.51-0.99, p=0.04) with the optimum cut-off of ≥40% (sensitivity 80% and specificity 82%). MCM2 expression ≥ 40% was associated with unfavorable clinical pathological features, including histologic grade 3, ER <10%, PR negativity, and Ki-67 ≥ 20%. Patients with both baseline Ki67 ≥ 20% and MCM2 ≥ 40% had a trend toward worse 1-year recurrence-free survival (98% vs. 86%, p=0.06). Conclusions: High baseline MCM2 expression (≥40%) is associated with a higher chance of achieving RCB 0/I in locally advanced HR+HER2-breast cancer, unlike Ki67. Assessing MCM2 expression may provide additional prognostic and predictive information for HR+/HER2-breast cancer patients receiving neoadjuvant chemotherapy.