A retrospective study validated histological grade and Ki67 index as predictors of chemotherapy sensitivity in patients with intermediate-risk luminal breast cancer without lymph node metastases in a Chinese population (Huizhou Hospital, 2015–2022). After propensity score matching (196 cases), multivariate analysis showed as independent risk factors for disease-free survival (DFS): histological grade 2–3 (HR=5.398, p=0.028), Ki67 ≥20% (HR=5.020, p=0.012) and absence of chemotherapy (HR=3.998, p=0.DFS). Chemotherapy significantly reduced the risk of recurrence in Ki67 ≥20% (6.5% vs. 34.9%, p=0.003) and in grade 2–3 (7.1% vs. 35.6%, p=0.007), but not in grade 1. For overall survival (OS), only Ki67 ≥20% (HR=9.301, p=0.035) was an independent factor, without statistically significant benefit of chemotherapy (p=0.085). The model offers cost-effective guidance for chemotherapy decision-making in resource-limited settings.