Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate relapse for patients with the major subtypes of breast cancer as classified using immunohistochemical assay and to investigate the patterns of benefit from the therapies over the past years. The study population included primary, operable 2,118 breast cancer patients, all non-specific infiltrative ductal carcinoma, with the median age of 53.2 years. All patients underwent local and/or systemic treatments. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. The expression of estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 were analyzed by immunohistochemistry. All patients were classified into the following categories: luminal A, luminal B, HER2 overexpressing, basal-like, and unclassified subtypes. Ki-67 was detected in luminal A subtype. The median follow-up time was 67.9 months. Luminal A tumors had the lowest rate of relapse (12.7%, P < 0.001), while luminal B, HER2 overexpression, and basal-like subtypes were associated with an increased risk of relapse (15.7, 19.1, 20.9%). Molecular subtypes retained independent prognostic significance (P < 0.001). In luminal A subtype, adjunctive radiotherapy could decrease the risk of relapse (P = 0.005), Ki67 positive was a high-risk factor for relapse (P < 0.001), and adjuvant chemotherapies could reduce the relapse for the patients with risk factors (P < 0.001). Adjuvant hormone therapy was an effective treatment for ER-positive tumors (P < 0.001). Molecular subtypes of breast cancer could robustly identify the risk of recurrence and were significant in therapeutic decision making. The model combined subtype and clinical pathology was a significant improvement. Luminal A tumors might represent two distinct subsets which demonstrated distinct prognosis and therapy response.