ObjectiveTo provide reference for further treatment by analyzing the relationship between mutant genes of breast cancer and histological classification and molecular typing of breast cancer.MethodsRetrospectively collectted the pathological specimens of 46 breast cancer patients who treated by the Dongguan Maternal and Child Health Hospital and the Dongguan Houjie Hospital between February 2016 and August 2017 without chemotherapy. Among the selected 46 breast cancer patients, we detected tumor tissue estrogen receptor (ER)/ pregnancy hormone receptor (PR)/human epidermal growth factor receptor-2 (HER-2) status by immunohistochemistry and classified the pathological tissue section. By using multiple PCR techniques, we detected 207 hot mutation regions of the 50 extended tumor-related genes on the semiconductor sequencing platform.ResultsThere were 8 cases of grade Ⅰ, 18 cases of grade Ⅱ, 20 cases of grade Ⅲ in 46 breast cancer patients according to histological grade. Of the 46 cases, there were 23 cases of Luminal B, 9 cases of Luminal A, 9 cases of HER-2 (+), 5 cases of type besal-like according to ER/PR/HER-2 expression status. Moreover, we found that there were 33 gene locus mutations of 8 genes, including AKT1, APC, BRAF, CDKN2A, KRAS, PTEN, PIK3CA, and TP53. Among of them, the mutation of PIK3CA gene took the most of 24 cases, followed by TP53 (18 cases), 2 cases of CDKN2A gene mutation, and 1 case in the remaining four types of genes respectively. we found that the gene mutations of breast cancer were not related to the histological classification and molecular type (P>0.05), the PIK3CA gene mutation was related to the histological classification of breast cancer, the lower the histological classification level, the higher PIK3CA gene mutation rate (P<0.05). TP53 gene mutation was not related to histological grading and molecular type (P>0.05).Conclusions The PIK3CA gene mutation rate in patients with histological grading Ⅰ level increased significantly. The combination of PIK3CA gene mutation and histological grading of breast cancer may become a molecular biological indicator to judge the degree of malignancy and prognosis of breast cancer.