ObjectiveTo investigate the relation between mammographic density (MD) and the efficacy of neoadjuvant chemotherapy (NACT) for patients with breast cancer. MethodsThe clinicopathologic data of patients diagnosed with breast cancer in the Affiliated Hospital of Southwest Medical University from January 2019 to December 2021 and met the inclusion and exclusion criteria of this study were collected. According to the 5th edition of the Breast Imaging-Reporting and Data System, the MD was classified into 4 categories: a, b, c, and d. Based on the pathological evaluation systems of Miller-Payne and Residual Cancer Burden, the new and improved pathological criteria was structured including the residual cancer cell and lymph node statuses to evaluate the pathological changes of breast cancer after NACT. After adjusting the factors affecting MD, the original model (only including MD categories as independent variables), the minimum adjustment model (adding age, body mass index, and menopausal status as independent variables), and the fully adjusted model (further including estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, axillary lymph node status at the initial diagnosis, and NACT regimen) were used to analyze the relation between MD and NACT effect. In the 3 models, the MD category a was used as the reference. ResultsA total of 287 patients with breast cancer were enrolled in this study. Thirty-eight, 76, 114, and 59 of whom with MD category a, b, c, and d respectively, and 14, 74, 117, and 82 of whom with grade L1, L2, L3, and L4 of NACT effect respectively. No matter in integrated patients or premenopausal patients, the results of the fully adjusted model showed that, the regression coefficient of MD classification was negative, and with the increase of MD classification, the odds ratio was <1 and showed a decreasing trend. ConclusionsFrom the results of this study, the increase of MD classification may have a negative impact on the effect of NACT. Namely, effect of NACT is poor in integrated patients or premenopausal patients of whom with higher MD. MD can be used as a predictor of NACT effect, so as to guide doctors in the selection and individual management of neoadjuvant therapy, and improve the prognosis of patients with breast cancer.