Objective To assess the levels of peripheral blood markers including carbohydrate antigen 15-3 （CA15-3）， carbohydrate antigen 125 （CA125）， carcinoembryonic antigen （CEA）， cytokeratin-18 （CK18）， and neutrophil-to-lymphocyte count ratio （NLR） in breast cancer patients， investigate their correlation with clinicopathological characteristics， and evaluate the impact of neoadjuvant chemotherapy. Methods The clinical data of 187 patients with breast cancer who underwent neoadjuvant chemotherapy at our hospital between January 2020 and December 2023 were retrospectively analyzed. Based on the evaluation criteria for solid tumor response after 8 cycles of chemotherapy， the patients were divided into two groups： an effective group （n = 84） and an ineffective group （n = 103）. The levels of CA15-3， CA125， CEA， CK18， and NLR in the peripheral blood of breast cancer patients before neoadjuvant chemotherapy were measured. Furthermore， a comparison was made between the levels of CA15-3， CA125， CEA， CK18， and NLR in the peripheral blood among breast cancer patients with different clinicopathological characteristics. Additionally， a comparison was conducted between the levels of CA15-3， CA125， CEA， CK18，and NLR in the peripheral blood as well as clinical data between the effective group and ineffective group. Univariate and multivariate logistic regression analyses were employed to examine the factors influencing the ineffectiveness of neoadjuvant chemotherapy in breast cancer patients. Additionally， a receiver operating characteristic （ROC） curve was constructed to assess the predictive efficacy of peripheral blood markers including CA15-3， CA125， CEA， CK18， and NLR on the response to neoadjuvant chemotherapy in breast cancer patients. Results The levels of CA15-3， CA125， CEA， CK18， and NLR in the peripheral blood of breast cancer patients with T₃~T₄ stage， N₁~N₃ stage， and human epidermal growth factor receptor-2 （HER-2） positivity were significantly elevated compared to those in breast cancer patients with T₂ stage， N₀ stage， and HER-2 negativity （P < 0.05）. The levels of CA15-3， CA125， CEA， CK18， and NLR in the peripheral blood were found to be higher in the ineffective group than in the effective group （P < 0.05）. Moreover， a higher proportion of patients in the ineffective group exhibited T₃~T₄ stage tumors along with N₁~N₃ lymph node involvement. Additionally observed were histological grade of low differentiation as well as positive progesterone receptor and estrogen receptor expression. Furthermore high expression of tumor proliferation antigen was more prevalent among patients classified under the ineffective group. （P < 0.05）. Elevated peripheral blood CA15-3， CA125， CEA， CK18 and NLR levels， T₃~T₄ stage， N₁~N₃ stage， low differentiation， and ER positive were identified as significant risk factors for neoadjuvant chemotherapy in breast cancer patients （P < 0.05）. The predictive performance of peripheral blood CA15-3， CA125， CEA， CK18 and NLR in assessing the efficacy of neoadjuvant chemotherapy yielded a sensitivity of 96.43%， specificity of 82.52%， and an area under the curve （AUC） value of 0.956. Furthermore， combined prediction demonstrated higher sensitivity and AUC compared to individual predictors （P < 0.05）， while maintaining similar specificity levels. Conclusions The levels of CA15-3， CA125， CEA， CK18 and NLR in peripheral blood are closely associated with the clinicopathological characteristics of breast cancer patients and can impact the efficacy of neoadjuvant chemotherapy. These biomarkers have potential for predicting response to neoadjuvant chemotherapy in breast cancer patients， with improved accuracy when used in combination.