The value of HIF-1, TWIST-1, ITGB-1, and Ki-67, and a possible new combined index (predRCB) for predicting NACT responses was assessed by receiver operating characteristic (ROC) curves. Results HIF-1, TWIST-1, and ITGB-1 expression were positively correlated with tumor stiffness and negatively with OS. OS. Area under the ROC curves (AUCs) measuring the overall performance of HIF-1, TWIST-1, ITGB-1, and Ki-67 for predicting responses to NACT were 0.81, 0.85, ELN484228 0.79, and 0.80 for favorable responses, and 0.83, 0.86, 0.84, and 0.85 for resistant responses, respectively. PredRCB showed better prediction than the other individual indexes for favorable responses (AUC = 0.88) and resistant responses (AUC = 0.92). Conclusion HIF-1, TWIST-1, ITGB-1, and Ki-67 performed well in predicting favorable responses and resistance to NACT, and predRCB improved the predictive power of the individual indexes. These results support individualized treatment of BC patients receiving NACT. analysis was utilized for pairwise comparisons among three groups if the results of the KruskalCWallis test or ANOVA test were significant. analysis was also performed for pairwise comparisons among three groups if the results of the 2 2 test were significant. Inter-observer reproducibility of Ki-67, HIF-1, TWIST-1, and ITGB-1 was assessed by computing intra-class correlation coefficients (ICC). The detail parameters were as follows: Model: Two-Way ELN484228 Mixed-Effect model; Type: single measure; Definition: absolute agreement.28 Pearsons correlation (rp) and Spearmanscorrelation (rs) analyses were used to analyze the associations among SWE stiffness, OS, HIF-1, TWIST-1, and ITGB-1 expression. The area under the ROC curve (AUC) values were used to determine the predictive diagnostic overall performance of HIF-1, TWIST-1, ITGB-1, and Ki-67. A new predictive biomarker (predRCB) was combined with the largest AUC of new predictors (HIF-1, TWIST-1, and ITGB-1) and the traditional one (Ki-67) according to the results of the multivariable linear regression model. Differences were considered significant when the two-sided value was 0.05. Results Baseline Characteristics of Patients in the Three Groups The baseline characteristics are summarized in Table 1. Among the 104 patients who underwent breast and axillary surgery 3C4 weeks after NACT, 23 (22%) showed a favorable response (PCR and RCB-I), 48 (46.2%) showed a moderate response (RCB-II), and 33 (31.7%) showed NACT resistance (RCB-III). In the subpopulations according to molecular subtype, the rate of PCR+RCB-I was 21.7% in the triple negative type, 26.1% in the HER2-positive type, 17.4% in the luminal A type, and 39.1% in the luminal B type. The RCB-III rate was 0% in the triple unfavorable type, 4.2% in the HER2-positive type, 21.2% in the luminal A type, and 72.7% in the luminal B type. There were significant differences among the three RCB groups ( 0.05) for most clinical indicators, except for HER2 positivity in Immunohistochemical marker, T2 in Tumor size, Grade 2 and Grade 3 in Grade, and IIIB in Clinical stage. The imaging indicators Emax, Emean, and OS were also significantly different among the three groups ( 0.05). Figures 1 and ?and22 show the SWE and DOBI images of one lesion 1 day before NACT, respectively. Table 1 Baseline Characteristics of Patients value 0.01). Specifically, patients in the resistance group showed higher HIF-1, TWIST-1, and ITGB-1 expression and lower Ki-67 expression, whereas those in the favorable response group showed lower HIF-1, TWIST-1, and ITGB-1 expression and higher Ki-67 expression. Table 2 HIF-1, TWIST1, ITGB1, and Ki-67 Expression in the Three RCB Groups value= C0.812, 0.001) and Emean and OS = C0.715, 0.001); positive correlations were observed between HIF-1 and TWIST-1 expression = 0.797, 0.001), between HIF-1 and ITGB-1 expression (rp = 0.852, 0.001), and between TWIST-1 and ITGB-1 expression = 0.814, 0.001); unfavorable correlations were observed between Ki-67 and HIF-1 expression (rp = C0.404, 0.001), between Ki-67 and TWIST-1 expression = C0.467, 0.001), and between Ki-67 and ITGB-1 expression (rp = ?0.358, 0.001). The correlations of immunohistochemical features with SWE stiffness and OS at baseline are shown in Table 3. The results showed that HIF-1, TWIST-1, and ITGB-1 expression levels were positively correlated with SWE stiffness (Emean and Emax) and negatively correlated with OS. In addition, Ki-67 showed no or poor correlation with SWE stiffness and OS at baseline. Table 3 Associations Between HIF-1, TWIST-1, ITGB-1, and Ki-67 Expression ELN484228 and SWE Stiffness and OS valuevaluevaluevalue /th /thead Molecular subtype?Luminal A1.000.0001.00C1.000.0050.930.070.79C1.000.01?Luminal B0.900.0440.81C0.98 0.0010.910.040.83C0.99 0.001?Triple unfavorable0.890.1010.69C1.000.010CCCC?HER20.950.050.85C1.000.0030.780.170.44C1.000.20Pathological types?Invasive ductal carcinoma0.860.040.78C0.94 0.0010.920.030.86C0.97 0.001?Invasive lobular carcinoma1.000.001.00C1.000.0140.950.070.81C1.000.03?Grade?Grade 20.880.040.81C0.95 0.0010.900.030.84C0.97 0.001?Grade size (cT)?T10.570.200.19C0.960.770CCCC?T20.840.050.75C0.94 0.0010.880.040.80C0.96 0.001?T31.000.001.00C1.00 0.0010.960.030.90C1.00 0.001NTake action regimens:?TEC0.930.030.86C1.00 IgM Isotype Control antibody (APC) 0.0010.920.030.85C0.98 0.001?TE0.640.180.30C0.990.4501.000.001.00C1.000.114?FECCCCC0.790.150.48C1.000.242?TH0.750.110.54C0.960.2611.000.001.00C1.000.008 Open in a separate window Note: C: Unable to calculate due to small sample size after subgrouping. Abbreviations: NACT, neoadjuvant chemotherapy; TEC, (docetaxel, epirubicin, and cyclophosphamide); TE (docetaxel and epirubicin); FEC (5-fluorouracil, epirubicin, and cyclophosphamide); TH (docetaxel and herceptin); AUC, area under the receiver operating.