Abstract Background: Contrast-enhanced ultrasonography (CEUS) allows a thorough visualization of the intra-tumoral blood flow. This study aimed to determine if CEUS can predict the early effects of neoadjuvant chemotherapy (NAC) on breast cancer. Patients and Methods: We evaluated 93 patients with triple-negative type (ER-negative and HER2-negative, n= 30), HER2-positive (HER2-positive and any ER, n= 34), and luminal type (ER-positive and HER2-negative, n= 29) invasive breast cancer who underwent NAC between September 2012 and March 2019. Ultrasonography (US) and CEUS were performed before NAC and after two cycles of NAC. All patients underwent either mastectomy or breast-conserving surgery after NAC. To objectively evaluate CEUS findings, the ascending slope (AS) in perfusion parameters of CEUS was calculated using time-intensity curves based on enhancement intensity and temporal changes. The changes of maximum tumor diameter in US (ΔUS) and the changes of AS in perfusion parameters of CEUS (ΔAS) were measured in the primary tumor. Results: Thirty-seven (39.8%) patients achieved pathological complete response (pCR). In triple-negative breast cancer, both of ΔUS and ΔAS showed a significant decline with pCR, but there were no significant differences in ΔUS and ΔAS in the luminal-type and HER2-positive breast cancer. We set cutoffs of the ΔUS (-37%, AUC 0.742) and ΔAS (-26%, AUC 0.823) for predicting pCR on the basis of their ROC curves. ΔUS (OR 8.75, p=0.017) and ΔAS (OR 21.3, p=0.0001) in univariate analysis and ΔAS (OR 16.1, p=0.009) in multivariate analysis were significant predictors for pCR in triple-negative breast cancer. The sensitivity, specificity, and accuracy for predicting pCR in triple-negative breast cancer were 0.70, 0.79, and 0.76 in ΔUS and 0.80, 0.84, and 0.83 in ΔAS, respectively. The sensitivity, specificity, and accuracy of ΔAS were greater than those of ΔUS for predicting pCR. Conclusions: CEUS may serve as a new important diagnostic modality when planning therapeutic strategies, for patients with triple-negative breast cancer who received NAC. univariate analysis and multivariate analysis for pCR in triple-negative breast cancerCharacteristicUnivariate logistic analysisMultivariate logistic analysisOR95%CIpOR95%CIpAge, <50 vs ≧500.960.21-4.341.0000Clinical T, T1 vs T2-40.900.13-6.461.0000Clinical N, Negative vs Positive0.360.08-1.720.2635Nuclear Grade, 3 vs 1-20.750.14-3.901.0000Ki67, <20 vs ≧ 20--0.2685US findingsΔUS(%), ≧-37 vs ←378.751.53-50.110.01695.800.73-58.390.1004ΔAS(%), ≧-26 vs ←2621.332.94-154.550.001316.142.28-177.580.0096 Citation Format: Mai Nishina, Norio Masumoto, Akiko Kanou, Kayo Fukui, Yuri Kimura, Ai Amioka, Tomoko Itagaki, Shinsuke Sasada, Akiko Emi, Takayuki Kadoya, Morihito Okada. Contrast-enhanced ultrasonography after two cycles of chemotherapy predicts the outcome of neoadjuvant chemotherapy in triple-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-02-04.