Multiparametric contrast-enhanced ultrasound in early prediction of response to neoadjuvant chemotherapy and recurrence-free survival in breast cancer

Abstract Background Contrast-enhanced ultrasound (CEUS) is a promising tool and can facilitate dynamic observation and quantification of tumor perfusion without exposing the patients to any risk of radiation. This preliminary study aimed to investigate the value of CEUS in early predicting pCR and RFS in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC). Methods In this retrospective interpretation of prospective data study, consecutive women with LABC who underwent CEUS examination pre-NAC and after one or two cycles of NAC from March 2014 to October 2018 were included. Written informed consent was obtained from all patients. CEUS qualitative parameters before NAC and quantitative parameters (peak intensity, PEAK; time to peak, TTP; regional blood volume, RBV; regional blood flow, RBF, and mean transit time, MTT) during NAC and their changes were assessed. The relative changes in CEUS parameters and tumor diameter after one and two cycles of NAC were describe as ΔA 1 and ΔA 2 , respectively. Multivariate logistic regression analysis was performed to identify independent variables associated with pCR. Cox proportional hazards model and Kaplan-Meier analysis were used to investigate the independent variables of CEUS and clinical-pathologic factors with RFS. Results Among 122 patients (mean age, 51years), 44 (36.1%) underwent PCR. Logistic regression analysis showed that molecular subtype, PEAK 1 and △ diameter 1 were the best predictors of pCR after one cycle of NAC (area under the receiver operating characteristic curve [AUC], 0.81; 95%CI: 0.73, 0.88); Molecular subtype, PEAK 2 and △ TTP 2 were independently associated with pCR after two cycles of NAC (AUC, 0.85, 95% CI: 0.77, 0.91). After 63 months of median follow-up, there were 17 recurrences. Multivariable Cox proportional hazards analysis revealed that a higher clinical T (hazard ratio [HR] = 4.75; 95% CI: 1.75, 12.87; P = 0.002) and N stages (HR = 3.39; 95% CI: 1.25, 9.19; P = 0.02), and a longer TTP (HR = 1.06; 95% CI: 1.01,1.11; P = 0.02) at pre-NAC CEUS were independently associated with poorer RFS. Conclusions CEUS can be used as a noninvasively functional technique to early predict pCR as well as RFS in breast cancer patients treated with NAC.