Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer allows therapy to be tailored; however, optimal response assessment methods have not been established. We estimated the accuracy of ultrasound (US) to predict pathologic complete response (pCR) using common response criteria and pCR definitions, and estimated incremental accuracy over known prognostic variables. Participants undergoing US after two cycles in the GeparTrio trial randomised to no change in NAC were eligible. US response by World Health Organisation (WHO) criteria (1D or 2D) and Response Evaluation Criteria In Solid Tumours (RECIST) was assessed. Four pCR definitions were applied. Sensitivity (correct prediction of pCR), specificity (correct prediction of no-pCR) and diagnostic odds ratios (DORs) were calculated. Areas under the curve (AUCs) were derived from logistic regression including patient variables with and without US. In 832 patients, DORs decreased as pCR definitions became less stringent (p= 0.01). For WHO-2D, DORs were as follows: 4.07 (ypT0,ypN0), 3.75 (ypT0/is,ypN0), 3.14 (ypT0/is,ypN+/−) and 2.65 (ypT0/is/1a,ypN+/−). DORs did not differ between US criteria (p= 0.60). High sensitivity and lower specificity were found for WHO-2D and RECIST; WHO-1D was highly specific with low sensitivity. Sensitivity was highest for WHO-2D predicting ypT0,ypN0 (sensitivity = 81.7%, specificity = 47.6%vs. 42.3% and 80.4% for WHO-1D). Adding US to models including patient variables (age, T-stage, histology and subtype) improved AUCs for predicting pCR by 2–3%. In conclusion, US accuracy is highest for predicting ypT0,ypN0, shown to be most prognostic of long-term survival. WHO-2D and RECIST maximise sensitivity; WHO-1D maximises specificity. US modestly improves the prediction of pCR by patient characteristics.What's new?
Ultrasound is commonly used to assess “early” responses to neoadjuvant chemotherapy, which is given before primary treatment of breast cancer to shrink the tumor. However, its remains unclear whether ultrasound can accurately predict the absence of all residual invasive cancer in the breast tissue (pathological complete response). The authors performed an extensive study using Response Evaluation Criteria in Solid Tumors and World Health Organization criteria for response. Accuracy was higher than previously reported, indicating that the role of ultrasound is currently underestimated in response assessment guidelines.