Accuracy of ultrasound for predicting pathologic response during neoadjuvant therapy for breast cancer

Abstract

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 5 0.01). For WHO-2D, DORs were as follows: 4.07 (ypT0,ypN0), 3.75 (ypT0/is,ypN0), 3.14 (ypT0/ is,ypN1/2) and 2.65 (ypT0/is/1a,ypN1/2). DORs did not differ between US criteria (p 5 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 5 81.7%, specificity 5 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.Neoadjuvant chemotherapy (NAC) has a well-established role in the management of breast cancer, with randomised controlled trials showing similar long-term disease-free survival (DFS) and overall survival (OS), and increased rates of breast conserving surgery compared with upfront surgery and adjuvant therapy. 1 A key advantage of NAC is the opportunity to assess response early during treatment as a predictor of pathologic complete response (pCR) at the end of therapy 2 (a surrogate marker for prolonged DFS and OS), and for treatment modification to increase DFS and OS in hormone receptor positive breast cancers. 3 Randomised controlled trials that assessed early response by clinical examination and ultrasound (US) have indicated benefits of therapy modification in responders and non-responders. Increased rates of pCR, breast conservation and improved OS were found in the Aberdeen trial for responders randomised to taxanes after four cycles of anthracycline-based NAC relative to those continuing treatment. 4,5 The GeparTrio trial randomised early responders to standard or extended anthracycline/taxanebased NAC and found longer DFS and a trend towards longer OS when therapy was extended. 6 Improved DFS and treatment ...

Monitoring Neoadjuvant Chemotherapy for Breast Cancer by Using Three-dimensional Subharmonic Aided Pressure Estimation and Imaging with US Contrast Agents: Preliminary Experience

“…Many studies have investigated monitoring of neoadjuvant therapeutic response, and pathologic response assessment has been widely used as an end point reference (3,4,(6)(7)(8)(9)(10). However, the definition of pathologic complete response varies among studies, and the prognostic value of pathologic complete response depends on breast cancer type (6,8,29).…”

“…However, the optimal method for monitoring the response to neoadjuvant therapy has not been established (6). Ultrasonography (US), magnetic resonance (MR) imaging, and positron emission tomography (PET)/ computed tomography (CT) have been investigated as monitoring tools but are not standardized (7)(8)(9). Currently, clinical breast examination, mammography, US, and, in selected patients, MR imaging are used at diagnosis, during chemotherapy, and after completion of (24).…”

Magnetic Resonance Imaging after Completion of Neoadjuvant Chemotherapy Can Accurately Discriminate between No Residual Carcinoma and Residual Ductal Carcinoma In Situ in Patients with Triple-Negative Breast Cancer

“…Recently, Lee et al [ 22 ] summarized inaccuracies among current practical tools used to evaluate residual tumor volumes in response to NCT and demonstrated that two-dimensional and three-dimensional ultrasound and breast MRI show similar performances for the estimation of residual breast cancer volume and prediction of pCR. In a retrospective analysis of patients enrolled in the GeparTrio trial, ultrasound showed a high sensitivity for predicting ypT0 and ypN0 and modestly improved the prediction of pCR by patient characteristics, which was concluded to be a potentially useful modality for early prediction of pCR, despite breast MRI not being included in the study [ 23 ]. In addition, ultrasound provides clinical advantages over MRI including lower complexity, easier accessibility, shorter procedure time, easier interpretation, cheaper costs, and lack of the hazards associated with contrast agents [ 22 , 23 ].…”

Early Assessment Window for Predicting Breast Cancer Neoadjuvant Therapy Using Biomarkers, Ultrasound, and Diffuse Optical Tomography

“…Similar results were obtained (details in Appendix A). However, because of its low cost and accessibility, US has been utilized and evaluated in several studies (9)(10)(11)(12). In the GepharTrio trial of 2090 patients bidimensional US measurements at EOC2 were used to classify response and randomize patients to treatment with 6 vs 8 cycles of NAC (11).…”