Early ultrasound evaluation identifies excellent responders to neoadjuvant systemic therapy among patients with triple‐negative breast cancer

• Published in: Cancer 2021-08, Vol.127 (16), p.2880-2887
• Main Authors: Adrada, Beatriz E., Candelaria, Rosalind, Moulder, Stacy, Thompson, Alastair, Wei, Peng, Whitman, Gary J., Valero, Vicente, Litton, Jennifer K., Santiago, Lumarie, Scoggins, Marion E., Moseley, Tanya W., White, Jason B., Ravenberg, Elizabeth E., Yang, Wei T., Rauch, Gaiane M.
• Format: Article
• Language: English
• Subjects: Anthracycline; Anthracyclines - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers; Breast cancer; Confidence intervals; Female; Heterogeneity; Humans; imaging; Medical imaging; neoadjuvant systemic therapy (NAST); Neoadjuvant Therapy - methods; Oncology; Patients; Performance evaluation; Regression analysis; Statistical analysis; Taxanes; Taxoids - therapeutic use; Therapy; Treatment Outcome; Triple Negative Breast Neoplasms - diagnostic imaging; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; triple‐negative breast cancer (TNBC); Tumor Burden; Ultrasonic imaging; Ultrasonography; Ultrasound
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.33604

BACKGROUND Heterogeneity exists in the response of triple‐negative breast cancer (TNBC) to standard anthracycline (AC)/taxane‐based neoadjuvant systemic therapy (NAST), with 40% to 50% of patients having a pathologic complete response (pCR) to therapy. Early assessment of the imaging response during NAST may identify a subset of TNBCs that are likely to have a pCR upon completion of treatment. The authors aimed to evaluate the performance of early ultrasound (US) after 2 cycles of neoadjuvant NAST in identifying excellent responders to NAST among patients with TNBC. METHODS Two hundred fifteen patients with TNBC were enrolled in the ongoing ARTEMIS (A Robust TNBC Evaluation Framework to Improve Survival) clinical trial. The patients were divided into a discovery cohort (n = 107) and a validation cohort (n = 108). A receiver operating characteristic analysis with 95% confidence intervals (CIs) and a multivariate logistic regression analysis were performed to model the probability of a pCR on the basis of the tumor volume reduction (TVR) percentage by US from the baseline to after 2 cycles of AC. RESULTS Overall, 39.3% of the patients (42 of 107) achieved a pCR. A positive predictive value (PPV) analysis identified a cutoff point of 80% TVR after 2 cycles; the pCR rate was 77% (17 of 22) in patients with a TVR ≥ 80%, and the area under the curve (AUC) was 0.84 (95% CI, 0.77‐0.92; P < .0001). In the validation cohort, the pCR rate was 44%. The PPV for pCR with a TVR ≥ 80% after 2 cycles was 76% (95% CI, 55%‐91%), and the AUC was 0.79 (95% CI, 0.70‐0.87; P < .0001). CONCLUSIONS The TVR percentage by US evaluation after 2 cycles of NAST may be a cost‐effective early imaging biomarker for a pCR to AC/taxane‐based NAST. Early ultrasound imaging identifies excellent responders to neoadjuvant systemic therapy among patients with triple‐negative breast cancer. The percentage of tumor volume reduction by ultrasound may be a cost‐effective imaging biomarker for predicting a pathologic complete response.