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

Abstract

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.

Keywords: breast cancer; imaging; neoadjuvant systemic therapy (NAST); triple-negative breast cancer (TNBC); ultrasound.

Figure 1.

Imaging schema in patients with triple negative breast cancer according to the ARTEMIS study protocol.

Figure 2.

Images of a 52-year-old woman with triple negative breast cancer in the right breast. (a) Craniocaudal mammogram shows an oval mass (arrow) correlating with the palpable abnormality (triangle). (b, c) Longitudinal and transverse gray-scale ultrasound images of the tumor at baseline evaluation show a hypoechoic mass measuring 2.9 × 2.6 × 1.9 cm. (d, e) Longitudinal and transverse gray-scale ultrasound images of the tumor after 2 cycles of neoadjuvant doxorubicin and cyclophosphamide show the tumor measuring 1.8 × 1.7 × 0.9 cm, with an 80% calculated reduction in tumor volume, suggestive of treatment response predictive of pathologic complete response (pCR). The patient completed neoadjuvant systemic therapy and underwent breast-conserving surgery, and surgical pathology evaluation showed a pCR.

Figure 2.

Images of a 52-year-old woman with triple negative breast cancer in the right breast. (a) Craniocaudal mammogram shows an oval mass (arrow) correlating with the palpable abnormality (triangle). (b, c) Longitudinal and transverse gray-scale ultrasound images of the tumor at baseline evaluation show a hypoechoic mass measuring 2.9 × 2.6 × 1.9 cm. (d, e) Longitudinal and transverse gray-scale ultrasound images of the tumor after 2 cycles of neoadjuvant doxorubicin and cyclophosphamide show the tumor measuring 1.8 × 1.7 × 0.9 cm, with an 80% calculated reduction in tumor volume, suggestive of treatment response predictive of pathologic complete response (pCR). The patient completed neoadjuvant systemic therapy and underwent breast-conserving surgery, and surgical pathology evaluation showed a pCR.

Figure 2.

Images of a 52-year-old woman with triple negative breast cancer in the right breast. (a) Craniocaudal mammogram shows an oval mass (arrow) correlating with the palpable abnormality (triangle). (b, c) Longitudinal and transverse gray-scale ultrasound images of the tumor at baseline evaluation show a hypoechoic mass measuring 2.9 × 2.6 × 1.9 cm. (d, e) Longitudinal and transverse gray-scale ultrasound images of the tumor after 2 cycles of neoadjuvant doxorubicin and cyclophosphamide show the tumor measuring 1.8 × 1.7 × 0.9 cm, with an 80% calculated reduction in tumor volume, suggestive of treatment response predictive of pathologic complete response (pCR). The patient completed neoadjuvant systemic therapy and underwent breast-conserving surgery, and surgical pathology evaluation showed a pCR.

Figure 2.

Images of a 52-year-old woman with triple negative breast cancer in the right breast. (a) Craniocaudal mammogram shows an oval mass (arrow) correlating with the palpable abnormality (triangle). (b, c) Longitudinal and transverse gray-scale ultrasound images of the tumor at baseline evaluation show a hypoechoic mass measuring 2.9 × 2.6 × 1.9 cm. (d, e) Longitudinal and transverse gray-scale ultrasound images of the tumor after 2 cycles of neoadjuvant doxorubicin and cyclophosphamide show the tumor measuring 1.8 × 1.7 × 0.9 cm, with an 80% calculated reduction in tumor volume, suggestive of treatment response predictive of pathologic complete response (pCR). The patient completed neoadjuvant systemic therapy and underwent breast-conserving surgery, and surgical pathology evaluation showed a pCR.

Figure 2.

Images of a 52-year-old woman with triple negative breast cancer in the right breast. (a) Craniocaudal mammogram shows an oval mass (arrow) correlating with the palpable abnormality (triangle). (b, c) Longitudinal and transverse gray-scale ultrasound images of the tumor at baseline evaluation show a hypoechoic mass measuring 2.9 × 2.6 × 1.9 cm. (d, e) Longitudinal and transverse gray-scale ultrasound images of the tumor after 2 cycles of neoadjuvant doxorubicin and cyclophosphamide show the tumor measuring 1.8 × 1.7 × 0.9 cm, with an 80% calculated reduction in tumor volume, suggestive of treatment response predictive of pathologic complete response (pCR). The patient completed neoadjuvant systemic therapy and underwent breast-conserving surgery, and surgical pathology evaluation showed a pCR.

Figure 3.

Positive predictive value (PPV) for pathologic complete response (pCR) by percentage reduction in tumor volume after 2 cycles of neoadjuvant doxorubicin and cyclophosphamide in the discovery cohort (a) and the validation cohort (b). The graph shows a PPV of 77% and 76% for pCR prediction at 80% volume reduction (vertical dotted lines) in the discovery and the validation cohorts, respectively. PPV is shown in red solid line and its 95% exact confident intervals are shown in blue dashed lines.

Figure 3.

Positive predictive value (PPV) for pathologic complete response (pCR) by percentage reduction in tumor volume after 2 cycles of neoadjuvant doxorubicin and cyclophosphamide in the discovery cohort (a) and the validation cohort (b). The graph shows a PPV of 77% and 76% for pCR prediction at 80% volume reduction (vertical dotted lines) in the discovery and the validation cohorts, respectively. PPV is shown in red solid line and its 95% exact confident intervals are shown in blue dashed lines.