Accuracy of Magnetic Resonance Imaging-Guided Biopsy to Verify Breast Cancer Pathologic Complete Response After Neoadjuvant Chemotherapy: A Nonrandomized Controlled Trial

Abstract

Importance: After neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) is an optimal outcome and a surrogate end point for improved disease-free and overall survival. To date, surgical resection remains the only reliable method for diagnosing pCR.

Objective: To evaluate the accuracy of magnetic resonance imaging (MRI)-guided biopsy for diagnosing a pCR after NAC compared with reference-standard surgical resection.

Design, setting, and participants: Single-arm, phase 1, nonrandomized controlled trial in a single tertiary care cancer center from September 26, 2017, to July 29, 2019. The median follow-up was 1.26 years (interquartile range, 0.85-1.59 years). Data analysis was performed in November 2019. Eligible patients had (1) stage IA to IIIC biopsy-proven operable invasive breast cancer; (2) standard-of-care NAC; (3) MRI before and after NAC, with imaging complete response defined as no residual enhancement on post-NAC MRI; and (4) definitive surgery. Patients were excluded if they were younger than 18 years, had a medical reason precluding study participation, or had a prior history of breast cancer.

Interventions: Post-NAC MRI-guided biopsy without the use of intravenous contrast of the tumor bed before definitive surgery.

Main outcomes and measures: The primary end point was the negative predictive value of MRI-guided biopsy, with true-negative defined as negative results of the biopsy (ie, no residual cancer) corresponding to a surgical pCR. Accuracy, sensitivity, positive predictive value, and specificity were also calculated. Two clinical definitions of pCR were independently evaluated: definition 1 was no residual invasive cancer; definition 2, no residual invasive or in situ cancer.

Results: Twenty of 23 patients (87%) had evaluable data (median [interquartile range] age, 51.5 [39.0-57.5] years; 20 women [100%]; 13 White patients [65%]). Of the 20 patients, pre-NAC median tumor size on MRI was 3.0 cm (interquartile range, 2.0-5.0 cm). Nineteen of 20 patients (95%) had invasive ductal carcinoma; 15 of 20 (75%) had stage II cancer; 11 of 20 (55%) had ERBB2 (formerly HER2 or HER2/neu)-positive cancer; and 6 of 20 (30%) had triple-negative cancer. Surgical pathology demonstrated a pCR in 13 of 20 (65%) patients and no pCR in 7 of 20 patients (35%) when pCR definition 1 was used. Results of MRI-guided biopsy had a negative predictive value of 92.8% (95% CI, 66.2%-99.8%), with accuracy of 95% (95% CI, 75.1%-99.9%), sensitivity of 85.8% (95% CI, 42.0%-99.6%), positive predictive value of 100%, and specificity of 100% for pCR definition 1. Only 1 patient had a false-negative MRI-guided biopsy result (surgical pathology showed <0.02 cm of residual invasive cancer).

Conclusions and relevance: This study's results suggest that the accuracy of MRI-guided biopsy to diagnose a post-NAC pCR approaches that of reference-standard surgical resection. MRI-guided biopsy may be a viable alternative to surgical resection for this population after NAC, which supports the need for further investigation.

Trial registration: ClinicalTrials.gov Identifier: NCT03289195.

Figure 1.. Diagram of Participant Flow Through Trial

MRI indicates magnetic resonance imaging.

Figure 2.. Schematic of This Single-Arm, Phase 1, Single-Institution Clinical Trial

Biopsy-proven cancer of the right breast is shown in the pre–neoadjuvant chemotherapy (pre-NAC) image (magenta arrowhead); complete response is shown in the post-NAC image (yellow arrowhead). MRI indicates magnetic resonance imaging.

Figure 3.. Magnetic Resonance Imaging (MRI) Before and After Neoadjuvant Chemotherapy (NAC) Demonstrating an Imaging Complete Response After NAC

A, Axial fat-saturated T1-weighted postcontrast imaging of a biopsy-proven left breast ERBB2 (formerly HER2 or HER2/neu)–positive invasive ductal carcinoma (arrowhead). B, Axial fat-saturated T1-weighted postcontrast imaging of the same patient demonstrating an imaging complete response defined as no residual tumor enhancement in the treated tumor bed as indicated by the accurately positioned biopsy marker (arrowhead) and anatomic landmarks.