Minimally Invasive Complete Response Assessment of the Breast After Neoadjuvant Systemic Therapy for Early Breast Cancer (MICRA trial): Interim Analysis of a Multicenter Observational Cohort Study

Ariane A Van Loevezijn,Terry Wiersma,Marieke E.M Van Der Noordaa,Frederieke H Van Duijnhoven,Bas J.G.L Zonneveld,Marie-Jeanne T F D Vrancken Peeters,Charlotte F J M Blanken-Peeters,Gonneke A O Winter-Warnars,Koen K Van De Vijver,Erik D Van Werkhoven,Gabe S Sonke,Emilie J Groen,Claudette E Loo

doi:10.1245/s10434-020-09273-0

Abstract

BackgroundThe added value of surgery in breast cancer patients with pathological complete response (pCR) after neoadjuvant systemic therapy (NST) is uncertain. The accuracy of imaging identifying pCR for omission of surgery, however, is insufficient. We investigated the accuracy of ultrasound-guided biopsies identifying breast pCR (ypT0) after NST in patients with radiological partial (rPR) or complete response (rCR) on MRI.MethodsWe performed a multicenter, prospective single-arm study in three Dutch hospitals. Patients with T1–4(N0 or N +) breast cancer with MRI rPR and enhancement ≤ 2.0 cm or MRI rCR after NST were enrolled. Eight ultrasound-guided 14-G core biopsies were obtained in the operating room before surgery close to the marker placed centrally in the tumor area at diagnosis (no attempt was made to remove the marker), and compared with the surgical specimen of the breast. Primary outcome was the false-negative rate (FNR).ResultsBetween April 2016 and June 2019, 202 patients fulfilled eligibility criteria. Pre-surgical biopsies were obtained in 167 patients, of whom 136 had rCR and 31 had rPR on MRI. Forty-three (26%) tumors were hormone receptor (HR)-positive/HER2-negative, 64 (38%) were HER2-positive, and 60 (36%) were triple-negative. Eighty-nine patients had pCR (53%; 95% CI 45–61) and 78 had residual disease. Biopsies were false-negative in 29 (37%; 95% CI 27–49) of 78 patients. The multivariable associated with false-negative biopsies was rCR (FNR 47%; OR 9.81, 95% CI 1.72–55.89; p = 0.01); a trend was observed for HR-negative tumors (FNR 71% in HER2-positive and 55% in triple-negative tumors; OR 4.55, 95% CI 0.95–21.73; p = 0.058) and smaller pathological lesions (6 mm vs 15 mm; OR 0.93, 95% CI 0.87–1.00; p = 0.051).ConclusionThe MICRA trial showed that ultrasound-guided core biopsies are not accurate enough to identify breast pCR in patients with good response on MRI after NST. Therefore, breast surgery cannot safely be omitted relying on the results of core biopsies in these patients.

Highlights

With systemic treatments becoming increasingly effective, the number of breast cancer patients undergoing breast conserving surgery after neoadjuvant systemic therapy (NST) has increased, and pathological complete response occurs more frequently.[1,2,3] Previous studies have demonstrated that excision of the residual disease, rather than the entire initial tumor bed, does not compromise the recurrence rate in patients undergoing breast conserving treatment after NST.[4,5] It can be questioned as to whether any surgical resection was needed in patients with pCR in the surgical specimen.A major challenge in pursuing a surgery-free treatment strategy for patients with pCR is the identification of pCR without surgery
The multivariable associated with false-negative biopsies was Radiological complete response (rCR) (FNR 47%; OR 9.81, 95% CI 1.72–55.89; p = 0.01); a trend was observed for hormone receptor (HR)-negative tumors (FNR 71% in HER2-positive and 55% in triple-negative tumors; OR 4.55, 95% CI 0.95–21.73; p = 0.058) and smaller pathological lesions (6 mm vs 15 mm; OR 0.93, 95% CI 0.87–1.00; p = 0.051)
Post-NST MRI showed rCR in 136 of 167 (81%, 95% CI 75–87) patients and radiological partial (rPR) in 31 of 167 (19%; 95% CI 13–25) patients

Summary

Introduction

A major challenge in pursuing a surgery-free treatment strategy for patients with pCR is the identification of pCR without surgery Current imaging modalities such as ultrasound, MRI, and18F-FDG PET-CT-scan are not sufficiently accurate to identify pCR.[6,7] Minimally invasive biopsies to detect the presence of residual tumor in the breast after NST have been explored in several pilot studies.[8,9,10,11,12,13,14] The primary outcome of these studies was the false-negative rate (FNR), defined as the proportion of patients with residual disease in the surgical specimen of the breast that had tumor-negative biopsies after NST. We investigated the accuracy of ultrasound-guided biopsies identifying breast pCR (ypT0) after NST in patients with radiological partial (rPR) or complete response (rCR) on MRI.

Methods

Results

Conclusion