Abstract OT2-01-04: Towards omitting breast cancer surgery in patients with pathologic complete response after neoadjuvant systemic therapy: The MICRA trial (minimally invasive complete response assessment)
Authors: van der Noordaa ME , van Duijnhoven FH , Loo CE , van Loevezijn A , van Werkhoven E , van de Vijver KK , Wiersma T , Winter-Warnars HA , Sonke GS , Vrancken Peeters M-JT 
Published: May 2019

Background

Improvements in neoadjuvant systemic therapy (NST) for breast cancer patients have led to increasing rates of pathologic complete response (pCR). Breast-conserving surgery (BCS) after NST is considered safe, despite the fact that the original tumor bed is not entirely excised. It can therefore be hypothesized that breast surgery could be omitted in patients achieving pCR. However, since imaging modalities are insufficiently accurate to predict pCR after NST, the need for surgery is unchanged. The MICRA trial is designed to determine the value of ultrasound guided biopsy of the breast in identifying pCR after NST. The ultimate aim of our study is to eliminate surgery of the breast in patients achieving pCR, consequently improving quality of life of these patients.

Trial design

The MICRA trial is a multi-center observational prospective cohort study. Inclusion and exclusion criteria are presented in table 1. In all patients receiving NST, a marker is placed in the center of the tumor area pre-NST. Magnetic resonance imaging (MRI) is performed pre-NST and just before or after the last course of NST. Patients with radiologic complete response (rCR; complete absence of pathologic contrast enhancement) or partial response (rPR, 0.1-2.0 cm residual contrast enhancement, ≥30% decrease in tumour size) are eligible for participation. In these patients, 8 ultrasound guided biopsies are obtained in the region surrounding the marker: 4 central (&lt;0.5 cm) and 4 peripheral biopsies (0.5-1.5cm). Hereafter, conventional surgery is performed (BCS or mastectomy) and pathology results of the biopsies and resected specimen are compared. Pathology findings are scored using Miller-Payne criteria. To evaluate the quality and representativeness of the biopsies, biopsies are categorized according to length and pathology results.

Statistical analysis and accrual

The primary endpoint of the trial is the false-negative rate (FNR) of the biopsy procedure. If the true FNR is 3%, 130 patients without pCR in specimen are sufficient to show that the FNR does not exceed 8% using a one-sided binomial test with a significance α-level of 0.05. With an expected average pCR rate of 65%, 375 patients with rCR will be included. In the rPR-group the expected pCR rate is 12% and therefore 150 patients will be included. In total 525 patients will be included. Until now, 144 patients have been included.

Conclusion

The ultimate aim of the MICRA trial is to eliminate surgery of the breast in patients achieving pCR, by identifying pCR with use of ultrasound guided biopsy. In this scenario, local therapy in patients with pCR would be restricted to radiotherapy.

Table 1:Inclusion and exclusion criteriaInclusion criteriaExclusion criteriaWomen with invasive breast cancer &gt;18 years (all histological subtypes and tumor subtypes)DCIS as shown by core biopsy prior to NSTTumor histology and receptor status established by pre-NST biopsyWomen with distant metastatic diseaseComplete or partial response on post-NST MRIHistory of ipsilateral breast cancerMarker placed in tumor prior to NST Correct position of marker confirmed by mammography or ultrasound 

Citation Format: van der Noordaa ME, van Duijnhoven FH, Loo CE, van Loevezijn A, van Werkhoven E, van de Vijver KK, Wiersma T, Winter-Warnars HA, Sonke GS, Vrancken Peeters M-JT. Towards omitting breast cancer surgery in patients with pathologic complete response after neoadjuvant systemic therapy: The MICRA trial (minimally invasive complete response assessment) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-01-04.