RESPONDER – diagnosis of pathological complete response by vacuum-assisted biopsy after neoadjuvant chemotherapy in breast Cancer - a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial

Abstract

BackgroundNeoadjuvant chemotherapy (NACT) is a standard approach of the multidisciplinary treatment of breast cancer. Depending on the biological subtype a pathological complete response in the breast (bpCR) can be achieved in up to 60% of the patients. However, only limited accuracy can be reached when using imaging for prediction of bpCR prior to surgery. Due to this diagnostic uncertainty, surgery after NACT is considered to be obligatory for all patients in order to either completely remove residual disease or to diagnose a bpCR histologically. The purpose of this trial is to evaluate the accuracy of a vacuum-assisted biopsy (VAB) to diagnose a bpCR after NACT prior to surgery.MethodsThis study is a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial. The study will take place at 21 trial sites in Germany. Six hundred female patients with breast cancer after completed NACT showing at least a partial response to NACT treatment will be enrolled. A vacuum-assisted biopsy (VAB) guided either by ultrasound or mammography will be performed followed by histopathological evaluation of the VAB specimen before standard, guideline-adherent breast surgery. The study is designed to prove that the false negative rate of the VAB is below 10%.DiscussionAs a bpCR is becoming a more frequent result after NACT, the question arises whether breast surgery is therapeutically necessary in such cases. To study this subject further, it will be crucial to develop a reliable test to diagnose a bpCR without surgery.During the study we anticipate possible problems in patient recruitment as the VAB intervention does not provide participating patients with any personal benefit. Hence, a proficient informed consent discussion with the patient and a detailed explanation of the study aim will be crucial for patient recruitment. Another critical issue is the histopathological VAB evaluation of a non-tumorous specimen as this may have been taken either from the former tumor region (bpCR) or outside of the (former) tumor region (non-representative VAB, sampling error).Trial registrationThe trial has been registered at clinicaltrials.gov with the identifier NCT02948764 on October 28, 2016 and at the German Clinical Trials Register (DRKS00011761) on February 20, 2017. The date of enrolment of the first participant to the trial was on March 8, 2017.

The ongoing evaluation and evolution of breast cancer surgical care

“…The pathology results will be recorded as residual tumor, no residual tumor, or no residual tumor but the biopsy is not representative of prior tumor. The pathology results from both the biopsy and the surgical specimen will be compared, with the goal of the study to prove a false‐negative rate ˃10% . These studies may provide the stepwise data that can demonstrate that surgical resection can be eliminated when followed by radiotherapy in appropriate responders.…”

“…The pathology results from both the biopsy and the surgical specimen will be compared, with the goal of the study to prove a false-negative rate ˃10%. 14,15 These studies [13][14][15] may provide the stepwise data that can demonstrate that surgical resection can be eliminated when followed by radiotherapy in appropriate responders.…”

Towards de-escalation of axillary management after neoadjuvant chemotherapy in breast cancer

“…28 Such a protocol results in a decrease in ALND 29 , but it is yet unknown whether omission of ALND after chemotherapy in cN+ patients will impact long-term prognosis. In 2016, results of the Targeted Axillary Dissection (TAD) were published 30 , in which both the pathologically proven positive lymph node (marked prior to chemotherapy) and the SLNs are removed. The marked node was not an SLN in 23% of patients and an excellent FNR (2%) and NPV (97%) were reported for TAD.…”

“…However, this single-center study consisted of a small cohort and patients were retrospectively identified from a prospective registry. 30 The Dutch multicenter RISAS trial was set up in 2015 (funded by KWF Kankerbestrijding) to validate the combination of MARI and SLND in 225 cN+ patients. The RISAS study protocol is presented in this thesis.…”

“…Another validation trial is ongoing in Germany; the RESPONDER trial. 30 It is planned to enroll 600 patients (all subtypes included) with a partial or complete response on imaging that will undergo at least 12 image-guided vacuum assisted biopsies of the breast, subsequently followed by breast conserving surgery or mastectomy. The primary endpoint of the trial is the false negative rate of the biopsies.…”