Diagnosis of Pathological Complete Response by Vacuum-assisted Biopsy After Neoadjuvant Chemotherapy in Breast Cancer

Study Overview
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Brief Summary
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The main purpose of the study is to evaluate the potential of a minimal invasive, vacuum-assisted biopsy (VAB) to reliably diagnose a pathological complete response (pCR) in the breast after neoadjuvant chemotherapy (NACT) in breast cancer patients. The study is designed as a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial, in which we aim to confirm the applicability of preoperative VAB in patients after NACT. Furthermore, we aspire to quantify the rate of concordant pathological findings (pCR yes / no) in biopsy and surgical specimen.

Detailed Description
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In clinical routine surgical treatment follows the pre-operative chemotherapy (NACT). However, recent studies have demonstrated that shrinking tumors need less surgical treatment indicating that patients with pCR could potentially be spared of surgery in the future. However, up to now, prediction of pCR after NACT is only moderately accurate. This prospective, monocenter diagnostic trial aims to explore if minimal invasive biopsies (MIB) might overcome this diagnostic challenge. Ultrasound guided VAB will be performed on 600 breast cancer patients after NACT and directly prior to surgery. There are only two trial visits that are specific to the trial. All other visits will be routine visits. The first trial visit will take place in order to provide the patient with detailed information on the study, its' aims, the VAB procedure, and its risks. The patient will be asked to sign a form of informed consent. At the second trial visit the performance of the VAB (=index test) will take place. This trial visit may vary by patient, tumor, and trial site characteristics and may either be: An ultrasound guided VAB or A stereotactically / mammographically guided VAB. All possible VAB procedures and settings (in outpatient clinic, or in operating room directly before the surgery) are equally accepted. We will allow every trial site to choose the adequate setting to the trial site´s and to their patients' needs. A visit for a follow up will not be necessary in this setting. Possible complications of the VAB procedure may occur while the biopsy is taken. The pathological results of the VAB specimen will be generally categorized as follows: Residual tumor cells in VAB specimen (=non-pCR) No residual tumor cells in the VAB specimen and VAB representative of former tumor region (=pCR in VAB) No residual tumor cells in the VAB specimen but VAB unclear or not representative of former tumor region (=possible sampling error). These VABs are categorized as uninformative for the primary endpoint of the clinical trial. The results will be compared to those of the pathological examination of surgical specimen.

Official Title
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RESPONDER Trial - Diagnosis of Pathological Complete Response by Vacuum-assisted Biopsy After Neoadjuvant Chemotherapy in Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Device: Vacuum-Assisted Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Female patients with primary breast cancer after Neoadjuvant Chemotherapy (NACT) treatment which has been performed for at least 12 weeks and resulted in cPR or cCR (see below). >/=18 years any cT and cN stage, except cT4 stages any routine breast cancer surgical intervention planned according to guidelines (breast conservation or mastectomy) Residual intramammary target lesion or clip marker is visible in ultrasound and / or mammography Diagnosis of imaging complete or partial response according to RECIST 1.1 by at least mammography or ultrasound, according to local routine) Inclusion of only one breast per patient, in bilateral cancer one breast can be included In case of multicentric disease: confirmation of the same tumorbiological subtype defined by immunohistology in at least 2 lesions. Ability of subject to understand character and individual consequences of the clinical trial. Written informed consent (must be available before enrolment in the trial). Exclusion Criteria Palliative or recurrent breast cancer in case of clip marker = target lesion: dislocation of marker (>5mm distance to the initial lesion border at the time of clip placement) contraindication for VAB or associated procedures (e.g. local anesthesia) Pregnancy and lactation held in an institution by legal or official order legally incapacitated.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: single-arm study<br>This project is designed as a one-armed diagnostic study. Every patient included in the study will undergo the same diagnostic test, the vacuum-assisted biopsy, after NACT and before surgery according to guidelines. | Device: Vacuum-Assisted Biopsy<br>* The vacuum-assisted (7-10G), minimal invasive biopsy (VAB), either guided by ultrasound, or by mammography (stereotaxy) during the second trial visit (V2) will be performed once. In analogy to the German S3 guideline on primary breast cancer management we recommend to take at least 12 biopsies with 10G needles or less in case of larger needle sizes.<br>* Other names: minimal invasive biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| false negative VAB results, reported as the false negative rate (= FNR) | non-detected residual tumor by VAB (=index test) compared to breast surgery (=reference test): FNR = rate of patients with non-detected residual tumor by VAB compared to breast surgery Residual tumor is defined as a positive result; in surgical specimen as well as in VAB. | after breast surgery, up to 6 weeks after VAB | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| negative predictive value (NPV) | The negative predictive value (NPV) will be calculated as the quotient of the number of cases with pCR in VAB and in surgical specimen (= true negative result), divided by the total number of cases with pCR in VAB. Residual tumor is defined as a positive result; in surgical specimen as well as in VAB. | after breast surgery, up to 6 weeks after VAB | 
| positive predictive value (PPV) | The positive predictive value (PPV) will be calculated as the number of biopsies with detected residual tumor cells in VAB and surgery (= true positive results) divided by the number of all cases with residual tumor cells in the VAB. Residual tumor is defined as a positive result; in surgical specimen as well as in VAB. | after breast surgery, up to 6 weeks after VAB | 
| false positive rate (FPR) | FNR = rate of patients with falsely diagnosed residual tumor by VAB compared to breast surgery Residual tumor is defined as a positive result; in surgical specimen as well as in VAB. | after breast surgery, up to 6 weeks after VAB | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, vacuum-assisted biopsy, pathological complete response