Diagnosis of Pathological Complete Response by Minimal Invasive Biopsy After Neoadjuvant Chemotherapy in Breast Cancer

Study Overview
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Brief Summary
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The study aims to evaluate the ability of representative vacuum-assisted minimal invasive biopsy (VAB) to diagnose pathological complete response (pCR=ypT0) in breast cancer patients after neoadjuvant chemotherapy (NACT).

Detailed Description
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Neoadjuvant chemotherapy (NACT) is an increasingly used approach for patients with locally advanced and primarily inoperable breast cancer or for patients with potentially chemosensitive tumors. In clinical routine surgical treatment follows the pre-operative chemotherapy. 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. Up to now, prediction of pCR after NACT, i.e. diagnosing a pCR without surgery, is based on tumor biology at diagnosis, the applied NACT regimen and breast imaging results; all with mediocre accuracy. This prospective, monocenter diagnostic trial aims to explore if minimal invasive biopsies (MIB) might overcome this diagnostic challenge. From September 1st, 2014 to February 15th, 2015 the investigators performed ultrasound guided vacuum-assisted minimal invasive biopsy (VAB) on 50 breast cancer patients after NACT and directly prior to surgery. To analyse VAB pathologically results were categorized as follows: residual vital tumor cells (invasive, in situ, both, lymphangiosis carcinomatosous) present, (significant parts of) the tumor bed present, neither vital tumor cells nor (significant parts of) the tumor bed (indicating a non representative VAB). The results were compared to those of the pathological examination of surgical specimen.

Official Title
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Can a Pathological Complete Response in the Breast be Diagnosed by Vacuum-assisted, Ultrasound Guided Minimal Invasive Biopsy After Neoadjuvant Chemotherapy in Breast Cancer Patients? A Proof of Concept From a Prospective Cohort Study

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Procedure: vacuum-assisted biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The investigators included patients after neoadjuvant chemotherapy (NACT) according to the NACT protocol with at least one detectable mass / marker after NACT in ultrasound with cT1c-cT4a-c tumors after informed consent with unilateral or bilateral primary breast cancer, confirmed histologically prior to chemotherapy with known grading, ER/PgR/HER-2neu- and Ki-67 status with breast ultrasound, mammography (and breast MRI where necessary) before and after NACT clinical / imaging partial or complete response to NACT Exclusion Criteria: The investigators excluded patients from the study with NACT <12 weeks because of termination due to progressive disease, massive adverse events or patient wish non-detectable mass in ultrasound / dislocation of marker (> 10mm distance to the initial lesion) cT4d stage (inflammatory breast cancer) M1 stages stable disease according to a multimodal assessment of ultrasound, mammography and breast MRI (if available) according to RECIST

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 |
| --- | --- |
| Experimental: vacuum-assisted biopy<br>All patients enrolled in this study received a vacuum-assisted biopsy before surgery. | Procedure: vacuum-assisted biopsy<br>* Ultrasound guided VAB was used directly prior to breast conserving surgery or mastectomy. It was performed by experienced physicians (> 50 ultrasound guided minimal invasive biopsies per year, > 500 breast ultrasound examination of the breast per year). The needle was placed below or beside the target lesion according to physician's choice. At least six biopsies should be taken; up to 12 according to the physicians choice. After the VAB a clip marker was placed to highlight the position of the biopsy for specimen radiography and pathology.<br>* Other names: vacuum-assisted minimal invasive biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| false negative rate to diagnose a pathological complete response by vacuum-assisted biopsy for the whole cohort and predefined subgroups | As an explorative study, the statistical analysis was performed using descriptive methods only. For a baseline comparison between groups, the investigators compared the group of patients with pCR to the group of patients without pCR. As primary outcomes the investigators calculated negative predictive values (NPV) and false negative rates (FNR) for the whole study cohort as well as for certain subgroups (especially addressing the question of evaluating representativeness of VAB). The investigators calculated two-sided-95% confidence intervals for all results. | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| negative predictive values to diagnose a pathological complete response by vacuum-assisted biopsy for the whole cohort and predefined subgroups | As an explorative study, the statistical analysis was performed using descriptive methods only. For a baseline comparison between groups, the investigators compared the group of patients with pCR to the group of patients without pCR. As primary outcomes the investigators calculated negative predictive values (NPV) and false negative rates (FNR) for the whole study cohort as well as for certain subgroups (especially addressing the question of evaluating representativeness of VAB). The investigators calculated two-sided-95% confidence intervals for all results. | 1 week |