Clip Marker Placement in Primary Lesions of Breast Cancer Patients Receiving Neoadjuvant Therapy

Study Overview
=================
Brief Summary
-----------------
Neoadjuvant systemic therapy (NST) is increasingly recommended for patients with early breast cancer, and the rate of patients with pathological complete remission (pCR) is increasing due to the use of modern chemotherapy regimens and targeted therapies, especially in patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer and triple negative breast cancer (TNBC). It is therefore important to mark a lesion (with e.g. clip) before the start of NST in order to safely identify and localize a clip and (former) tumor bed after completion of NST. Reliable sonographic detection of the clip would be preferred to mammography-guided detection and marking. In addition to avoiding radiation exposure by mammography and reducing time, personnel and financial expenditure, ultrasound-guided wire marking of the clip is less painful for the patient than stereotactic wire marking. The present prospective registry study aims to evaluate how often the intramammary Tumark® Vision clip can be detected by ultrasound after completion of NST in patients with TNBC and HER2+ breast cancer and thus, in the case of pCR, how often the elaborate clipping with mammographic (stereotactic) guidance can be avoided.

Detailed Description
-----------------
Breast cancer patients whose carcinomas have an aggressive tumor biology which implies the need for chemotherapy are increasingly being treated with NST. As a standard procedure, clip placement of the suspicious lesion is performed after ultrasound-guided core biopsy or mammography-guided vacuum biopsy. Clipping is necessary to enable the clear identification of the sonographically suspicious area of the breast and safe surgical removal of the remaining tumor tissue (if any) during a later surgery, even following a good response under NST. The placement of a marker (clip) is particularly important for the precise localization of the original tumor bed in patients with pCR. There are a number of commercially available markers (clips) which are indicated for intramammary marking of a lesion and which differ in terms of shape and material. Difficulties may arise in placing the clip in the tumor or the tumor center. In addition, the clip can dislocate from the initial location and/or the clip might not be visualized during response monitoring. Evaluations of the ultrasound-visible clip made of nitinol investigated in this study showed very good results regarding marker dislocation and visibility within 7 days after inital placement.The clip, which immediately unfolds into a 3-dimensional spherical structure after insertion into the tissue, could be detected by both sonography and mammography in all 50 cases after the intervention; however, long-term data data at follow-up controls during and after NST are not available so far. According to current German guidelines, imaging-assisted wire marking is recommended without restriction before breast conserving surgery for non-palpable lesions. The clip is considered the target lesion for wire marking, which can be done under sonographic or stereotactic control. If the clip is reliably visible on ultrasound (even in patients with pCR), the stereotactic control of wire marking can be omitted. Therefore, the ability to visualize a clip in breast ultrasonography is of great importance. The present multicenter study aims to evaluate the sonographic detection rate of the intramammary Tumark® Vision clips after NST in clinical routine and the proportion of cases in which the clip cannot be detected, and thus the rate of mammography-guided wire markings.

Official Title
-----------------
Prospective, Multicenter Registry Study Evaluating the Feasibility of Ultrasound-guided Clipping of Suspicious Intramammary Lesions in Primary Breast Cancer Patients Receiving Neoadjuvant Therapy (Ultra3Detect)

Conditions
-----------------
Primary Breast Cancer

Intervention / Treatment
-----------------
* Device: Tumark® Vision clip


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: female patient aged ≥ 18 years written informed consent patient's consent to NST suspicious unilateral or bilateral intramammary foci that can be safely identified by ultrasound no evidence of distant metastasis (complete staging does not have to be present at inclusion) indication for breast conserving therapy no prior clip placement in the confirmed intramammary carcinoma patient is able to undergo NST treatment (even if the indication based on tumor biology is not yet available) high compliance and high number of planned relevant surgical interventions in participating study center patient can understand the scope of this prospective registry study Exclusion Criteria: allergy to titanium and/or nickel pregnancy ipsilateral relapse (when NST: no exclusion criterion) prior extensive breast surgery (starting from quadrant resection) inflammatory breast cancer extramammary breast cancer multicentric or multifocal breast cancer patient is not operable patient is already undergoing adjuvant/neoadjuvant therapy inability to understand the purpose of the clinical trial or to comply with study procedures

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| US-guided core biopsy and clip placement<br>Female patients with sonographically suspicious, intramammary foci, scheduled for ultrasound-guided core biopsy and marking of the lesion with the Tumark® Vision Clip | Device: Tumark® Vision clip<br>* Suspicious intramammary lesion is marked with clip<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sonographic detection rate of clip at the time of surgery after completion of NST | Intraoperative detection rate of the clip in patients with HER2+ breast cancer or TNBC after at least 12 weeks of NST treatment | At the time of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of ultrasound-guided clip placements per patient | a) Number of lesions marked with a clip per patient and b) Number of clips per lesion | Immediately after placement of clip | 
| Rate of successful clip placements in the tumor center | Not successful: clip placement technically not possible or clip was placed outside the tumor (indication of the distance from the tumor center in mm) | Immediately after placement of clip | 
| Visibility of the device (Tumark® Vision) cannula | Visibility (very good, good, sufficient or bad) of the cannula during US-guided clip placement | During placement of clip | 
| Complications associated with the application of the clip | e.g. hematoma, infection, dislocation, pain (in patients with or without NST) | Up to 6 months after placement of clip | 
| Sonographic detection rate of clips in patients receiving NST | Detection rate at different time points in all patients receiving NST | Immediately after placement of clip as well as after 4-8, 9-12, 13-26 weeks of NST treatment and preoperatively | 
| Sonographic detection rate of clips in TNBC and HER2+ patients receiving NST | Detection rate at different time points in TNBC or HER2+ breast cancer receiving NST | Immediately after clip placement as well as after 4-8, 9-12, 13-26 weeks of NST treatment and preoperatively | 
| Sonographic detection rate of clips in all patients receiving NST and with pCR | Definition of pCR according to residual cancer burden (RCB) score | Immediately after clip placement as well as after 4-8, 9-12,13-26 weeks of NST treatment and preoperatively | 
| Sonographic detection rate of clips in patients not receiving NST | Subgroup of study population not receiving NST | Immediately after clip placement and preoperatively | 
| Intraoperative detection rate of the clip in specimen radiographs | Detection of clip in surgical specimen from the breast subjected to radiography | At the time of surgery | 
| Intraoperative detection rate of the clip on specimen utrasound images | Detection of clip in surgical specimen from the breast subjected to ultrasonography | At the time of surgery | 
| Proportion of patients requiring preoperative, mammography-guided wire marking | If ultrasound-guided wire marking is not feasible, mammography-guided wire marking is performed | Preoperatively | 
| Proportion of patients with mammographic verification after sonographic wire-marking | If ultrasound-guided wire marking is inconclusive | Preoperatively | 
| Proportion of patients with artifacts caused by clips | On ultrasound and/or mammography images | Up to 6 months after placement of clip | 
| Number of patients with complete pathological remission | ypT0/is, ypN0 status after histological evaluation (according to Residual Cancer Burden [RCB] score) of Symmans (2007) | Up to 10 weeks after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast cancer, clip, ultrasound, neoadjuvant therapy