Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Each patient will perform 13 study visits, and at each visit, all necessary study procedures will be performed according to the clinical investigation plan:

* Screening
* Pre-surgery treatment
* Surgery and study device implant
* Post-surgery follow-up

REGENERA breast implant implantation

Margherita Tamplenizza

Mario Rietjens

Manuela Roncella

Benigno Acea Nebril

The goals of this clinical trial are:

* demonstrate the safety of REGENERA breast implant in patients undergoing lumpectomy of malignant breast lesions
* demonstrate the safety and performance of REGENERA in terms of investigator's satisfaction, potential interference with current standard-of-care imaging techniques and occurrence of device-related serious adverse events.

Participants will perform 13 study visits, and at each visit, all necessary study procedures will be performed according to the clinical investigation plan:

* Screening
* Pre-surgery treatment
* Surgery and study device implant
* Post-surgery follow-up up to 5 years

Clinical Trial to Demonstrate the Safety and Performance of REGENERA Breast Implant in 40-70 Years Old Women Affected by Malignant Breast Lesion Treated by Lumpectomy

A Pivotal Study of REGENERA Implant in Malignant Breast Lesion Treated by Lumpectomy

The rate of AEs with a causal relationship to REGENERA should be \<5% at 3 months after implant.

At least 7 in a 0-10 Visual Analogue Scale, VAS.

At least 40 in an "ad hoc" questionnaire (12-60 scale).

An imaging evaluation questionnaire will be provided for investigators to fill out.

The rate of REGENERA-related SAEs should be \<5% at each follow-up after 3 months and up to 18 months.

The rate of REGENERA-related SAEs should be \<7% at each follow-up after 18 months and up to 5 years.

Tensive SRL

Females ≥ 30 years of age with a diagnosis of invasive breast cancer or ductal carcinoma in situ (DCIS), scheduled for BCS +/- SLNB or ALND

The Lightpoint EnLight beta particle detector is an investigational non CE-marked medical device

EnLight

The LightPath Imaging System is an investigational non CE-marked in vitro diagnostic device

LightPath

Anand D Purushotham, MBBS FRCS MD

Maarten Grootendorst

Anand D Purushotham

This study will correlate the resection margin status of the breast cancer tumour (WLE specimen), cavity shavings (if any) and breast cavity, and the metastatic status of axillary lymph nodes as determined by EnLight, LightPath, and histopathology. This is a pilot study to assess feasibility before proceeding to a pivotal study to evaluate the use of these imaging systems in clinical practice.

This is a prospective, single centre, pilot study to assess the feasibility of the EnLight and LightPath Imaging Systems for intra-operative analysis of tumour margins and axillary lymph nodes in breast conserving surgery (BCS) for breast cancer.

Female patients with a diagnosis of invasive breast cancer or DCIS scheduled to have BCS +/- sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) will be screened, and enrolled in the study if eligible and willing to give written informed consent.

BCS only

Subjects scheduled to have BCS only will receive 5 MBq/kg of 18F-FDG, up to a maximum 300 MBq. 18F-FDG will be administered intravenously in the Nuclear Medicine Department, 60-180 minutes prior to EnLight and LightPath imaging.

After resection, the WLE specimen will be examined with the LightPath Imaging System. The WLE specimen will then be imaged with the EnLight Imaging System. The LightPath Imaging System will be located in a room next to the operating theatre, to allow "real-time" imaging to be performed. If a positive signal is detected with the EnLight Imaging System ("EnLight positive") or the LightPath Imaging System ("LightPath positive") the surgeon will perform cavity shavings of the positive area (up to a maximum thickness of 10mm). After resection, the shavings (if any) will be examined with the EnLight and LightPath Imaging Systems. A member of the research team who is not the operating surgeon will operate the LightPath Imaging System.

The EnLight will be used by the surgeon to image the surgical cavity post WLE. If the surgeon detects a positive signal with the EnLight, s/he will perform cavity shavings of the beta positive area (up to a maximum thickness of 10mm). All cavity shavings will be examined with the EnLight and LightPath Imaging Systems and then sent for histopathological analysis.

Sutures and/or surgical clips will be placed on the WLE specimen and cavity shavings (if performed) to record the anatomical orientation, as per standard practice. Positive signals on the resected WLE specimen and cavity shavings (if performed) will be marked by the surgeon with a prolene suture to facilitate accurate correlation with histopathology. If two or more positive signals are detected, multiple prolene sutures will be used.

BCS plus SLNB

Subjects scheduled to have BCS plus SLNB will receive 150 MBq 99mTc nanocolloid and 5 MBq/kg 18F-FDG, up to a maximum of 300 MBq. 99mTc nanocolloid will be injected periareolarly in the Nuclear Medicine Department prior to surgery. 18F-FDG will be administered intravenously in the Nuclear Medicine Department, 60-180 minutes prior to the estimated start of EnLight and LightPath imaging. The gamma probe will be used before and after the injection of 18F-FDG to identify and localise 99mTc SLN uptake transcutaneously. The findings before and after 18F-FDG injection will be compared to make sure 18F-FDG does not mask extraordinarily low active sentinel nodes. It is important to emphasize that we do not expect this to occur. Blue dye will be injected intra-operatively as per standard procedure.

BCS will be performed as described in section 'BCS only'.

As per standard practice the gamma probe and blue dye will be used to identify SLNs. Prior to dissection of the SLNs, the EnLight will be used by the surgeon to image the SLNs in vivo. All excised SLNs will be imaged with the EnLight and subsequently in the LightPath Imaging System at the time of the surgical procedure.

Following dissection of SLNs, the surgeon will scan the axilla with the EnLight to identify lymph nodes that are non-blue, non-palpable and gamma probe negative, but EnLight positive. EnLight positive lymph nodes will be excised and imaged with the EnLight and subsequently the LightPath Imaging System. As per SLNB standard of care the maximum number of lymph nodes that will be excised will be four in total.

The LightPath Imaging System will be located in a room next to the operating theatre, to allow "real-time" imaging to be performed. The EnLight positive and/or LightPath positive SLNs will be clearly labelled in order to facilitate correlation with histopathology.

BCS plus ALND

Subjects scheduled to have BCS plus ALND will receive 5 MBq/kg of 18F-FDG, up to a maximum 300 MBq. 18F-FDG will be administered intravenously in the Nuclear Medicine Department, 60-180 minutes prior to the estimated start of EnLight and LightPath imaging.

BCS will be performed as described in section 'BCS only'.

The surgeon will palpate the ALND specimen prior to complete resection to identify any palpable nodes. If present, palpable nodes will be imaged in vivo with the EnLight. The ALND specimen is then excised as per standard practice. The surgeon will examine the excised ALND tissue with the EnLight, and EnLight positive lymph nodes will be dissected from the ALND specimen. The maximum number of lymph nodes to be dissected from the ALND specimen will be four. All dissected lymph nodes will be imaged ex vivo with the EnLight and subsequently in the LightPath Imaging System at the time of the surgical procedure. The dissected lymph nodes will be sent separately for histopathological analysis to correlate the imaging findings with histopathology.

The LightPath Imaging Systems will be located in a room next to the operating theatre, to allow "real-time" imaging to be performed. The EnLight and/or LightPath positive SLNs will be clearly labeled in order to facilitate correlation with histopathology.

Histopathology of WLE specimen, shavings and lymph nodes

Following EnLight and LightPath imaging, the WLE specimen will be examined according to standard of care histopathology analysis. Details of tumour dimensions along with other histopathology minimum dataset items will be recorded. Additional sections of EnLight positive and/or LightPath positive areas that are marked with a prolene suture will be taken to facilitate accurate histopathology correlation. The additional sections will not affect standard of care histopathology analysis. The distance from the tumour to all six margins (medial, lateral, superior, inferior, anterior and posterior) will be recorded. A margin will be classified as positive if there is either invasive carcinoma within 1mm or DCIS within 2mm of the specimen surface as per current practice in the institution. Histopathology analysis will be performed on any tissue shavings obtained as a result of EnLight and/or LightPath imaging.

Lymph nodes will be examined according to standard of care histopathology analysis. The presence of any metastatic disease will be recorded and classified as macrometastasis (≥ 2 mm), micrometastasis (\< 2 mm to \> 0.2 mm) or isolated tumour cells (≤ 0.2 mm).

EnLight and LightPath imaging must be performed without unnecessary delay, and following the acquisition times set out in the IFU, in order to avoid any degradation in specimen quality prior to transfer to the tissue bank / pathology department for routine analyses.

Details of any adverse events will be recorded.

An ease of use questionnaire will be completed by the operators using the EnLight and LightPath, and by those interpreting recorded EnLight and LightPath images.

Radiation dosimetry

Staff in the Nuclear Medicine department will be monitored as per standard practice. Throughout the surgical procedure, all staff in the operating theatre will wear instant readout and monthly badge dosimeters. Staff handling the surgical specimens will also wear ring dosimeters. Staff caring for the subject in the recovery area will wear monthly badge dosimeters. Pathology staff processing the WLE and lymph node specimens will wear monthly badge and ring dosimeters.

Follow-up

Subject participation ends at the conclusion of the surgical procedure. Adverse events will be recorded until discharge, or for 24 hours after the first study procedure, whichever is sooner.

The Breast Surgery EnLight and LightPath Imaging System Study

A Pilot Study to Evaluate Molecular Imaging Using a BetaScope and a Specimen Analyser for Determining Margin and Lymph Node Status During Breast Conserving Surgery in Women With Breast Cancer

The objective of this study is to assess the feasibility of the EnLight and LightPath Imaging Systems for intra-operative analysis of WLE specimens, the post-resection surgical cavity, shavings (if any) and axillary lymph nodes in vivo and ex vivo. This will be assessed by examining the following secondary outcome measures

Guy's and St Thomas' NHS Foundation Trust

King's College London

Lightpoint Medical Limited

Pharmaceutical Solutions

All Drugs and Chemicals

Technetium Tc 99m Sulfur Colloid

Radiopharmaceuticals

Participants receive technetium Tc-99m sulfur colloid injection and undergo lymphoscintigraphy according to clinical practice. Prior to surgery, participants also receive indocyanine green solution subdermally close to the tumor or into subareolar region of the breast skin. Participants then undergo Axillary Lymph Node Biopsy and surgery.

Indocyanine Green Solution

Technetium Tc-99m Sulfur Colloid

This is a method used to check the lymph system for disease. A radioactive substance that flows through the lymph ducts and can be taken up by lymph nodes is injected into the body. A scanner or probe is used to follow the movement of this substance on a computer screen. Lymphoscintigraphy is used to find the sentinel lymph node (the first node to receive lymph from a tumor), which may be removed and checked for tumor cells. Lymphoscintigraphy is also used to diagnose certain diseases or conditions, such as lymphoma or lymphedema.

Lymphoscintigraphy

Axillary Lymph Node Biopsy

Stephen Grobmyer, MD

This clinical trial will enroll up to 130 adult women with a confirmed diagnosis of clinical stage 1 or 2 breast cancer who are undergoing breast cancer surgery with lumpectomy or mastectomy and planned axillary sentinel node biopsy procedure. Participants will undergo lymphatic mapping with technetium Tc-99m (99mTc) sulfur colloid in accordance with routine clinical practice. Injections of 99mTc sulfur colloid will take place the afternoon prior to planned next morning surgery or on the morning of surgery. Participants will undergo lymphoscintigraphy in accordance with standard clinical practice.

Immediately prior to operation, after the induction of anesthesia in the operating room, up to 1cc of 0.5% indocyanine green (ICG) solution will be injected subdermally close to the tumor or into the subareolar region after disinfection of the breast skin. ICG movement will be facilitated by manual massage and monitored with fluorescence imaging. ICG fluorescence will be elicited and detected by Photodynamic Eye (PDE) camera. The lymphatic drainage, made evident by the fluorescent dye, will be monitored in real time on a monitor. The fluorescence will be followed towards the armpit region (axilla) and time for the fluorescence to reach the axilla will be recorded. Following standard practice, an incision will be made in the armpit region. Fluorescent lymph nodes (ICG positive) will be localized and removed and analyzed by a pathologist. Node removal will continue until no residual fluorescence is visible in the axilla. Removed nodes will be tested for radioactivity using a standard gamma-detecting probe and the counts per minute will be recorded. Finally, the armpit region will be inspected with the gamma probe to determine if there are any residual radioactive nodes. Residual sentinel nodes (the first node to receive lymph from a tumor) will be removed. For the purposes of this study, the sentinel status of a node will be defined as being flagged as sentinel by either one or both of the ICG or 99mTc methods. The goal of the project is to confirm that axillary lymphatic mapping with ICG leads to similar nodes being labeled as sentinel as lymphatic mapping with 99mTc-labeled radiotracer.

PRIMARY OBJECTIVES:

I. To confirm that axillary lymphatic mapping with indocyanine green solution (ICG) solution leads to a similar number of nodes being labeled as sentinel as lymphatic mapping with 99mTc-labeled (technetium Tc-99m sulfur colloid) radiotracer.

OUTLINE:

Participants receive technetium Tc-99m sulfur colloid injection and undergo lymphoscintigraphy according to clinical practice. Prior to surgery, participants also receive indocyanine green solution subdermally close to the tumor or into subareolar region of the breast skin. Participants then undergo axillary sentinel node biopsy and surgery.

Comparison of Use of Indocyanine Green and 99mTc-labeled Radiotracer for Axillary Lymphatic Mapping in Patients With Breast Cancer

Let A be the number of Tc-positive and ICG-positive sentinel nodes (SNs) detected, B be the number of Tc-positive and ICG-negative SNs detected, and C be the number of Tc-negative and ICG-positive SNs detected. The total number (N) of SNs detected is therefore N = (A + B + C); the proportion of SNs detected by the Tc method (PTc) is (A + B)/N; and the proportion of SNs detected by the ICG method (PICG) is (A + C)/N. Differences in the proportions of SLNs flagged will be compared using a two-sided 95% confidence interval.

National Cancer Institute (NCI)

Mitaka USA, Inc.

Case Comprehensive Cancer Center

Diagnostic (Indocyanine Green, 99mTc-labeled Radiotracer)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Tc-positive and ICG-positive sentinel nodes (SNs)

Tc-positive and ICG-negative sentinel nodes (SNs)

Tc-negative and ICG-positive SNs

Total sentinel lymph nodes (SLNs)

Dr. Stephen Grobmyer

Proportion of SNs (PTc) detected by Tc method

Proportion of SNs (PICG) detected by ICG method

Proportion of Sentinel Lymph Nodes (SLNs) Flagged by the Two Methods

Overall Study

Diseases and Abnormalities at or Before Birth

Congenital Abnormalities

Participants will receive an autologous fat graft to correct either a benign breast deformity or a post segmental mastectomy deformity.

Autologous Fat Graft

J. Peter Rubin, MD

The investigators will assess changes in breast appearance, graft retention and quality of life over one year in patients who have received direct autologous adipose tissue injection for the treatment of objectionable post-surgical breast deformities. These patients have undergone the resection of breast tissue to treat either benign or malignant breast disease.

During the past decade there has been increased awareness of the potential of free adipose cell grafting to treat a variety of problems in both reconstructive and cosmetic plastic surgery. There have been encouraging reports describing the use of autologous fat grafts (fat tissue harvested by standard liposuction techniques in a given patient and then re-injected at another site) for treating breast deformities in the setting of benign and previously treated malignant breast problems.

There has been a corresponding large scale laboratory investigation effort into the potential of adipose derived stem cells (ADSC's) harvested during liposuction and induced to differentiate into various cell types in the mesenchymal cell line. The potential clinical utility of these cells in the treatment of patients who present with a breast deformity after segmental mastectomy (lumpectomy) and radiation therapy has been described, but not studied in rigorous prospective manner.

The investigators believe that the clinical use of these autologous fat cell grafts have unique advantages in the treatment of breast deformities. The technique is minimally invasive, easily repeated and is associated with minimal surgical morbidity (indeed it may have the advantage of improving the appearance of both the breast deformity and the area from which they are harvested), it typically displays a rapid recovery, a complication rate that is no greater (and probably less than ) established and currently used surgical treatment(s) of these breast problems, and is oncologically safe.

Treatment of Benign Breast Deformities and Post-Segmental Mastectomy Breast Deformities With Autologous Fat Grafting (AFT)

Preadipocyte yield: The number of cells isolated per gram of adipose tissue will be determined using a hemacytometer.

Preadipocyte Viability: Cell viability will be determined using the Live/Dead assay.

Preadipocyte Proliferation: Cellular proliferation of preadipocytes will be assessed with the CyQUANT Cell Proliferation Assay Kit (Invitrogen, Carlsbad, CA) at 48 and 96 hours.

Preadipocyte Differentiation: The assessment of the potential of the preadipocytes to differentiate into adipogenic cell types will be assessed

Assess breast appearance and soft tissue volume before and after autologous fat grafting utilizing 2D / 3D digital photography and a physician rating scale to determine graft retention through 12 months following fat grafting procedure.

Measure patient satisfaction with use of quality of life questionnaires (SF-36 and BREAST-Q) before and after autologous fat grafting.

University of Pittsburgh

Principal Investigator

Coagulants

Hemostatics

Randomized application of 3g haemostatic powder (HaemoCer) in the wound site during breast-conserving surgery.

HaemoCer

Christian Singer, Prof.

HaemoCer is a hemostatic agent to control bleedings during surgical procedures by accelerating natural hemostasis and is frequently applied during breast conserving surgery in women with breast cancer. There is however no adequate data available on the efficacy of HaemoCer regarding seroma formation or drainage output. The objective of this study is to investigate whether the intraoperative application of haemostatic powder (HaemoCer) in breast-conserving surgery in breast cancer patients reduces the postoperative drainage output and number of days until drain removal (number of hospitalization days).

HaemoCerTM Application in Breast Cancer Surgery

Randomised Controlled Trial: HaemoCerTM Versus no HaemoCerTM in Breast Cancer Surgery to Reduce Postoperative Drainage Output

Medical University of Vienna

Univ.-Prof. Dr.med.univ. MPH

Peer Christiansen, DMSc, Prof.

The challenge of breast conserving surgery (BCS) is to obtain free resection margins, by removing the invasive tumor and the precursor cells: DCIS (Ductal Carcinoma in Situ). Consequently, 17%-25% of primary invasive breast cancer patients will need a repeat surgery. Repeat breast surgery has been associated with higher surgical risks, poorer cosmetic outcome and increased psychological and economic burden. Finding a precise method to obtain tumor- and DCIS-free resection margins during BCS is therefore strongly needed.

The purpose with this study is to investigate if the need for a re-operation can be reduced by performing Digital Breast Tomosynthesis (DBT) of the resected tumor margins compared to the currently used standard X-ray during BCS.

Background Breast cancer is the most common type of cancer in Denmark with approximately 4700 new cases each year, with an increased incidence during the last decades. Almost 70% of the patients are treated with breast conserving surgery (BCS) and breast irradiation. Unfortunately, 5.9 % of the patients treated with BCS will experience local recurrence after 9 years. The strongest predictor for local recurrence is a positive pathologic resection margin. Therefore it is important intraoperatively to be able to evaluate the margin width of the resected specimen precisely. The challenge during BCS is to remove the primary invasive breast cancer, with negative resection margin, free of invasive tumor and DCIS, Ductal Carcinoma In Situ. Some have concluded that lack of accurate imaging especially of the DCIS is the main reason for positive margins and repeat surgery, as the DCIS often, but not in all cases, contains microcalcifications that can be detected on mammography (x-ray of the breast). Consequently, 17%-25% of the patients will need a second or a third surgery. Repeat surgery has been associated with higher surgical risk, poorer cosmetic outcome, and increased psychological and economic burden for both patients and the society. Finding an optimal imaging method to obtain adequate resection margins close to or during BCS that can reduce the number of repeat surgeries, is therefore strongly needed.

Definition of resection margin status

A safe macroscopic surgical resection margin is, according to the Danish Breast Cancer Group´s (DBCG) guidelines, defined as a margin width ≥ 5mm minimizing the risk of leaving residual tumor. In many institutions in Denmark, a perioperative evaluation of the tumor is performed as a macroscopically assessment by a pathologist. This is a ressource demanding procedure and X-ray of the specimen is used instead. A radiological, positive resection margin is defined as a margin width of 0 mm, that leads to a re-excision during the same surgical procedure, and additional breast tissue is removed at the exact same area of the patient's breast. This procedure aims to avoid the discomfort of a repeat surgery. The perioperative radiological assessment of the resection margins is afterwards confirmed microscopically, where a positive margin at our institution is defined as "tumor on ink", meaning tumor cells in the inked resection margin with 0 mm to the margin. A positive margin will trigger a repeat surgery, either a new BCS or a mastectomy where the whole breast is removed. For DCIS, a margin-width of less than 2 mm is considered positive, and the patient will be offered repeat surgery according to guidelines. A distance from the invasive carcinoma to the resection margin of \< 2 mm, but not "on the ink" is surgical considered sufficient and the patient will according to DBCG guidelines, not require a repeat surgery, but will instead be offered additional boost to the subsequent radiotherapy. The result of the final histopathology is, however, not available until 7 workdays after the initial BCS. Guidance of a more optimal perioperative methods to evaluate the resection margins during BCS would, therefore, be highly desirable, and could potentially lead to a decreased rate of repeat surgery and hence save several patients from the discomfort of a second surgical procedure.

Intraoperative imaging methods for margin assessment

Various methods to assess resection margins have been investigated such as frozen section analysis, imprint cytology, macroscopically evaluation and imaging with x-ray, micro-CT scanning or ultrasound of the resected tumor margins. All have, however, their limitations, either because they are time consuming, or simply because they are not accurate enough to predict resection margin status. The imaging modality X-ray has been reported in several studies to have a high specificity, predicting negative margins up to 95%, but unfortunately a low sensitivity of only 21%. That means that the method is particularly good to predict a negative margin. The X-ray is less sensitive when it comes to predict a positive resection margin, with the final histopathology as a reference method. The lower sensitivity is due to the fact, that x-ray has difficulties, when it comes to detect the breast tumor in a very dense normal breast tissue, most common for young women. The X-ray evaluation also has the disadvantage of only delivering a 2D solution to a 3D problem. The other imaging method currently in use is ultrasound that has a high sensitivity of 80% but a low specificity of 59% to predict positive resection margins (Ramos M. et al).

A new method called Micro-CT (micro-Computed Tomography) can provide 3D imaging of the resected tumor and the microcalcifications that helps to asses all margins of the resected tumor. Unfortunately, there is a high interobserver variability reported with this method. Furthermore, it is difficult to differentiate between tumor and normal breast tissue in the resected margins in some of the cases, which makes it impossible for the radiologist to determine if the margins are positive or negative. This may be one of the reasons for, why this method does not perform so well with a sensitivity range of only 38%-56%.

Digital Breast Tomosynthesis (DBT) is a novel method for assessment of resection margins based on X-ray technology. DBT provides images of the resected tumor with a large field of view of the specimen and a high resolution, that allows the radiologist to examine the resected specimen in one millimeter increments both in 2D and 3D, where the extent and the shape of the tumor and the microcalcifications are better defined than on conventional 2D mammography. Only few clinical studies have investigated DBT for evaluation of resection margins with the most recent study with 98 patients included (Park KU. et al). This study reported a high performance of the DBT with a sensitivity to predict positive margins of 93%, and a specificity of 78%, to predict negative margins, with the final histopathology as a reference method.

Objectives

The overall objective of the present study is to investigate if adequate resection margins can be obtained with use of DBT of the resected margins during BCS to reduce the rate of repeat surgery and avoid further unnecessary complications and psychological stress for the patients.

Hypothesis

Does intraoperative DBT improve assessment of the resected margins compared to standard method with X-ray? The final histopathology will be used as a reference method.

1. DBT can contribute to obtain negative resection margins and thereby reduce the need of repeat surgery as compared to X-ray.
2. The performance of DBT predicting resection margin status is more accurate compared to the standard method with X-ray.

Study participants

The study participants will be recruited at the Department of Plastic and Breast Surgery at Aarhus University Hospital after they have been diagnosed with operable invasive breast cancer and scheduled for BCS. The study participants will receive separate information leaflet about this project that respects the applicable regulatory requirements. The page describing the rights of the patient participating in a health research project will also be handed out to the patient by the breast surgeon. The breast surgeon will obtain the informed consent from the patient and mention in the patient's medical record, that the patient has given consent to participate in this project.

Randomization

The study participant will be randomized to either the DBT or the standard method (X-ray) by the breast surgeon in the system REDCap®. REDCap® is a secure web platform that can build and manage online databases and surveys that will also be used for the data management of this project. The randomization will be performed by the breast surgeon during the first consultation with the patient, as soon as the patient has given oral and written consent and is included in each trial.

Handling of the resected breast tumor

The study encompasses tissue being procured as part of the normal diagnostic procedure. The material will, as all tissue collected for diagnostic purposes, be kept in the existing clinical biobank at the Department of Pathology, at Aarhus University Hospital during as well as after the closure of the study. A research biobank will therefore not be established

Safety

There are no side effects and no risk of radiation for the investigators in the DBT-trial, as the resected tumor will be located inside the DBT or in the X-ray that is a closed system, ex-vivo, with no radiation exposure to the technical staff or to the study patients.

Statistics and analysis

A sample size of 123 study participants was calculated as necessary to detect a reduction from 20% in the X-ray-group to 7% in the DBT-group with a statistical power of 80% and a 5% level of significance. The investigators expect a few patients may drop-out for different reasons, and estimated that a total number of 250 patients are enough to be included in the DBT-trial.

The statistical analyses and calculation will be made primarily by the investigator Irina Palimaru Manhoobi (IPM) using STATA® where after the work will be reviewed by a statistician to ensure a high quality of the statistical work.

1. The occurrence of positive resections margins, re-excisions and repeat surgery will be compared between groups using the Fisher exact test.
2. The performance of the tested and the standard method: The sensitivity, specificity, Positive Predictive Value (PPV) and the Negative Predictive Value (NPV) compared to the reference method will be calculated with the McNemar Chi-Square test.

A two-sided p-value of less than 0.05 will be considered statistically significant.

Data management

The study participants will be identified from the Central Personal Register system (CPR) with permission obtained the 1st of April 2020 from the Danish Data Protection Agency (DDPA) / "Region Midtjyllands interne fortegnelse over forskningsprojekter" with case number 1-16-02-141-20. The informed consent from all study participants gives the investigator, sponsor and the representants of the sponsor, the direct access to the below described clinical data from the medical record (EPJ) Electronical Patient Journal, that is important to perform this project. All clinical data will be transferred anonymously to the secure web application for data management in "RedCap" that is administered by Aarhus University. The investigator IPM is responsible for the data management. The study is in according to the guidelines of the Helsinki Declaration II, GCP guidelines and the Danish Legislation regarding clinical trials and legislation regarding personal data.

Digital Breast Tomosynthesis (DBT) to Improve Assessment of Resection Margins in Invasive Breast Cancer

Optimal Imaging Methods to Reduce Repeat Surgery in Invasive Breast Cancer

The number of patients with one or more positive resection margins in the final histopathology.

The number of patients that recieves further excision of the cavity wherefrom the breast tumor is resected, during the initial breast conserving surgery.

The number of patients that recieves a second or a third surgery due to insufficient resection margins during initial primary breast conserving surgery.

Sensitivity, specificity, positive and negative predictive value and accuracy of the tested method to predict accurate resection margin status.

The weight of the re-excised breast tumor during initial breast conserving surgery to see if there is a difference of how much tissue is removed with the tested method DBT and the standard X-ray method.

The type of repeat surgery, either breast conserving surgery or mastectomy where the whole breast is removed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Trial to Demonstrate the Safety and Performance of REGENERA Breast Implant in 40-70 Years Old Women Affected by Malignant Breast Lesion Treated by Lumpectomy	NCT05941299	Mastectomy, Seg... Breast Neoplasm...	REGENERA breast...	40 Years - 70 Years	Tensive SRL
The Breast Surgery EnLight and LightPath Imaging System Study	NCT02151071	Breast Neoplasm...	EnLight LightPath	30 Years -	Lightpoint Medical Limited
Comparison of Use of Indocyanine Green and 99mTc-labeled Radiotracer for Axillary Lymphatic Mapping in Patients With Breast Cancer	NCT02419807	Stage I Breast ... Stage II Breast...	Indocyanine Gre... Technetium Tc-9... Lymphoscintigra... Axillary Lymph ...	-	Case Comprehensive Cancer Center
Treatment of Benign Breast Deformities and Post-Segmental Mastectomy Breast Deformities With Autologous Fat Grafting (AFT)	NCT01756092	Breast Cancer Lumpectomy Mastectomy, Seg...	Autologous Fat ...	18 Years - 70 Years	University of Pittsburgh
HaemoCerTM Application in Breast Cancer Surgery	NCT04811378	Breast Neoplasm... Mastectomy, Seg...	HaemoCer	18 Years - 99 Years	Medical University of Vienna
Digital Breast Tomosynthesis (DBT) to Improve Assessment of Resection Margins in Invasive Breast Cancer	NCT04478669	Invasive Breast... Mastectomy, Seg... Margins of Exci...		19 Years -	Aarhus University Hospital
Treatment of Benign Breast Deformities and Post-Segmental Mastectomy Breast Deformities With Autologous Fat Grafting (AFT)	NCT01756092	Breast Cancer Lumpectomy Mastectomy, Seg...	Autologous Fat ...	18 Years - 70 Years	University of Pittsburgh
Digital Breast Tomosynthesis (DBT) to Improve Assessment of Resection Margins in Invasive Breast Cancer	NCT04478669	Invasive Breast... Mastectomy, Seg... Margins of Exci...		19 Years -	Aarhus University Hospital
Digital Breast Tomosynthesis (DBT) to Improve Assessment of Resection Margins in Invasive Breast Cancer	NCT04478669	Invasive Breast... Mastectomy, Seg... Margins of Exci...		19 Years -	Aarhus University Hospital

Spots Global Cancer Trial Database for mastectomy, segmental