Primary Operation in SYnchronous meTastasized InVasivE Breast Cancer

Study Overview
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Brief Summary
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Primary Operation in synchronous metastasized invasive breast cancer to evaluate the use of local therapy

Detailed Description
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This study is a prospective, randomized, multicentre, study concerning the influence of local treatment on the patients with synchronous metastasized breast cancer. Patients will be stratified at inclusion according to the centre, the menopausal status (pre-menopausal, post-menopausal), the hormone-receptor status (ER-/PR-/not determinable; any PR and/or Er+), the HER-2 status (positive vs. negative/not determinable), the grading (G1/G2/not determinable vs. G3), location of metastases (visceral ± vs bone only), organs with metastases (single organ vs multiple organs) and use of first line chemotherapy (anthracycline ± vs. taxane vs others). Thereafter patients will be randomly assigned to receive either local therapy of the breast (lumpectomy or mastectomy + axillary surgery /± radiotherapy) versus no local therapy. Systemic therapy will be administered at the centers policy.

Official Title
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Primary Operation in SYnchronous meTastasized InVasivE Breast Cancer, a Multicenter Prospective Randomized Study to Evaluate the Use of Local Therapy

Conditions
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Synchronous Metastasized Breast Cancer, Circulating Tumor Cells

Intervention / Treatment
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* Procedure: Surgery
* Procedure: Surgery on Demand


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients age ≥ 18 years Eastern Cooperative Oncology Group Performance Status is 0 -2 Untreated synchronous metastasized invasive carcinoma of the breast with the primary tumor in situ (bilateral synchronous metastasized breast cancer patients are eligible) The primary tumor must be identified and may be any size, however, primary resection with resection free margins must be possible Invasive adenocarcinoma of the breast on histological examination The metastatic site must be identified by radiological assessment(Computer Tomography of the chest and the abdomen OR ultrasound and chest x ray for visceral metastases; bone scan AND/OR computer tomography AND/OR magnetic resonance for bone metastases). A biopsy is not necessary. Written informed consent must be obtained and documented prior to beginning any protocol specific procedures and according to local regulatory requirements able to comply with the protocol requirements during the treatment and follow-up period. Exclusion Criteria: Patients in whom a R0 resection (microscopic free margins) is clinically questionable Inflammatory cancer Patients with a brain metastasis Patients who are not eligible for general anesthesia and operations Patients without metastatic breast cancer (patients with a tumor marker value (CEA, CA15-3) above normal levels without the radiological proven evidence of metastases are not eligible for the study) Patients with a second untreated malignancy Any previous malignancy treated with curative intent and the patient has not been disease-free for 5 years - exceptions are: (a)carcinoma in situ of the cervix, (b)squamous carcinoma of the skin, (c)basal cell carcinoma of the skin Patients with any recurrent cancer disease Pregnant or lactating women Patients are not allowed to be part of another local therapy trial

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: A: Surgical Therapy<br>Local therapy consists of lumpectomy or mastectomy with or without radiotherapy (according to center tumor board decision) with a resection free margin of at least 1 mm or more demonstrated on paraffin embedded histological sections. Intraoperative frozen sections are allowed but not definitive for margin assessment. Sentinel node biopsy may be performed and has always to be followed by axillary dissection of level I and II (axillary surgery level I and II is mandatory). | Procedure: Surgery<br>* lumpectomy or mastectomy with or without radiotherapy. Sentinel biopsy followed by axillary dissection (level I-II)<br>|
| Other: B: Surgery on Demand<br>In Arm B (no local therapy) it may be necessary to perform local therapy on demand (surgery, radiotherapy). Reasons may be uncontrolled bleeding or infected exulcerations with a septic component and no treatment benefit from conservative therapy. This will be considered as protocol deviation. However, the patient's follow up is recorded and data are available for analyses as intention to treat. | Procedure: Surgery on Demand<br>* if necessary local therapy on demand<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to evaluate the median survival of patients with synchronous metastasized breast cancer and the primary tumor in place comparing arm A with local therapy to the primary tumor versus arm B without local therapy |  | time point at which 50% of all randomized patient died | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to distant progression (TTPd) |  | Time to treatment change due to systemic progression | 
| time to local progression (TTPl) |  | Increase in size >25% of the primary tumor in arm B (no local therapy). Local recurrence in arm A (local therapy). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, ABCSG, POSYTIVE, growth factor, median survival, surgery on demand, surgical therapy, blood specimen, tissue specimen, VEGF, TGF, circulating tumor cells, stem cells