NCT01015625.

Trial name or title	Primary Operation in SYnchronous meTastasized InVasivE Breast Cancer (POSYTIVE)
Methods	Randomised clinical trial Austrian Breast & Colorectal Cancer Study Group 254 patients May 2010 to May 2019
Participants	Inclusion criteria: Patients aged ≥ 18 years Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2 Untreated synchronous metastasised invasive carcinoma of the breast with the primary tumour in situ (bilateral synchronous metastasised breast cancer patients are eligible) The primary tumour 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 (CT of the chest and the abdomen OR ultrasound and chest X‐ray for visceral metastases; bone scan and/or CT and/or MRI 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 an R0 resection (microscopic free margins) is clinically questionable Inflammatory cancer Patients with a brain metastasis Patients who are not eligible for general anaesthesia and operations Patients without metastatic breast cancer (patients with a tumour marker value (CEA, CA15‐3) above normal levels without 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: carcinoma in situ of the cervix; squamous carcinoma of the skin; 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.
Interventions	Local therapy consists of lumpectomy or mastectomy with or without radiotherapy (according to centre tumour 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 must always be followed by axillary dissection of level I and II (axillary surgery level I and II is mandatory).
Outcomes	Primary outcome measure: to evaluate the median survival of patients with synchronous metastasised breast cancer and the primary tumour in place comparing arm A with local therapy to the primary tumour versus arm B without local therapy [ Time Frame: time point at which 50% of all randomised participants died ] [ Designated as safety issue: No ] Secondary outcome measures: time to distant progression [ Time Frame: time to treatment change due to systemic progression ] [ Designated as safety issue: No ] time to local progression [ Time Frame: increase in size > 25% of the primary tumour in arm B (no local therapy). Local recurrence in arm A (local therapy). ] [ Designated as safety issue: No ]
Starting date	May 2010
Contact information	florian.fitzal@meduniwien.ac.at, michael.gnant@meduniwien.ac.at
Notes