Primary Operation in SYnchronous meTastasized InVasivE Breast Cancer

NCT01015625 | Completed Results

• 2 other identifiers: ABCSG 28 / POSYTIVEABCSG 28
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 14

Brief Summary

Primary Operation in synchronous metastasized invasive breast cancer to evaluate the use of local therapy

Conditions

Synchronous Metastasized Breast Cancer; Circulating Tumor Cells

Keywords

breast cancer; ABCSG; POSYTIVE; growth factor; median survival; surgery on demand; surgical therapy; blood specimen; tissue specimen; VEGF; TGF; circulating tumor cells; stem cells

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall Survival with vs without local therapy (surgery)

  Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months

Secondary Outcomes (2)

• Time to Distant Progression

  Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months

• Time to Local Progression (TTPl)

  Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months

Study Arms (2)

A: Surgical Therapy

OTHER

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

B: Surgery on Demand

OTHER

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

Interventions

Surgery PROCEDURE

lumpectomy or mastectomy with or without radiotherapy. Sentinel biopsy followed by axillary dissection (level I-II)

A: Surgical Therapy

Surgery on Demand PROCEDURE

if necessary local therapy on demand

B: Surgery on Demand

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Austrian Breast & Colorectal Cancer Study Group: lead
• Bayer: collaborator
• Amgen: collaborator
• Hoffmann-La Roche: collaborator
• AstraZeneca: collaborator
• Sanofi: collaborator
• Wyeth-Lederle Pharma GmbH: collaborator
• GlaxoSmithKline: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Fond of the Viennese Mayor: collaborator

Study Sites (14)

Hospital Guessing

Güssing, Burgenland, 7540, Austria

Location

Hospital Oberpullendorf

Oberpullendorf, Burgenland, 7350, Austria

Location

Ordination Dr. Wette

Saint Veit A. D. Glan, Carinthia, 9300, Austria

Location

Gynaegological Medical University Graz

Graz, Styria, 8036, Austria

Location

Medical University Graz, Oncology

Graz, Styria, 8036, Austria

Location

Medical University of Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Ordensklinikum Linz GmbH - BHS Linz, Coop. Study Group

Linz, Upper Austria, 4010, Austria

Location

Ordensklinikum Linz GmbH - Elisabethinen Linz

Linz, Upper Austria, 4010, Austria

Location

General Hospital Linz

Linz, Upper Austria, 4020, Austria

Location

Klinikum Wels-Grieskirchen GmbH

Wels, Upper Austria, 4600, Austria

Location

State Hospital Feldkirch

Feldkirch, Vorarlberg, 6807, Austria

Location

Paracelsus Medical University Salzburg-Oncology, Coop. Group

Salzburg, 5020, Austria

Location

Medical University of Vienna-General Hospital Vienna

Vienna, 1090, Austria

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

Related Publications (31)

• Babiera GV, Rao R, Feng L, Meric-Bernstam F, Kuerer HM, Singletary SE, Hunt KK, Ross MI, Gwyn KM, Feig BW, Ames FC, Hortobagyi GN. Effect of primary tumor extirpation in breast cancer patients who present with stage IV disease and an intact primary tumor. Ann Surg Oncol. 2006 Jun;13(6):776-82. doi: 10.1245/ASO.2006.03.033. Epub 2006 Apr 17.

  PMID: 16614878 BACKGROUND

• Blanchard DK, Bhatia P, Hilsenbeck SG, Elledge RM. Does surgical management of stage IV breast cancer effect outcome? SABCC 2006, San Antonio

  BACKGROUND

• Carmichael AR, Anderson ED, Chetty U, Dixon JM. Does local surgery have a role in the management of stage IV breast cancer? Eur J Surg Oncol. 2003 Feb;29(1):17-9. doi: 10.1053/ejso.2002.1339.

  PMID: 12559070 BACKGROUND

• Khan SA, Stewart AK, Morrow M. Does aggressive local therapy improve survival in metastatic breast cancer? Surgery. 2002 Oct;132(4):620-6; discussion 626-7. doi: 10.1067/msy.2002.127544.

  PMID: 12407345 BACKGROUND

• Rapiti E, Verkooijen HM, Vlastos G, Fioretta G, Neyroud-Caspar I, Sappino AP, Chappuis PO, Bouchardy C. Complete excision of primary breast tumor improves survival of patients with metastatic breast cancer at diagnosis. J Clin Oncol. 2006 Jun 20;24(18):2743-9. doi: 10.1200/JCO.2005.04.2226. Epub 2006 May 15.

  PMID: 16702580 BACKGROUND

• Gnerlich J, Jeffe DB, Deshpande AD, Beers C, Zander C, Margenthaler JA. Surgical removal of the primary tumor increases overall survival in patients with metastatic breast cancer: analysis of the 1988-2003 SEER data. Ann Surg Oncol. 2007 Aug;14(8):2187-94. doi: 10.1245/s10434-007-9438-0. Epub 2007 May 24.

  PMID: 17522944 BACKGROUND

• Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002 Oct 17;347(16):1233-41. doi: 10.1056/NEJMoa022152.

  PMID: 12393820 BACKGROUND

• Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002 Oct 17;347(16):1227-32. doi: 10.1056/NEJMoa020989.

  PMID: 12393819 BACKGROUND

• Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y; Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 Dec 17;366(9503):2087-106. doi: 10.1016/S0140-6736(05)67887-7.

  PMID: 16360786 BACKGROUND

• Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR Jr, Munshi N, Crawford ED. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001 Dec 6;345(23):1655-9. doi: 10.1056/NEJMoa003013.

  PMID: 11759643 BACKGROUND

• Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R; European Organisation for Research and Treatment of Cancer (EORTC) Genitourinary Group. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001 Sep 22;358(9286):966-70. doi: 10.1016/s0140-6736(01)06103-7.

  PMID: 11583750 BACKGROUND

• Norton L, Massague J. Is cancer a disease of self-seeding? Nat Med. 2006 Aug;12(8):875-8. doi: 10.1038/nm0806-875. No abstract available.

  PMID: 16892025 BACKGROUND

• Al-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells. Oncogene. 2004 Sep 20;23(43):7274-82. doi: 10.1038/sj.onc.1207947.

  PMID: 15378087 BACKGROUND

• Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006 Dec 7;444(7120):756-60. doi: 10.1038/nature05236. Epub 2006 Oct 18.

  PMID: 17051156 BACKGROUND

• Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8. doi: 10.1073/pnas.0530291100. Epub 2003 Mar 10.

  PMID: 12629218 BACKGROUND

• Kong FM, Anscher MS, Murase T, Abbott BD, Iglehart JD, Jirtle RL. Elevated plasma transforming growth factor-beta 1 levels in breast cancer patients decrease after surgical removal of the tumor. Ann Surg. 1995 Aug;222(2):155-62. doi: 10.1097/00000658-199508000-00007.

  PMID: 7543740 BACKGROUND

• Tang B, Vu M, Booker T, Santner SJ, Miller FR, Anver MR, Wakefield LM. TGF-beta switches from tumor suppressor to prometastatic factor in a model of breast cancer progression. J Clin Invest. 2003 Oct;112(7):1116-24. doi: 10.1172/JCI18899.

  PMID: 14523048 BACKGROUND

• Yang YA, Dukhanina O, Tang B, Mamura M, Letterio JJ, MacGregor J, Patel SC, Khozin S, Liu ZY, Green J, Anver MR, Merlino G, Wakefield LM. Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. J Clin Invest. 2002 Jun;109(12):1607-15. doi: 10.1172/JCI15333.

  PMID: 12070308 BACKGROUND

• Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 1993 Apr 29;362(6423):841-4. doi: 10.1038/362841a0.

  PMID: 7683111 BACKGROUND

• Linderholm B, Grankvist K, Wilking N, Johansson M, Tavelin B, Henriksson R. Correlation of vascular endothelial growth factor content with recurrences, survival, and first relapse site in primary node-positive breast carcinoma after adjuvant treatment. J Clin Oncol. 2000 Apr;18(7):1423-31. doi: 10.1200/JCO.2000.18.7.1423.

  PMID: 10735889 BACKGROUND

• Linderholm BK, Lindh B, Beckman L, Erlanson M, Edin K, Travelin B, Bergh J, Grankvist K, Henriksson R. Prognostic correlation of basic fibroblast growth factor and vascular endothelial growth factor in 1307 primary breast cancers. Clin Breast Cancer. 2003 Dec;4(5):340-7. doi: 10.3816/cbc.2003.n.039.

  PMID: 14715109 BACKGROUND

• Nishimura R, Nagao K, Miyayama H, Matsuda M, Baba K, Yamashita H, Fukuda M. Higher plasma vascular endothelial growth factor levels correlate with menopause, overexpression of p53, and recurrence of breast cancer. Breast Cancer. 2003;10(2):120-8. doi: 10.1007/BF02967636.

  PMID: 12736564 BACKGROUND

• Wu Y, Saldana L, Chillar R, Vadgama JV. Plasma vascular endothelial growth factor is useful in assessing progression of breast cancer post surgery and during adjuvant treatment. Int J Oncol. 2002 Mar;20(3):509-16.

  PMID: 11836562 BACKGROUND

• Kummel S, Eggemann H, Luftner D, Thomas A, Jeschke S, Zerfel N, Heilmann V, Emons G, Zeiser T, Ulm K, Kobl M, Korlach S, Schmid P, Sehouli J, Elling D, Blohmer JU. Changes in the circulating plasma levels of VEGF and VEGF-D after adjuvant chemotherapy in patients with breast cancer and 1 to 3 positive lymph nodes. Anticancer Res. 2006 Mar-Apr;26(2C):1719-26.

  PMID: 16617567 BACKGROUND

• Caine GJ, Stonelake PS, Lip GY, Blann AD. Changes in plasma vascular endothelial growth factor, angiopoietins, and their receptors following surgery for breast cancer. Cancer Lett. 2007 Apr 8;248(1):131-6. doi: 10.1016/j.canlet.2006.06.011. Epub 2006 Aug 7.

  PMID: 16891056 BACKGROUND

• Curigliano G, Petit JY, Bertolini F, Colleoni M, Peruzzotti G, de Braud F, Gandini S, Giraldo A, Martella S, Orlando L, Munzone E, Pietri E, Luini A, Goldhirsch A. Systemic effects of surgery: quantitative analysis of circulating basic fibroblast growth factor (bFGF), Vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) in patients with breast cancer who underwent limited or extended surgery. Breast Cancer Res Treat. 2005 Sep;93(1):35-40. doi: 10.1007/s10549-005-3381-1.

  PMID: 16184456 BACKGROUND

• Joffe JK, Banks RE, Forbes MA, Hallam S, Jenkins A, Patel PM, Hall GD, Velikova G, Adams J, Crossley A, Johnson PW, Whicher JT, Selby PJ. A phase II study of interferon-alpha, interleukin-2 and 5-fluorouracil in advanced renal carcinoma: clinical data and laboratory evidence of protease activation. Br J Urol. 1996 May;77(5):638-49. doi: 10.1046/j.1464-410x.1996.09573.x.

  PMID: 8689103 BACKGROUND

• Wagner JR, Walther MM, Linehan WM, White DE, Rosenberg SA, Yang JC. Interleukin-2 based immunotherapy for metastatic renal cell carcinoma with the kidney in place. J Urol. 1999 Jul;162(1):43-5. doi: 10.1097/00005392-199907000-00011.

  PMID: 10379736 BACKGROUND

• Fitzal F, Sporn EP, Draxler W, Mittlbock M, Taucher S, Rudas M, Riedl O, Helbich TH, Jakesz R, Gnant M. Preoperative core needle biopsy does not increase local recurrence rate in breast cancer patients. Breast Cancer Res Treat. 2006 May;97(1):9-15. doi: 10.1007/s10549-005-6935-3.

  PMID: 16502019 BACKGROUND

• El-Tamer MB, Ward BM, Schifftner T, Neumayer L, Khuri S, Henderson W. Morbidity and mortality following breast cancer surgery in women: national benchmarks for standards of care. Ann Surg. 2007 May;245(5):665-71. doi: 10.1097/01.sla.0000245833.48399.9a.

  PMID: 17457156 BACKGROUND

• Bjelic-Radisic V, Fitzal F, Knauer M, Steger G, Egle D, Greil R, Schrenk P, Balic M, Singer C, Exner R, Soelkner L, Gnant M; ABCSG. Primary surgery versus no surgery in synchronous metastatic breast cancer: patient-reported quality-of-life outcomes of the prospective randomized multicenter ABCSG-28 Posytive Trial. BMC Cancer. 2020 May 6;20(1):392. doi: 10.1186/s12885-020-06894-2.

  PMID: 32375735 DERIVED

MeSH Terms

Conditions

Neoplastic Cells, Circulating; Breast Neoplasms

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Trial Office Director
• Organization: ABCSG (Austrian Breast & Colorectal Cancer Study Group)

info@abcsg.at

+43 1 4089230

Study Officials

• Florian Fitzal, MD

  Austrian Breast & Colorectal Cancer Study Group

  STUDY DIRECTOR

• Michael Gnant, MD

  Austrian Breast & Colorectal Cancer Study Group

  STUDY DIRECTOR

• Guenther Steger, MD

  Austrian Breast & Colorectal Cancer Study Group

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2009
• First Posted: November 18, 2009
• Study Start: November 24, 2010
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2022
• Last Updated: August 19, 2024
• Results First Posted: August 19, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (14)