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Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients.

Methods

At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor.

Results

The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group. Hazard of death was 34% lower in the LRT group than in the ST group (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.49–0.88; p = 0.005). Unplanned subgroup analyses showed that the risk of death was statistically lower in the LRT group than in the ST group with respect to estrogen receptor (ER)/progesterone receptor (PR)(+) (HR 0.64; 95% CI 0.46–0.91; p = 0.01), human epidermal growth factor 2 (HER2)/neu(–) (HR 0.64; 95% CI 0.45–0.91; p = 0.01), patients younger than 55 years (HR 0.57; 95% CI 0.38–0.86; p = 0.007), and patients with solitary bone-only metastases (HR 0.47; 95% CI 0.23–0.98; p = 0.04).

Conclusion

In the current trial, improvement in 36-month survival was not observed with upfront surgery for stage IV breast cancer patients. However, a longer follow-up study (median, 40 months) showed statistically significant improvement in median survival. When locoregional treatment in de novo stage IV BC is discussed with the patient as an option, practitioners must consider age, performance status, comorbidities, tumor type, and metastatic disease burden.

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References

  1. Carmichael AR, Anderson EDC, Chetty U, Dixon JM. Does local surgery have a role in the management of stage IV breast cancer? Eur J Surg Oncol. 2003;29:17–9.

    Article  CAS  Google Scholar 

  2. 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;14:2187–94.

    Article  Google Scholar 

  3. Blanchard DK, Bhatia P, Hilsenbeck SG, Elledge RM. Does surgical management of stage IV breast cancer affect outcome?. Breast Cancer Res Treat. 2006; 2006(Suppl 1):100:18

    Google Scholar 

  4. Hortobagyi GN. Treatment of breast cancer. N Eng J Med. 1998;339:974–84.

    Article  CAS  Google Scholar 

  5. Giordano SH, Buzdar AU, Smith TL, et al. Is breast cancer survival improving? Cancer. 2004;100:44–52.

    Article  Google Scholar 

  6. Andre F, Slimane K, Bachelot T, et al. Breast cancer with synchronous metastases: trends in survival during a 14-year period. J Clin Oncol. 2004;22:3302–8.

    Article  Google Scholar 

  7. Essner R, Lee JH, Wanek LA, et al. Contemporary surgical treatment of advanced-stage melanoma. Arch Surg. 2004;139:961–6.

    Article  Google Scholar 

  8. Flanigan RC, Salmon SE, Blumenstein BA, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001;345:1655–9.

    Article  CAS  Google Scholar 

  9. Rosen SA, Buell JF, Yoshida A, et al. Initial presentation with stage IV colorectal cancer: how aggressive should we be? Arch Surg. 2000;135:530–4.

    Article  CAS  Google Scholar 

  10. Hallissey MT, Allum WH, Roginski C, et al. Palliative surgery for gastric cancer. Cancer. 1988;62:440–4.

    Article  CAS  Google Scholar 

  11. Danna EA, Sinha P, Gilbert M, Clements UK, Pulaski BA, Ostrand-Rosenberg S. Surgical removal of primary tumor reverses tumor-induced immunosuppression despite the presence of metastatic disease. Cancer Res. 2004; 64:2205–11.

    Article  CAS  Google Scholar 

  12. Norton L, Massague J, et al. Is cancer a disease of self-seeding? Nat Med. 2006;12:875–8.

    Article  CAS  Google Scholar 

  13. Khan SA, Stewart AK, Morrow M. Does aggressive local therapy improve survival in metastatic breast cancer? Surgery. 2002;132:620–7.

    Article  Google Scholar 

  14. Khan SA. Primary tumor resection in stage IV breast cancer: consistent benefit, or consistent bias? Ann Surg Oncol. 2007;14:3285–7.

    Article  Google Scholar 

  15. Babiera GV, Rao R, Feng L, et al. Effect of primary tumor extirpation in breast cancer patients who present with stage IV disease and an intact primary tumor. Ann Surg Oncol. 2006;13:776–82.

    Article  Google Scholar 

  16. Rapiti E, Verkooijen HM, Vlastos G, et al. Complete excision of primary breast tumor improves survival of patients with metastatic breast cancer at diagnosis. J Clin Oncol. 2006;24:2743–9.

    Article  Google Scholar 

  17. Fields RC, Jeffe DB, Trinkaus K, et al. Surgical resection of the primary tumor is associated with increased long-term survival in patients with stage IV breast cancer after controlling for site of metastasis. Ann Surg Oncol. 2007;14:3345–51.

    Article  Google Scholar 

  18. Arriagada R, Rutqvist LE, Mattsson A, et al. Adequate locoregional treatment for early breast cancer may prevent secondary dissemination. J Clin Oncol. 1995;13:2869–78.

    Article  CAS  Google Scholar 

  19. Hazard HW, Gorla SR, Scholtens D, et al. Surgical resection of the primary tumor, chest wall control, and survival in women with metastatic breast cancer. Cancer. 2008;113:2011–9.

    Article  Google Scholar 

  20. Nieto Y, Nawaz S, Jones RB, et al. Prognostic model for relapse after high-dose chemotherapy with autologous stem-cell transplantation for stage IV oligometastatic breast cancer. J Clin Oncol. 2002;20:707–18.

    Article  CAS  Google Scholar 

  21. Bafford AC, Burstein HJ, Barkley CR, et al. Breast surgery in stage IV breast cancer: impact of staging and patient selection on overall survival. Breast Cancer Res Treat. 2009;115:7.

    Article  Google Scholar 

  22. Ruiterkamp J, Ernst MF, van de Poll-Franse LV, et al. Surgical resection of the primary tumour is associated with improved survival in patients with distant metastatic breast cancer at diagnosis. Eur J Surg Oncol. 2009;35:1146–51.

    Article  CAS  Google Scholar 

  23. Shien T, Kionoshita T, Shimzu C, et al. Primary tumor resection improves the survival of younger patients with metastatic breast cancer. Oncol Rep. 2009;21:827–32.

    PubMed  Google Scholar 

  24. Harris E, Barry M, Kell MR. Meta-analysis to determine if surgical resection of the primary tumour in the setting of stage IV breast cancer impacts on survival. Ann Surg Oncol. 2013;20:2828–34.

    Article  Google Scholar 

  25. Petrelli F, Barni S. Surgery of primary tumors in stage 4 breast cancer: an updated meta-analysis of published studies with meta-regression. Med Oncol. 2012;29:3282–90.

    Article  Google Scholar 

  26. Khan SA. Surgical management of de novo stage 4 breast cancer. Semin Radiat Oncol. 2016;26:79–86.

    Article  Google Scholar 

  27. Baum M, Demicheli R, Hrushesky W, et al. Does surgery unfavourably perturb the ‘‘natural history’’ of early breast cancer by accelerating the appearance of distant metastases? Eur J Cancer. 2005;41:508–15.

    Article  Google Scholar 

  28. Coffey JC, Wang JH, Smith MJ, et al. Excisional surgery for cancer cure: therapy at a cost. Lancet Oncol. 2003;4:760–8.

    Article  CAS  Google Scholar 

  29. Demicheli R, Valagussa P, Bonadonna G. Does surgery modify growth kinetics of breast cancer micrometastases? Br J Cancer. 2001;85:490–2.

    Article  CAS  Google Scholar 

  30. Soran A, Ozbas S, Kelsey SF, Gulluoglu BM. Randomized trial comparing locoregional resection of primary tumor with no surgery in stage IV breast cancer at the presentation (Protocol MF07-01): a study of Turkish Federation of the National Societies for Breast Disease. Breast J. 2009;15:399–403.

    Article  Google Scholar 

  31. Kernan WN, Viscoli CM, Makuch RW, Brass LM, Horwitz RI. Stratified randomization for clinical trials. J Clin Epidemiol. 1999;52:19–26.

    Article  CAS  Google Scholar 

  32. Badwe R, Hawaldar R, Nair N, Kaushik R, Parmar V, Siddique S, Budrukkar A, Mittra I, Gupta S. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol. 2015;16:1380–8.

    Article  Google Scholar 

  33. King TA, Lyman J, Gonen M, et al. A prospective analysis of surgery and survival in stage IV breast cancer (TBCRC 013). J Clin Oncol. 2016. https://doi.org/10.1200/JCO.2016.34.15_suppl.1006

    Article  PubMed  PubMed Central  Google Scholar 

  34. Neuman HB, Morrogh M, Gonen M, Van Zee KJ, Morrow M, King TA. Stage IV breast cancer in the era of targeted therapy: does surgery of the primary tumor matter? Cancer. 2010;116:1226–33

    Article  Google Scholar 

  35. Ceylan B, Ozerdogan N. Factors affecting age of onset of menopause and determination of quality of life in menopause. J Turk Soc Obstet Gynecol. 2015;1:43–9.

    Article  Google Scholar 

  36. Mendoza ESR, Moreno E, Caguioa PB. Predictors of early distant metastasis in women with breast cancer. J Cancer Res Clin Oncol. 2013;139:645–52.

    Article  Google Scholar 

  37. Retsky M, Demicheli R, Hrushesky W. Premenopausal status accelerates relapse in node positive breast cancer: hypothesis links angiogenesis, screening controversy. Breast Cancer Res Treat. 2001;65:217–24.

    Article  CAS  Google Scholar 

  38. Nguyen DH, Truong PT, Walter CV, Hayashi E, Christie JL, Alexander C. Limited M1 disease: a significant prognostic factor for stage IV breast cancer. Ann Surg Oncol. 2012;19:3028–34.

    Article  Google Scholar 

  39. NCCN guidelines version 2.2016. Invasive breast cancer. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf

  40. André F, Bachelot T, Commo F, et al. Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER). Lancet Oncol. 2014;15:267–74.

    Article  Google Scholar 

  41. Amir E, Miller N, Geddie W, et al. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol. 2012;30:587–92.

    Article  Google Scholar 

  42. Balci TA, Koc ZP, Komek H. Bone scan or (18)F-fluorodeoxyglucose positron emission tomography/computed tomography: which modality better shows bone metastases of breast cancer? Breast Care Basel. 2012;7:389–93.

    PubMed  PubMed Central  Google Scholar 

  43. Caglar M, Kupik O, Karabulut E, Høilund-Carlsen PF. Detection of bone metastases in breast cancer patients in the PET/CT era: do we still need the bone scan? Rev Esp Med Nucl Imagen Mol. 2016;35:3–11.

    CAS  PubMed  Google Scholar 

  44. Niikura N, Hashimoto J, Kazama T, et al. Diagnostic performance of (18)F-fluorodeoxyglucose PET/CT and bone scintigraphy in breast cancer patients with suspected bone metastasis. Breast Cancer. 2016;23:662–7.

    Article  Google Scholar 

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Acknowledgments

We thank Christine Heiner, Scientific Writer, and Jeffrey Sutton, MD, for their assistance with language editing, as well as Drs. Sheryl F. Kelsey and Elizabeth D. Kennard for their statistical overview from The University of Pittsburgh and Temel Dagoglu, MD from Istanbul University for patient recruitment. In memory of Barry Lembersky, MD, of the University of Pittsburgh for his guidance and execution of the study. This study is registered on clinicaltrials.gov with identifier number NCT00557986.

Funding

Funding was provided by Turkish Federation of Breast Disease Societies (Grant Number MF07-01).

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Correspondence to Atilla Soran MD, MPH, FNCBC, FACS.

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Soran, A., Ozmen, V., Ozbas, S. et al. Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01. Ann Surg Oncol 25, 3141–3149 (2018). https://doi.org/10.1245/s10434-018-6494-6

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  • DOI: https://doi.org/10.1245/s10434-018-6494-6

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