Skip to main content
SpringerLink
Log in

New Insights on the Role of Surgery for the Breast Primary Tumor in Patients Presenting With Stage IV Disease

  • Local-Regional Evaluation and Therapy (EP Mamounas, Section Editor)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Though systemic therapy has been the standard treatment for patients with de novo metastatic breast cancer, a large number of retrospective studies demonstrate that resection of the primary tumor is associated with improved survival. Here, we review the potential rationale for resection, available retrospective and prospective data, and challenges in applying these data in clinical practice.

Recent Findings

Results from prospective trials to date are limited. The only published randomized controlled trial concluded that locoregional therapy for the primary tumor did not result in improved overall survival and was associated with shorter distant progression-free survival.

Summary

Recommendations regarding the potential survival advantage of locoregional therapy cannot be firmly made until additional results from prospective trials are available. Systemic therapy remains first-line treatment, and surgical resection of the primary tumor should only be considered for select patients after a full discussion of the limitations of the current data.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Howlader N, Ries LA, Stinchcomb DG, Edwards BK. The impact of underreported Veterans Affairs data on national cancer statistics: analysis using population-based SEER registries. J Natl Cancer Inst. 2009;101:533–6.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ly BH, Nguyen NP, Vinh-Hung V, et al. Loco-regional treatment in metastatic breast cancer patients: is there a survival benefit? Breast Cancer Res Treat. 2010;119:537–45.

    Article  PubMed  Google Scholar 

  3. Dawood S, Broglio K, Ensor J, et al. Survival differences among women with de novo stage IV and relapsed breast cancer. Ann Oncol. 2010;21:2169–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lobbezoo DJ, van Kampen RJ, Voogd AC, et al. Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer? Br J Cancer. 2015;112:1445–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Staren ED, Salerno C, Rongione A, et al. Pulmonary resection for metastatic breast cancer. Arch Surg. 1992;127:1282–4.

    Article  CAS  PubMed  Google Scholar 

  6. Meimarakis G, Ruttinger D, Stemmler J, et al. Prolonged overall survival after pulmonary metastasectomy in patients with breast cancer. Ann Thorac Surg. 2013;95:1170–80.

    Article  PubMed  Google Scholar 

  7. Adam R, Aloia T, Krissat J, et al. Is liver resection justified for patients with hepatic metastases from breast cancer? Ann Surg. 2006;244:897–907. discussion 907-898

    Article  PubMed  PubMed Central  Google Scholar 

  8. Friedel G, Pastorino U, Ginsberg RJ, et al. Results of lung metastasectomy from breast cancer: prognostic criteria on the basis of 467 cases of the International Registry of Lung Metastases. Eur J Cardiothorac Surg. 2002;22:335–44.

    Article  PubMed  Google Scholar 

  9. Friedel G, Linder A, Toomes H. The significance of prognostic factors for the resection of pulmonary metastases of breast cancer. Thorac Cardiovasc Surg. 1994;42:71–5.

    Article  CAS  PubMed  Google Scholar 

  10. Milano MT, Katz AW, Zhang H, Okunieff P. Oligometastases treated with stereotactic body radiotherapy: long-term follow-up of prospective study. Int J Radiat Oncol Biol Phys. 2012;83:878–86.

    Article  PubMed  Google Scholar 

  11. Milano MT, Zhang H, Metcalfe SK, et al. Oligometastatic breast cancer treated with curative-intent stereotactic body radiation therapy. Breast Cancer Res Treat. 2009;115:601–8.

    Article  PubMed  Google Scholar 

  12. Kobayashi T, Ichiba T, Sakuyama T, et al. Possible clinical cure of metastatic breast cancer: lessons from our 30-year experience with oligometastatic breast cancer patients and literature review. Breast Cancer. 2012;19:218–37.

    Article  PubMed  Google Scholar 

  13. Pockaj BA, Wasif N, Dueck AC, et al. Metastasectomy and surgical resection of the primary tumor in patients with stage IV breast cancer: time for a second look? Ann Surg Oncol. 2010;17:2419–26.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Standard of care therapy with or without stereotactic radiosurgery and/or surgery in treating patients with limited metastatic breast cancer. https://clinicaltrials.gov/ct2/show/NCT02364557.

  15. Mickisch GH, Garin A, van Poppel H, et al. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001;358:966–70.

    Article  CAS  PubMed  Google Scholar 

  16. 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  PubMed  Google Scholar 

  17. 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. discussion 534-535

    Article  CAS  PubMed  Google Scholar 

  18. Hallissey MT, Allum WH, Roginski C, Fielding JW. Palliative surgery for gastric cancer. Cancer. 1988;62:440–4.

    Article  CAS  PubMed  Google Scholar 

  19. Essner R, Lee JH, Wanek LA, et al. Contemporary surgical treatment of advanced-stage melanoma. Arch Surg. 2004;139:961–6. discussion 966-967

    Article  PubMed  Google Scholar 

  20. Fehm T, Sagalowsky A, Clifford E, et al. Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant. Clin Cancer Res. 2002;8:2073–84.

    CAS  PubMed  Google Scholar 

  21. Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–91.

    Article  CAS  PubMed  Google Scholar 

  22. Budd GT, Cristofanilli M, Ellis MJ, et al. Circulating tumor cells versus imaging—predicting overall survival in metastatic breast cancer. Clin Cancer Res. 2006;12:6403–9.

    Article  CAS  PubMed  Google Scholar 

  23. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–84.

    Article  CAS  PubMed  Google Scholar 

  24. Li X, Lewis MT, Huang J, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100:672–9.

    Article  CAS  PubMed  Google Scholar 

  25. Kakarala M, Wicha MS. Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol. 2008;26:2813–20.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Danna EA, Sinha P, Gilbert M, et al. Surgical removal of primary tumor reverses tumor-induced immunosuppression despite the presence of metastatic disease. Cancer Res. 2004;64:2205–11.

    Article  CAS  PubMed  Google Scholar 

  27. Prehn RT. Two competing influences that may explain concomitant tumor resistance. Cancer Res. 1993;53:3266–9.

    CAS  PubMed  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  PubMed  Google Scholar 

  29. Demicheli R, Retsky MW, Hrushesky WJ, et al. The effects of surgery on tumor growth: a century of investigations. Ann Oncol. 2008;19:1821–8.

    Article  CAS  PubMed  Google Scholar 

  30. Retsky M, Bonadonna G, Demicheli R, et al. Hypothesis: induced angiogenesis after surgery in premenopausal node-positive breast cancer patients is a major underlying reason why adjuvant chemotherapy works particularly well for those patients. Breast Cancer Res. 2004;6:R372–4.

    Article  PubMed  PubMed Central  Google Scholar 

  31. O'Reilly MS, Holmgren L, Shing Y, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 1994;79:315–28.

    Article  PubMed  Google Scholar 

  32. ten Kate M, Hofland LJ, van Grevenstein WM, et al. Influence of proinflammatory cytokines on the adhesion of human colon carcinoma cells to lung microvascular endothelium. Int J Cancer. 2004;112:943–50.

    Article  PubMed  Google Scholar 

  33. Benish M, Bartal I, Goldfarb Y, et al. Perioperative use of beta-blockers and COX-2 inhibitors may improve immune competence and reduce the risk of tumor metastasis. Ann Surg Oncol. 2008;15:2042–52.

    Article  PubMed  Google Scholar 

  34. 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  PubMed  Google Scholar 

  35. 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;115:7–12.

    Article  PubMed  Google Scholar 

  36. Blanchard DK, Shetty PB, Hilsenbeck SG, Elledge RM. Association of surgery with improved survival in stage IV breast cancer patients. Ann Surg. 2008;247:732–8.

    Article  PubMed  Google Scholar 

  37. Cady B, Nathan NR, Michaelson JS, et al. Matched pair analyses of stage IV breast cancer with or without resection of primary breast site. Ann Surg Oncol. 2008;15:3384–95.

    Article  CAS  PubMed  Google Scholar 

  38. Dominici L, Najita J, Hughes M, et al. Surgery of the primary tumor does not improve survival in stage IV breast cancer. Breast Cancer Res Treat. 2011;129:459–65.

    Article  PubMed  PubMed Central  Google Scholar 

  39. 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  PubMed  Google Scholar 

  40. Gnerlich J, Jeffe DB, Deshpande AD, et al. 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  PubMed  Google Scholar 

  41. 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  PubMed  Google Scholar 

  42. Khan SA, Stewart AK, Morrow M. Does aggressive local therapy improve survival in metastatic breast cancer? Surgery. 2002;132:620–6. discussion 626-627

    Article  PubMed  Google Scholar 

  43. Le Scodan R, Stevens D, Brain E, et al. Breast cancer with synchronous metastases: survival impact of exclusive locoregional radiotherapy. J Clin Oncol. 2009;27:1375–81.

    Article  PubMed  Google Scholar 

  44. Leung AM, Vu HN, Nguyen KA, et al. Effects of surgical excision on survival of patients with stage IV breast cancer. J Surg Res. 2010;161:83–8.

    Article  PubMed  Google Scholar 

  45. Neuman HB, Morrogh M, Gonen M, et al. Stage IV breast cancer in the era of targeted therapy: does surgery of the primary tumor matter? Cancer. 2010;116:1226–33.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Pathy NB, Verkooijen HM, Taib NA, et al. Impact of breast surgery on survival in women presenting with metastatic breast cancer. Br J Surg. 2011;98:1566–72.

    Article  PubMed  Google Scholar 

  47. Perez-Fidalgo JA, Pimentel P, Caballero A, et al. Removal of primary tumor improves survival in metastatic breast cancer. Does timing of surgery influence outcomes? Breast. 2011;20:548–54.

    Article  PubMed  Google Scholar 

  48. Rao R, Feng L, Kuerer HM, et al. Timing of surgical intervention for the intact primary in stage IV breast cancer patients. Ann Surg Oncol. 2008;15:1696–702.

    Article  PubMed  Google Scholar 

  49. 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  PubMed  Google Scholar 

  50. Rashaan ZM, Bastiaannet E, Portielje JE, et al. Surgery in metastatic breast cancer: patients with a favorable profile seem to have the most benefit from surgery. Eur J Surg Oncol. 2012;38:52–6.

    Article  CAS  PubMed  Google Scholar 

  51. 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  PubMed  Google Scholar 

  52. Shien T, Kinoshita T, Shimizu 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 

  53. Muzaffar M, Kachare S, Vohra N. Impact of primary tumor surgery in stage IV male breast cancer. Clin Breast Cancer 2016 [Epub ahead of print]. doi: 10.1016/j.clbc.2016.11.001.

  54. AlJohani B, AlMalik O, Anwar E, et al. Impact of surgery on survival in stage IV breast cancer. Breast J. 2016;22:678–82.

    Article  PubMed  Google Scholar 

  55. Warschkow R, Guller U, Tarantino I, et al. Improved survival after primary tumor surgery in metastatic breast cancer: a propensity-adjusted, population-based SEER trend analysis. Ann Surg. 2016;263:1188–98.

    Article  PubMed  Google Scholar 

  56. Harano K, Lei X, Gonzalez-Angulo AM, et al. Clinicopathological and surgical factors associated with long-term survival in patients with HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2016;159:367–74.

    Article  CAS  PubMed  Google Scholar 

  57. Thomas A, Khan SA, Chrischilles EA, Schroeder MC. Initial surgery and survival in stage IV breast cancer in the United States, 1988-2011. JAMA Surg. 2016;151:424–31.

    Article  PubMed  Google Scholar 

  58. Quinn EM, Kealy R, O'Meara S, et al. Is there a role for locoregional surgery in stage IV breast cancer? Breast. 2015;24:32–7.

    Article  PubMed  Google Scholar 

  59. van de Water W, Bastiaannet E, Egan KM, et al. Management of primary metastatic breast cancer in elderly patients—an international comparison of oncogeriatric versus standard care. J Geriatr Oncol. 2014;5:252–9.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Samiee S, Berardi P, Bouganim N, et al. Excision of the primary tumour in patients with metastatic breast cancer: a clinical dilemma. Curr Oncol. 2012;19:e270–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. McGuire KP, Eisen S, Rodriguez A, et al. Factors associated with improved outcome after surgery in metastatic breast cancer patients. Am J Surg. 2009;198:511–5.

    Article  PubMed  Google Scholar 

  62. Nguyen DH, Truong PT, Alexander C, et al. Can locoregional treatment of the primary tumor improve outcomes for women with stage IV breast cancer at diagnosis? Int J Radiat Oncol Biol Phys. 2012;84:39–45.

    Article  PubMed  Google Scholar 

  63. Lang JE, Tereffe W, Mitchell MP, et al. Primary tumor extirpation in breast cancer patients who present with stage IV disease is associated with improved survival. Ann Surg Oncol. 2013;20:1893–9.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Briasoulis E, Karavasilis V, Kostadima L, et al. Metastatic breast carcinoma confined to bone: portrait of a clinical entity. Cancer. 2004;101:1524–8.

    Article  PubMed  Google Scholar 

  65. Sherry MM, Greco FA, Johnson DH, Hainsworth JD. Metastatic breast cancer confined to the skeletal system. An indolent disease. Am J Med. 1986;81:381–6.

    Article  CAS  PubMed  Google Scholar 

  66. • Badwe R, Hawaldar R, Nair N, et al. 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. This is the first published randomized controlled trial evaluating the survival benefit of locoregional therapy for the primary tumor in patients with de novo metastatic breast cancer. Locoregional therapy for the primary tumor did not result in improved overall survival and was associated with shorter distant progression-free survival.

    Article  PubMed  Google Scholar 

  67. • Soran A, Ozmen V, Ozbas S et al A randomized controlled trial evaluating resection of the primary breast tumor in women presenting with de novo stage IV breast cancer: Turkish study (protocol MF07-01). J Clin Oncol 2016;34(suppl):abstr 1005. The unpublished results of this multicenter randomized trial demonstrated a survival benefit associated with local therapy for the primary tumor at a median of 40 months follow-up. The surgery group, however, may have been weighted towards more favorable disease characteristics.

  68. Soran A, Ozmen V, Ozbas S et al Early follow up of a randomized trial evaluating resection of the primary breast tumor in women presenting with de novo stage IV breast cancer; Turkish study (protocol MF07-01). Cancer Res 2013;73(24 Suppl):Abstract nr S2–03.

  69. • 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;34(suppl):abstr 1006. This multicenter prospective registry trial evaluating the role of surgery for the primary tumor in de novo stage IV disease demonstrated that surgery did not impact overall survival among patients with an intact primary who responded to first-line systemic therapy.

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Brigham and Women’s Hospital, Boston, MA, USA

    Anvy Nguyen & Tari A. King

  2. Surgical Oncology, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, USA

    Anvy Nguyen & Tari A. King

Authors
  1. Anvy Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tari A. King
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tari A. King.

Ethics declarations

Conflict of Interest

Anvy Nguyen and Tari A. King declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Local-Regional Evaluation and Therapy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nguyen, A., King, T.A. New Insights on the Role of Surgery for the Breast Primary Tumor in Patients Presenting With Stage IV Disease. Curr Breast Cancer Rep 9, 137–147 (2017). https://doi.org/10.1007/s12609-017-0241-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12609-017-0241-z

Keywords

Search

Navigation