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Surgery in the Setting of Metastatic Breast Cancer

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Abstract

Purpose of Review

Among individuals with metastatic breast cancer, surgical resection of the primary tumor remains controversial, and its benefit is unclear. In this review, we highlight select retrospective and prospective studies which have sought to address this clinical scenario. In addition, we discuss further considerations that may be relevant.

Recent Findings

Numerous retrospective studies have suggested a potential survival benefit associated with surgical resection of the primary breast tumor in women with metastatic disease; however, three randomized controlled trials more recently have challenged these findings. Mixed results have demonstrated no survival benefit with locoregional treatment versus limited benefit in select patient groups.

Summary

Prospective studies suggest that most patients with metastatic breast cancer are unlikely to experience a survival benefit related to resection of their primary tumor. However, ongoing work seeks to further define if there may be select subgroups that could benefit from surgery.

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References

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

  1. American Cancer Society: breast cancer facts & figures 2019-2020. American Cancer Society. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2019-2020.pdf. Published 2019. Accessed 10/30/2019.

  2. Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271–7.

    Article  PubMed  Google Scholar 

  3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.

    Article  PubMed  Google Scholar 

  4. Tao L, Chu L, Wang LI, et al. Occurrence and outcome of de novo metastatic breast cancer by subtype in a large, diverse population. Cancer Causes Control. 2016;27(9):1127–38.

    Article  PubMed  Google Scholar 

  5. Mariotto AB, Etzioni R, Hurlbert M, Penberthy L, Mayer M. Estimation of the number of women living with metastatic breast cancer in the United States. Cancer Epidemiol Biomarkers Prev. 2017;26(6):809–15.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Caswell-Jin JL, Plevritis SK, Tian L, et al. Change in survival in metastatic breast cancer with treatment advances: meta-analysis and systematic review. JNCI cancer spectrum. 2018;2(4):pky062.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sundquist M, Brudin L, Tejler G. Improved survival in metastatic breast cancer 1985-2016. Breast. 2017;31:46–50.

    Article  PubMed  Google Scholar 

  8. Thomas A, Khan SA, Chrischilles EA, Schroeder MC. Initial surgery and survival in stage IV breast cancer in the United States, 1988-2011. JAMA surgery. 2016;151(5):424–31.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Taskindoust M, Thomas SM, Sammons SL, et al. Survival outcomes among patients with metastatic breast cancer: review of 47,000 patients. Ann Surg Oncol. 2021;28(12):7441–9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ogiya R, Sagara Y, Niikura N, Freedman RA. Impact of subtype on survival of young patients with stage IV breast cancer. Clin Breast Cancer. 2019;19(3):200–207.e201.

    Article  PubMed  Google Scholar 

  11. Malmgren JA, Calip GS, Atwood MK, Mayer M, Kaplan HG. Metastatic breast cancer survival improvement restricted by regional disparity: surveillance, epidemiology, and end results and institutional analysis: 1990 to 2011. Cancer. 2020;126(2):390–9.

    Article  CAS  PubMed  Google Scholar 

  12. Di Meglio A, Freedman RA, Lin NU, et al. Time trends in incidence rates and survival of newly diagnosed stage IV breast cancer by tumor histology: a population-based analysis. Breast cancer research and treatment. 2016;157(3):587–96.

    Article  PubMed  Google Scholar 

  13. Howlader N, Cronin KA, Kurian AW, Andridge R. Differences in breast cancer survival by molecular subtypes in the United States. Cancer Epidemiol Biomarkers Prev. 2018;27(6):619–26.

    Article  CAS  PubMed  Google Scholar 

  14. Smith CEP, Marcom PK, Mitri ZI. Real-word incidence and management of durable complete response in de novo metastatic HER2-positive breast cancer. Journal of Clinical Oncology. 2020;38(15_suppl):e13017–7.

    Article  Google Scholar 

  15. Leone BA, Vallejo CT, Romero AO, et al. Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis. Breast Cancer Res Treat. 2017;161(3):537–48.

    Article  CAS  PubMed  Google Scholar 

  16. • Plichta JK, Thomas SM, Sergesketter AR, et al. A novel staging system for de novo metastatic breast cancer refines prognostic estimates. Ann Surg. 2020;275(4):784–92 This work suggests that the improved survival outcomes for patients with de novo metastatic breast cancer should likely be considered when assigning a stage classification, and future studies should evaluate if this subgrouping may be useful for treatment decision making, such as determing who may benefit from surgery.

    Article  Google Scholar 

  17. Moussavi-Harami SF, Wisinski KB, Beebe DJ. Circulating tumor cells in metastatic breast cancer: a prognostic and predictive marker. J Patient Cent Res Rev. 2014;1(2):85–92.

    Article  PubMed  Google Scholar 

  18. Carter P, Alifrangis C, Cereser B, et al. Molecular profiling of advanced breast cancer tumors is beneficial in assisting clinical treatment plans. Oncotarget. 2018;9(25):17589–96.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ross JS, Gay LM. Comprehensive genomic sequencing and the molecular profiles of clinically advanced breast cancer. Pathology. 2017;49(2):120–32.

    Article  CAS  PubMed  Google Scholar 

  20. Santa-Maria CA, Kruse M, Raska P, et al. Impact of tissue-based genomic profiling on clinical decision making in the management of patients with metastatic breast cancer at academic centers. Breast Cancer Res Treat. 2017;166(1):179–84.

    Article  CAS  PubMed  Google Scholar 

  21. Gradishar WJ, Anderson BO, Abraham J, et al. Breast cancer, version 3.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2020;18(4):452–78.

    Article  CAS  PubMed  Google Scholar 

  22. Khan SA, Stewart AK, Morrow M. Does aggressive local therapy improve survival in metastatic breast cancer? Surgery. 2002;132(4):620–6 discussion 626-627.

    Article  PubMed  Google Scholar 

  23. 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(6):1696–702.

    Article  PubMed  Google Scholar 

  24. Lane WO, Thomas SM, Blitzblau RC, et al. Surgical resection of the primary tumor in women with de novo stage IV breast cancer: contemporary practice patterns and survival analysis. Ann Surg. 2019;269(3):537–44.

    Article  PubMed  Google Scholar 

  25. Dominici L, Najita J, Hughes M, et al. Surgery of the primary tumor does not improve survival in stage IV breast cancer. Breast cancer research and treatment. 2011;129(2):459–65.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Marks CE, Thomas SM, Fayanju OM, et al. Metastatic breast cancer: who benefits from surgery? Am J Surg. 2021;223(1):81–93.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 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 research and treatment. 2009;115(1):7–12.

    Article  PubMed  Google Scholar 

  28. 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. The LancetOncology. 2015;16(13):1380–8.

    Google Scholar 

  29. 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. 2018;25(11):3141–9.

    Article  PubMed  Google Scholar 

  30. Tosello G, Torloni MR, Mota BS, Neeman T, Riera R. Breast surgery for metastatic breast cancer. Cochrane Database Syst Rev. 2018;3(3):Cd011276.

    PubMed  Google Scholar 

  31. Khan SA, Zhao F, Solin LJ, et al. A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: a trial of the ECOG-ACRIN Research Group (E2108). J Clin Oncol. 2020;38(18_suppl):LBA2–2.

    Article  Google Scholar 

  32. •• Khan SA, Zhao F, Goldstein LJ, et al. Early local therapy for the primary site in de novo stage IV breast cancer: results of a randomized clinical trial (EA2108). J Clin Oncol. 2022;40(9):978–87 Findings from this prospective randomized controlled trial suggest that local therapy for the primary tumor may not translate into an overall survival benefit in patients with de novo metastatic breast cancer.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Coffey JC, Wang JH, Smith MJ, Bouchier-Hayes D, Cotter TG, Redmond HP. Excisional surgery for cancer cure: therapy at a cost. Lancet Oncol. 2003;4(12):760–8.

    Article  CAS  PubMed  Google Scholar 

  34. Chen Z, Zhang P, Xu Y, et al. Surgical stress and cancer progression: the twisted tango. Mol Cancer. 2019;18(1):132.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Rashid OM, Nagahashi M, Ramachandran S, et al. Resection of the primary tumor improves survival in metastatic breast cancer by reducing overall tumor burden. Surgery. 2013;153(6):771–8.

    Article  PubMed  Google Scholar 

  36. Bosiljcic M, Cederberg RA, Hamilton MJ, et al. Targeting myeloid-derived suppressor cells in combination with primary mammary tumor resection reduces metastatic growth in the lungs. Breast Cancer Res. 2019;21(1):103.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Choy C, Raytis JL, Smith DD, et al. Inhibition of β2-adrenergic receptor reduces triple-negative breast cancer brain metastases: the potential benefit of perioperative β-blockade. Oncol Rep. 2016;35(6):3135–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ceelen W, Pattyn P, Mareel M. Surgery, wound healing, and metastasis: recent insights and clinical implications. Crit Rev Oncol Hematol. 2014;89(1):16–26.

    Article  PubMed  Google Scholar 

  39. Hong B, Lee S, Kim Y, et al. Anesthetics and long-term survival after cancer surgery-total intravenous versus volatile anesthesia: a retrospective study. BMC Anesthesiol. 2019;19(1):233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yap A, Lopez-Olivo MA, Dubowitz J, Hiller J, Riedel B. Anesthetic technique and cancer outcomes: a meta-analysis of total intravenous versus volatile anesthesia. Can J Anaesth. 2019;66(5):546–61.

    Article  PubMed  Google Scholar 

  41. Amann E, Huang DJ, Weber WP, et al. Disease-related surgery in patients with distant metastatic breast cancer. Eur J Surg Oncol. 2013;39(11):1192–8.

    Article  CAS  PubMed  Google Scholar 

  42. Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L. Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol. 2011;9(1):16–32.

    Article  PubMed  Google Scholar 

  43. Rozeboom B, Dey N, De P. ER+ metastatic breast cancer: past, present, and a prescription for an apoptosis-targeted future. Am J Cancer Res. 2019;9(12):2821–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Spring LM, Wander SA, Andre F, Moy B, Turner NC, Bardia A. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future. Lancet. 2020;395(10226):817–27.

    Article  CAS  PubMed  Google Scholar 

  45. Bjelic-Radisic V, Fitzal F, Knauer M, et al. 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;20(1):392.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Fairweather M, Jiang W, Keating NL, Freedman RA, King TA, Nakhlis F. Morbidity of local therapy for locally advanced metastatic breast cancer: an analysis of the Surveillance, Epidemiology, and End Results (SEER)-Medicare Registry. Breast Cancer Res Treat. 2018;169(2):287–93.

    Article  PubMed  Google Scholar 

  47. Makhlin I, Fox K. Oligometastatic breast cancer: is this a curable entity? A contemporary review of the literature. Curr Oncol Rep. 2020;22(2):15.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Jain SK, Dorn PL, Chmura SJ, Weichselbaum RR, Hasan Y. Incidence and implications of oligometastatic breast cancer. American Society of Clinical Oncology: In; 2012.

    Book  Google Scholar 

  49. Trovo M, Furlan C, Polesel J, et al. Radical radiation therapy for oligometastatic breast cancer: results of a prospective phase II trial. Radiother Oncol. 2018;126(1):177–80.

    Article  PubMed  Google Scholar 

  50. 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(3):878–86.

    Article  PubMed  Google Scholar 

  51. Zheng Y, Zhong G, Yu K, Lei K, Yang Q. Individualized prediction of survival benefit from locoregional surgical treatment for patients with metastatic breast cancer. Front Oncol. 2020;10:148.

    Article  PubMed  PubMed Central  Google Scholar 

  52. De Wit A, Arbion F, Desille-Gbaguidi H, Avigdor S, Body G, Ouldamer L. Role of surgery in patients with synchronous metastatic breast cancer: is there a need for axillary lymph node removal? J Gynecol Obstet Hum Reprod. 2020;50(4):101771.

    Article  PubMed  Google Scholar 

  53. Wu SG, Li FY, Chen Y, et al. Therapeutic role of axillary lymph node dissection in patients with stage IV breast cancer: a population-based analysis. J Cancer Res Clin Oncol. 2017;143(3):467–74.

    Article  PubMed  Google Scholar 

  54. Tan Y, Li X, Chen H, et al. Hormone receptor status may impact the survival benefit of surgery in stage iv breast cancer: a population-based study. Oncotarget. 2016;7(43):70991–1000.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Kim YJ, Jung SY, Kim K. Survival benefit of radiotherapy after surgery in de novo stage IV breast cancer: a population-based propensity-score matched analysis. Scientific reports. 2019;9(1):8527.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Kim BH, Kim S, Kim YI, et al. Development of an individualized prediction calculator for the benefit of postoperative radiotherapy in patients with surgically resected de novo stage IV breast cancer. Cancers (Basel). 2020;12(8):2103.

    Article  CAS  PubMed  Google Scholar 

  57. Kucharczyk MJ, Parpia S, Walker-Dilks C, Banfield L, Swaminath A. Ablative therapies in metastatic breast cancer: a systematic review. Breast Cancer Res Treat. 2017;164(1):13–25.

    Article  PubMed  Google Scholar 

  58. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051–8.

    Article  PubMed  Google Scholar 

  59. Manders K, van de Poll-Franse LV, Creemers GJ, et al. Clinical management of women with metastatic breast cancer: a descriptive study according to age group. BMC Cancer. 2006;6(6):179.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Coleman RE, Smith P, Rubens RD. Clinical course and prognostic factors following bone recurrence from breast cancer. Br J Cancer. 1998;77(2):336–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lee SJ, Park S, Ahn HK, et al. Implications of bone-only metastases in breast cancer: favorable preference with excellent outcomes of hormone receptor positive breast cancer. Cancer Res Treat. 2011;43(2):89–95.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Ahn SG, Lee HM, Cho SH, et al. Prognostic factors for patients with bone-only metastasis in breast cancer. Yonsei Med J. 2013;54(5):1168–77.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Brastianos PK, Carter SL, Santagata S, et al. Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets. Cancer Discov. 2015;5(11):1164–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Akahane T, Kanomata N, Harada O, et al. Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions. BMC Cancer. 2020;20(1):944.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Erol T, İmamoğlu NE, Aydin B, et al. Primary tumor resection for initially staged IV breast cancer: An emphasis on programmed death-ligand 1 expression, promoter methylation status, and survival. Medicine. 2019;98(33):e16773.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Manson QF, Schrijver W, Ter Hoeve ND, Moelans CB, van Diest PJ. Frequent discordance in PD-1 and PD-L1 expression between primary breast tumors and their matched distant metastases. Clin Exp Metastasis. 2019;36(1):29–37.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA

    Jennifer K. Plichta & Mahsa Taskindoust

  2. Duke Cancer Institute, Durham, NC, USA

    Jennifer K. Plichta

  3. Department of Population Health Sciences, Duke University Medical Center, Durham, NC, USA

    Jennifer K. Plichta

  4. Department of Surgery, Yale School of Medicine, New Haven, CT, USA

    Rachel A. Greenup

  5. Yale Smilow Cancer Center, New Haven, CT, USA

    Rachel A. Greenup

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  1. Jennifer K. Plichta
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Correspondence to Jennifer K. Plichta.

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Jennifer Plichta is an unpaid member of the Metastatic Breast Cancer Subcommittee for the American Joint Committee on Cancer. Mahsa Taskindoust and Rachel Greenup declare that they have no competing interests.

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Plichta, J.K., Taskindoust, M. & Greenup, R.A. Surgery in the Setting of Metastatic Breast Cancer. Curr Breast Cancer Rep 15, 37–47 (2023). https://doi.org/10.1007/s12609-023-00476-4

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