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The Impact of Primary Tumor Surgery on Survival in HER2 Positive Stage IV Breast Cancer Patients in the Current Era of Targeted Therapy

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

Abstract

Objective

We sought to examine the impact of primary tumor resection on survival in HER2+ stage IV breast cancer patients in the era of HER2 targeted therapy.

Methods

We conducted a retrospective cohort study of women with HER2+ stage IV breast cancer in the National Cancer Database from 2010 to 2012 comparing those who did and did not undergo definitive breast surgery.

Results

Of 3231 patients, treatment included primary site surgery in 35.0%; chemo/targeted therapy in 89.4%; endocrine therapy in 37.7%; and radiation in 31.8%. Surgery was associated with Medicare/other government (OR 1.36, 95% CI 1.03–1.81) or private insurance (OR 1.93, 95% CI 1.53–2.42) versus none/Medicaid, radiation (OR 2.10, 95% CI 1.76–2.51), chemo/targeted therapy (OR 1.99, 95% CI 1.47–2.70), and endocrine therapy (OR 1.73, 95% CI 1.40–2.14). Non-Hispanic Black versus White patients (OR 0.68, 95% CI 0.53–0.87) were less likely to have surgery. Overall mortality was associated with insurance (Medicare/other government versus none/Medicaid, HR 0.36, p < 0.0001), receipt of chemo/targeted therapy (HR 0.76, p = 0.008), endocrine therapy (HR 0.70, p = 0.0006), and radiation therapy (HR 1.33, p = 0.0009), NH Black versus White race/ethnicity (HR 1.39, p = 0.002), visceral versus bone-only metastases (HR 1.44, p = 0.0003), and lowest versus highest income quartile (HR 1.36, p = 0.01). Propensity score analysis showed surgery was associated with improved survival versus no surgery (HR 0.56, 95% CI 0.40–0.77).

Conclusions

Surgery of the primary site for metastatic HER2+ breast cancer is associated with improved overall survival in selected patients.

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References

  1. Lu S, Wu J, Fang Y, et al. The impact of surgical excision of the primary tumor in stage IV breast cancer on survival: a meta-analysis. Oncotarget. 2018.

  2. National Comprehensive Cancer Network. Breast Cancer (Version 1.2019). Accessed April 1, 2019.

  3. 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(6):776–782.

    PubMed  Google Scholar 

  4. 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(12):3345–3351.

    PubMed  Google Scholar 

  5. 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(8):2187–2194.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  7. 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(18):2743–2749.

    PubMed  Google Scholar 

  8. 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(1):7–12.

    PubMed  Google Scholar 

  9. Barbie TU, Golshan M. De novo stage 4 metastatic breast cancer: a surgical disease? Ann Surg Oncol. 2018;25(11):3109–3111.

    PubMed  Google Scholar 

  10. Cady B, Nathan NR, Michaelson JS, Golshan M, Smith BL. Matched pair analyses of stage IV breast cancer with or without resection of primary breast site. Ann Surg Oncol. 2008;15(12):3384–3395.

    CAS  PubMed  Google Scholar 

  11. 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(2):459–465.

    PubMed  PubMed Central  Google Scholar 

  12. 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):3141–3149.

    PubMed  Google Scholar 

  13. Soran A. The role of loco-regional treatment in long-term quality of life in de novo stage IV breast cancer patient: protocol MF07-01Q. Paper presented at: Plenary presentation at the 20th annual meeting of the American Society of Breast Surgeons; May 4, 2019, 2019; Dallas, Texas.

  14. 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(13):1380–1388.

    PubMed  Google Scholar 

  15. Hudis CA. Trastuzumab — mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39–51.

    CAS  PubMed  Google Scholar 

  16. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177.

    CAS  PubMed  Google Scholar 

  17. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244(4905):707.

    CAS  PubMed  Google Scholar 

  18. Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol. 2010;28(1):92–98.

    CAS  PubMed  Google Scholar 

  19. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–792.

    CAS  PubMed  Google Scholar 

  20. Swain SM, Miles D, Kim S-B, et al. End-of-study analysis from the phase III, randomized, double-blind, placebo (Pla)-controlled CLEOPATRA study of first-line (1L) pertuzumab (P), trastuzumab (H), and docetaxel (D) in patients (pts) with HER2-positive metastatic breast cancer (MBC). J Clin Oncol. 2019;37(15_suppl):1020–1020.

  21. Baselga J, Cortés J, Kim S-B, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109–119.

    CAS  PubMed  Google Scholar 

  22. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355(26):2733–2743.

    CAS  PubMed  Google Scholar 

  23. Jackisch C, Stroyakovskiy D, Pivot X, et al. Subcutaneous vs intravenous trastuzumab for patients with ERBB2-positive early breast cancer. JAMA Oncol. 2019;5(5):e190339.

    PubMed  PubMed Central  Google Scholar 

  24. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–1791.

    CAS  PubMed  Google Scholar 

  25. Giuliano AE, Connolly JL, Edge SB, et al. Breast cancer—major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(4):290–303.

    Google Scholar 

  26. American College of Surgeons. CS site-specific factor 15, HER2: summary result of testing. http://web2.facs.org/cstage0205/breast/Breast_sbg.html. Accessed 1 Nov 2018.

  27. American College of Surgeons. NCDB Analytic Stage Group. http://ncdbpuf.facs.org/content/analytic-stage-group-ajcc-alphanumeric. Accessed 1 Nov 2018.

  28. American College of Surgeons. Charlson/Deyo score. http://ncdbpuf.facs.org/content/charlsondeyo-comorbidity-index. Accessed 1 Nov 2018.

  29. American College of Surgeons. Surgery of the primary site: BREAST. http://ncdbpuf.facs.org/content/breast. Accessed 1 Nov 2018.

  30. American College of Surgeons. Spanish origin. http://ncdbpuf.facs.org/content/spanish-origin. Accessed 1 Nov 2018.

  31. American College of Surgeons. Immunotherapy. http://ncdbpuf.facs.org/content/immunotherapy. Accessed 1 Nov 2018.

  32. Fisher B, Gunduz N, Coyle J, Rudock C, Saffer E. Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res. 1989;49(8):1996.

    CAS  PubMed  Google Scholar 

  33. Ten Kate M, Hofland LJ, Van Grevenstein WMU, Van Koetsveld PV, Jeekel J, Van Eijck CHJ. Influence of proinflammatory cytokines on the adhesion of human colon carcinoma cells to lung microvascular endothelium. Int J Cancer. 2004;112(6):943–950.

    PubMed  Google Scholar 

  34. Benish M, Bartal I, Goldfarb Y, et al. Perioperative use of β-blockers and COX-2 inhibitors may improve immune competence and reduce the risk of tumor metastasis. Ann Surg Oncol. 2008;15(7):2042–2052.

    PubMed  Google Scholar 

  35. Shien T, Iwata H. Significance of primary lesion resection in stage IV breast cancer. Jpn J Clin Oncol. 2017;47(5):381–384.

    PubMed  Google Scholar 

  36. Kakarala M, Wicha MS. Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol. 2008;26(17):2813–2820.

    PubMed  PubMed Central  Google Scholar 

  37. Danna EA, Sinha P, Gilbert M, Clements VK, Pulaski BA, Ostrand-Rosenberg S. Surgical removal of primary tumor reverses tumor-induced immunosuppression despite the presence of metastatic disease. Cancer Res. 2004;64(6):2205–2211.

    CAS  PubMed  Google Scholar 

  38. Kim M-Y, Oskarsson T, Acharyya S, et al. Tumor self-seeding by circulating cancer cells. Cell. 2009;139(7):1315–1326.

    PubMed  PubMed Central  Google Scholar 

  39. Norton L, Massagué J. Is cancer a disease of self-seeding? Nat Med. 2006;12(8):875–878.

    CAS  PubMed  Google Scholar 

  40. Zambetti M, Montemurro F, Morandi P, et al. Safety profile of subcutaneous trastuzumab for the treatment of patients with HER2-positive early or locally advanced breast cancer: primary analysis of the SCHEARLY study. Eur J Cancer. 2018;105:61–70.

    CAS  PubMed  Google Scholar 

  41. 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. 2015.

  42. 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):537–544.

    PubMed  PubMed Central  Google Scholar 

  43. 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(15_suppl):1006–1006.

    Google Scholar 

  44. National Institutes of Health Clinical Trials. A randomized phase III trial of the value of early local therapy for the intact primary tumor in patients with metastatic breast cancer. https://clinicaltrials.gov/ct2/show/NCT01242800?term=NCT01242800&rank=1. Accessed 1 Apr 2019.

  45. UMIN Clinical Trials Registry. A randomized controlled trial comparing primary tumor resection plus systemic therapy with systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC). https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006333. Accessed 1 Apr 2019.

  46. Neuman HB, Morrogh M, Gonen M, Van Zee KJ, Morrow M, King TA. Stage IV breast cancer in the era of targeted therapy. Cancer. 2010;116(5):1226–1233.

    PubMed  PubMed Central  Google Scholar 

  47. Pons-Tostivint E, Kirova Y, Lusque A, et al. Survival impact of locoregional treatment of the primary tumor in de novo metastatic breast cancers in a large multicentric cohort study: a propensity score-matched analysis. Ann Surg Oncol. 2019;26(2):356–365.

    PubMed  Google Scholar 

  48. 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(2):367–374.

    CAS  PubMed  Google Scholar 

  49. Imkampe A, Bendall S, Bates T. The significance of the site of recurrence to subsequent breast cancer survival. Eur J Surg Oncol (EJSO). 2007;33(4):420–423.

    CAS  PubMed  Google Scholar 

  50. American College of Surgeons. Radiation therapy. http://ncdbpuf.facs.org/content/radiation-therapy. Accessed 1 Nov 2018.

  51. Sogaard M, W. Thomsen R, Bossen, Henrik Toft Sørensen H, Nørgaard M. The impact of comorbidity on cancer survival: a review. Clin Epidemiol. 2013:3.

  52. Rugo HS, Brufsky AM, Yood MU, et al. Racial disparities in treatment patterns and clinical outcomes in patients with HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2013;141(3):461–470.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Newman LA. Breast cancer in African-American women. Oncol. 2005;10(1):1–14.

    PubMed  Google Scholar 

  54. Ren J-X, Gong Y, Ling H, Hu X, Shao Z-M. Racial/ethnic differences in the outcomes of patients with metastatic breast cancer: contributions of demographic, socioeconomic, tumor and metastatic characteristics. Breast Cancer Res Treat. 2019;173(1):225–237.

    PubMed  Google Scholar 

  55. Vaz-Luis I, Lin NU, Keating NL, et al. Racial differences in outcomes for patients with metastatic breast cancer by disease subtype. Breast Cancer Res Treat. 2015;151(3):697–707.

    PubMed  Google Scholar 

  56. Cardoso F, Harbeck N, Fallowfield L, Kyriakides S, Senkus E. Locally recurrent or metastatic breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(suppl 7):vii11-vii19.

    PubMed  Google Scholar 

  57. National Comprehensive Cancer Network. Breast cancer (Version 2010). Accessed 1 Apr 2019.

  58. Howie LJ, Scher NS, Amiri-Kordestani L, et al. FDA approval summary: pertuzumab for adjuvant treatment of HER2-positive early breast cancer. Clin Cancer Res. 2019;25(10):2949–2955.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society and the data used in the study are derived from a de-identified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data.

Disclosures

The authors have no disclosures. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Surgery, Division of Surgical Oncology, School of Medicine, Loma Linda University, Loma Linda, CA, USA

    Ross Mudgway B.S., Carlos Chavez de Paz Villanueva M.D., M.P.H., Ann C. Lin M.D., Maheswari Senthil M.D., Carlos A. Garberoglio M.D. & Sharon S. Lum M.D., F.A.C.S.

  2. School of Medicine, University of California, Riverside, Riverside, CA, USA

    Ross Mudgway B.S. & Sharon S. Lum M.D., F.A.C.S.

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  1. Ross Mudgway B.S.
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  2. Carlos Chavez de Paz Villanueva M.D., M.P.H.
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Mudgway, R., Chavez de Paz Villanueva, C., Lin, A.C. et al. The Impact of Primary Tumor Surgery on Survival in HER2 Positive Stage IV Breast Cancer Patients in the Current Era of Targeted Therapy. Ann Surg Oncol 27, 2711–2720 (2020). https://doi.org/10.1245/s10434-020-08310-2

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