Skip to main content

Advertisement

SpringerLink
Log in

Clinicopathological and surgical factors associated with long-term survival in patients with HER2-positive metastatic breast cancer

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Trastuzumab-based treatment has dramatically improved the outcomes of HER2-positive (HER2+) metastatic breast cancer (MBC) patients, with some patients achieving prolonged survival times. In this study, we aim to identify factors that are associated with long-term survival. Patients with HER2+ MBC treated with anti-HER2 target therapy were identified. Patients were grouped according to overall survival (OS) and categorized as long-term survivors (LTS, OS ≥ 5 years), or non-long-term survivors (non-LTS, OS < 5 years). Descriptive statistics and multivariable logistic regression modeling were used. A sensitivity analysis was carried out, including only patients diagnosed before 2007; therefore, 5 years of potential follow-up was possible. 1063 patients with HER2+ MBC diagnosed between 1994 and 2012 and treated with anti-HER2 therapy were identified. Among them, 154 (14.5 %) patients were categorized as LTS (median OS 92.2 months). Among LTS, 63.4 % were HR-positive and 32 % had de novo stage IV disease. Hormone receptor positivity (OR) 1.69; 95 % CI 1.17–2.44), resection of metastases (OR 2.38; 95 % CI 1.53–3.69), and primary breast surgery in patients with de novo stage IV (OR 2.88; 95 % CI 1.47–5.66) were associated with improved long-term survival. Greater number of metastatic sites (≥3 vs. 1, OR 0.41; 95 % CI 0.23–0.72) and visceral metastases (OR 0.61; 95 % CI 0.4–0.91) were associated with poor survival. Hormone receptor positivity, low burden of disease, metastasis to soft and bone tissues, and surgical management with resection of the metastatic site and the primary tumor were associated with long-term survival in patients with MBC who received anti-HER2 treatment.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Gutierrez C, Schiff R (2011) HER2: biology, detection, and clinical implications. Arch Pathol Lab Med 135:55–62

    PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Arteaga CL, Sliwkowski MX, Osborne CK et al (2012) Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol 9:16–32

    Article  CAS  Google Scholar 

  4. Liu AN, Sun P, Liu JN et al (2012) Clinicopathologic characteristics and prognostic factors in patients with operable HER-2 overexpressing breast cancer. Asian Pac J Cancer Prev 13:1197–1201

    Article  PubMed  Google Scholar 

  5. Kim JW, Kim JH, Im SA et al (2013) HER2/CEP17 ratio and HER2 immunohistochemistry predict clinical outcome after first-line trastuzumab plus taxane chemotherapy in patients with HER2 fluorescence in situ hybridization-positive metastatic breast cancer. Cancer Chemother Pharmacol 72:109–115

    Article  CAS  PubMed  Google Scholar 

  6. Giuliani R, Durbecq V, Di Leo A et al (2007) Phosphorylated HER-2 tyrosine kinase and Her-2/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC). Eur J Cancer 43:725–735

    Article  CAS  PubMed  Google Scholar 

  7. Esteva FJ, Yu D, Hung MC, Hortobagyi GN (2010) Molecular predictors of response to trastuzumab and lapatinib in breast cancer. Nat Rev Clin Oncol 7:98–107

    Article  CAS  PubMed  Google Scholar 

  8. Vaz-Luis I, Seah D, Olson EM et al (2013) Clinicopathological features among patients with advanced human epidermal growth factor-2-positive breast cancer with prolonged clinical benefit to first-line trastuzumab-based therapy: a retrospective cohort study. Clin Breast Cancer 13:254–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yardley DA, Tripathy D, Brufsky AM et al (2014) Long-term survivor characteristics in HER2-positive metastatic breast cancer from registHER. Br J Cancer 110:2756–2764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dawood S, Broglio K, Buzdar AU et al (2010) Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 28:92–98

    Article  CAS  PubMed  Google Scholar 

  11. Montemurro F, Di Cosimo S, Arpino G (2013) Human epidermal growth factor receptor 2 (HER2)-positive and hormone receptor-positive breast cancer: new insights into molecular interactions and clinical implications. Ann Oncol 24:2715–2724

    Article  CAS  PubMed  Google Scholar 

  12. Baselga J, Bradbury I, Eidtmann H et al (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 379:633–640

    Article  CAS  PubMed  Google Scholar 

  13. Untch M, Loibl S, Bischoff J et al (2012) Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol 13:135–144

    Article  CAS  PubMed  Google Scholar 

  14. De Laurentiis M, Arpino G, Massarelli E et al (2005) A meta-analysis on the interaction between HER-2 expression and response to endocrine treatment in advanced breast cancer. Clin Cancer Res 11:4741–4748

    Article  PubMed  Google Scholar 

  15. Tripathy D, Kaufman PA, Brufsky AM et al (2013) First-line treatment patterns and clinical outcomes in patients with HER2-positive and hormone receptor-positive metastatic breast cancer from registHER. Oncologist 18:501–510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Badwe R, Hawaldar R, Nair N et al (2015) Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol 16:1380–1388

    Article  PubMed  Google Scholar 

  17. Harris E, Barry M, Kell MR (2013) 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 20:2828–2834

    Article  PubMed  Google Scholar 

  18. Pagani O, Senkus E, Wood W et al (2010) International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured? J Natl Cancer Inst 102:456–463

    Article  PubMed  PubMed Central  Google Scholar 

  19. Swain SM, Baselga J, Kim SB et al (2015) Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 372:724–734

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The National Cancer Institute through The University of Texas MD Anderson’s Cancer Center Support Grant (P30 CA016672).

Author information

Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    K. Harano, R. K. Murthy, V. Valero, N. T. Ueno, G. N. Hortobagyi & M. Chavez-MacGregor

  2. Division of Cancer Prevention, Department of Health Services Research, The University of Texas MD Anderson Cancer Center, FCT9.5024, 1515 Holcombe Blvd. Unit Number: 1444, Houston, TX, 77030, USA

    X. Lei & M. Chavez-MacGregor

  3. Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    E. A. Mittendorf

  4. Texas, USA

    A. M. Gonzalez-Angulo

Authors
  1. K. Harano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X. Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. M. Gonzalez-Angulo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. K. Murthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. Valero
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. A. Mittendorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N. T. Ueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G. N. Hortobagyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. Chavez-MacGregor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Chavez-MacGregor.

Ethics declarations

Disclosures

Mariana Chavez-MacGregor has served as a consultant for Roche and Pfizer and has received funding (given to the institution) from Novartis. Rashmy Murthy has served as a consultant for Dailchi Sankyo and Genentech and has received funding (given to the institution) from Merrimack pharmaceuticals and Oncotyeron.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 27 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harano, K., Lei, X., Gonzalez-Angulo, A.M. et al. Clinicopathological and surgical factors associated with long-term survival in patients with HER2-positive metastatic breast cancer. Breast Cancer Res Treat 159, 367–374 (2016). https://doi.org/10.1007/s10549-016-3933-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-016-3933-6

Keywords

Search

Navigation