Skip to main content

Advertisement

SpringerLink
Log in

Systemic treatment after whole-brain radiotherapy may improve survival in RPA class II/III breast cancer patients with brain metastasis

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Whole brain radiotherapy (WBRT) is the most widely used treatment for brain metastasis (BM), especially for patients with multiple intracranial lesions. The purpose of this study was to examine the efficacy of systemic treatments following WBRT in breast cancer patients with BM who had different clinical characteristics, based on the classification of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) and the breast cancer-specific Graded Prognostic Assessment (Breast-GPA). One hundred and one breast cancer patients with BM treated between 2006 and 2010 were analyzed. The median interval between breast cancer diagnosis and identification of BM in the triple-negative patients was shorter than in the luminal A subtype (26 vs. 36 months, respectively; P = 0.021). Univariate analysis indicated that age at BM diagnosis, Karnofsky performance status/recursive partitioning analysis (KPS/RPA) classes, number of BMs, primary tumor control, extracranial metastases and systemic treatment following WBRT were significant prognostic factors for overall survival (OS) (P < 0.05). Multivariate analysis revealed that KPS/RPA classes and systemic treatments following WBRT remained the significant prognostic factors for OS. For RPA class I, the median survival with and without systemic treatments following WBRT was 25 and 22 months, respectively (P = 0.819), while for RPA class II/III systemic treatments significantly improved OS from 7 and 2 months to 11 and 5 months, respectively (P < 0.05). Our results suggested that triple-negative patients had a shorter interval between initial diagnosis and the development of BM than luminal A patients. Systemic treatments following WBRT improved the survival of RPA class II/III patients.

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
Fig. 2

Similar content being viewed by others

References

  1. Niwinska A, Murawska M, Pogoda K (2010) Breast cancer brain metastases: differences in survival depending on biological subtype, RPA RTOG prognostic class and systemic treatment after whole-brain radiotherapy (WBRT). Ann Oncol 21:942–948. doi:10.1093/annonc/mdp407

    Article  PubMed  CAS  Google Scholar 

  2. Niwinska A, Pogoda K, Murawska M, Niwinski P (2011) Factors influencing survival in patients with breast cancer and single or solitary brain metastasis. Eur J Surg Oncol 37:635–642. doi:10.1016/j.ejso.2011.05.002

    Article  PubMed  CAS  Google Scholar 

  3. Chargari C, Idrissi HR, Pierga JY, Bollet MA, Dieras V, Campana F, Cottu P, Fourquet A, Kirova YM (2011) Preliminary results of whole brain radiotherapy with concurrent trastuzumab for treatment of brain metastases in breast cancer patients. Int J Radiat Oncol Biol Phys 81:631–636. doi:10.1016/j.ijrobp.2010.06.057

    Article  PubMed  Google Scholar 

  4. Niwinska A, Murawska M, Pogoda K (2010) Breast cancer subtypes and response to systemic treatment after whole-brain radiotherapy in patients with brain metastases. Cancer 116:4238–4247. doi:10.1002/cncr.25391

    Article  PubMed  Google Scholar 

  5. Arslan UY, Oksuzoglu B, Aksoy S, Harputluoglu H, Turker I, Ozisik Y, Dizdar O, Altundag K, Alkis N, Zengin N (2011) Breast cancer subtypes and outcomes of central nervous system metastases. Breast 20:562–567. doi:10.1016/j.breast.2011.07.017

    Article  PubMed  Google Scholar 

  6. Koboldt DCFR, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF et al (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70. doi:10.1038/nature11412

    Article  CAS  Google Scholar 

  7. Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W (2008) A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 70:510–514. doi:10.1016/j.ijrobp.2007.06.074

    Article  PubMed  Google Scholar 

  8. Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, Bhatt A, Jensen AW, Brown PD, Shih H, Kirkpatrick J, Schwer A, Gaspar LE, Fiveash JB, Chiang V, Knisely J, Sperduto CM, Mehta M (2010) Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys 77:655–661. doi:10.1016/j.ijrobp.2009.08.025

    Article  PubMed  Google Scholar 

  9. Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J, Bhatt A, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M (2012) Effect of tumor subtype on survival and the graded prognostic assessment for patients with breast cancer and brain metastases. Int J Radiat Oncol Biol Phys 82:2111–2117. doi:10.1016/j.ijrobp.2011.02.027

    Article  PubMed  Google Scholar 

  10. Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J, Bhatt A, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M (2012) Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 30:419–425. doi:10.1200/JCO.2011.38.0527

    Article  PubMed  Google Scholar 

  11. Nam BH, Kim SY, Han HS, Kwon Y, Lee KS, Kim TH, Ro J (2008) Breast cancer subtypes and survival in patients with brain metastases. Breast Cancer Res 10:R20. doi:10.1186/bcr1870

    Article  PubMed  Google Scholar 

  12. Eichler AF, Kuter I, Ryan P, Schapira L, Younger J, Henson JW (2008) Survival in patients with brain metastases from breast cancer: the importance of HER-2 status. Cancer 112:2359–2367. doi:10.1002/cncr.23468

    Article  PubMed  CAS  Google Scholar 

  13. Heitz F, Harter P, Lueck HJ, Fissler-Eckhoff A, Lorenz-Salehi F, Scheil-Bertram S, Traut A, du Bois A (2009) Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases. Eur J Cancer 45:2792–2798. doi:10.1016/j.ejca.2009.06.027

    Article  PubMed  CAS  Google Scholar 

  14. Metro G, Foglietta J, Russillo M, Stocchi L, Vidiri A, Giannarelli D, Crino L, Papaldo P, Mottolese M, Cognetti F, Fabi A, Gori S (2011) Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine. Ann Oncol 22:625–630. doi:10.1093/annonc/mdq434

    Article  PubMed  CAS  Google Scholar 

  15. Lin NU, Eierman W, Greil R, Campone M, Kaufman B, Steplewski K, Lane SR, Zembryki D, Rubin SD, Winer EP (2011) Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases. J Neurooncol 105:613–620. doi:10.1007/s11060-011-0629-y

    Article  PubMed  CAS  Google Scholar 

  16. Abboud M, Saghir NS, Salame J, Geara FB (2010) Complete response of brain metastases from breast cancer overexpressing Her-2/neu to radiation and concurrent Lapatinib and Capecitabine. Breast J 16:644–646. doi:10.1111/j.1524-4741.2010.00980.x

    Article  PubMed  Google Scholar 

  17. Kim HJ, Im SA, Keam B, Kim YJ, Han SW, Kim TM, Oh DY, Kim JH, Lee SH, Chie EK, Han W, Kim DW, Kim TY, Noh DY, Heo DS, Park IA, Bang YJ, Ha SW (2012) Clinical outcome of central nervous system metastases from breast cancer: differences in survival depending on systemic treatment. J Neurooncol 106:303–313. doi:10.1007/s11060-011-0664-8

    Article  PubMed  Google Scholar 

  18. Mata JF, Garcia-Manteiga JM, Lostao MP, Fernandez-Veledo S, Guillen-Gomez E, Larrayoz IM, Lloberas J, Casado FJ, Pastor-Anglada M (2001) Role of the human concentrative nucleoside transporter (hCNT1) in the cytotoxic action of 5[Prime]-deoxy-5-fluorouridine, an active intermediate metabolite of capecitabine, a novel oral anticancer drug. Mol Pharmacol 59:1542–1548

    PubMed  CAS  Google Scholar 

  19. Pienkowski T, Zielinski CC (2010) Trastuzumab treatment in patients with breast cancer and metastatic CNS disease. Ann Oncol 21:917–924. doi:10.1093/annonc/mdp353

    Article  PubMed  CAS  Google Scholar 

  20. Stemmler HJSM, Willems A, Bernhard H, Harbeck N, Heinemann V (2007) Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood–brain barrier. Anticancer Drugs 18:23–28

    Article  PubMed  CAS  Google Scholar 

  21. Park IH, Ro J, Lee KS, Nam BH, Kwon Y, Shin KH (2009) Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer. Ann Oncol 20:56–62. doi:10.1093/annonc/mdn539

    Article  PubMed  CAS  Google Scholar 

  22. Tomasello G, Bedard PL, de Azambuja E, Lossignol D, Devriendt D, Piccart-Gebhart MJ (2010) Brain metastases in HER2-positive breast cancer: the evolving role of lapatinib. Crit Rev Oncol Hematol 75:110–121. doi:10.1016/j.critrevonc.2009.11.003

    Article  PubMed  Google Scholar 

  23. Lin NU, Dieras V, Paul D, Lossignol D, Christodoulou C, Stemmler HJ, Roche H, Liu MC, Greil R, Ciruelos E, Loibl S, Gori S, Wardley A, Yardley D, Brufsky A, Blum JL, Rubin SD, Dharan B, Steplewski K, Zembryki D, Oliva C, Roychowdhury D, Paoletti P, Winer EP (2009) Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res 15:1452–1459. doi:10.1158/1078-0432.CCR-08-1080

    Article  PubMed  CAS  Google Scholar 

  24. Gaspar LSC, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhart R (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751

    Article  PubMed  CAS  Google Scholar 

  25. Nieder C, Marienhagen K, Astner ST, Molls M (2009) Prognostic scores in brain metastases from breast cancer. BMC cancer 9:105. doi:10.1186/1471-2407-9-105

    Article  PubMed  Google Scholar 

  26. Ahn HK, Lee S, Park YH, Sohn JH, Jo JC, Ahn JH, Jung KH, Park S, Cho EY, Lee JI, Park W, Choi DH, Huh SJ, Ahn JS, Kim SB, Im YH (2012) Prediction of outcomes for patients with brain parenchymal metastases from breast cancer (BC): a new BC-specific prognostic model and a nomogram. Neuro oncol 14:1105–1113. doi:10.1093/neuonc/nos137

    Article  PubMed  CAS  Google Scholar 

  27. Park YH, Park MJ, Ji SH, Yi SY, Lim DH, Nam DH, Lee JI, Park W, Choi DH, Huh SJ, Ahn JS, Kang WK, Park K, Im YH (2009) Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients. Br J Cancer 100:894–900. doi:10.1038/sj.bjc.6604941

    Article  PubMed  CAS  Google Scholar 

  28. Fokas E, Henzel M, Hamm K, Grund S, Engenhart-Cabillic R (2012) Brain metastases in breast cancer: analysis of the role of HER2 status and treatment in the outcome of 94 patients. Tumori 98:768–774. doi:10.1700/1217.13502

    PubMed  Google Scholar 

  29. Bartsch R, Rottenfusser A, Wenzel C, Dieckmann K, Pluschnig U, Altorjai G, Rudas M, Mader RM, Poetter R, Zielinski CC, Steger GG (2007) Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer. J Neurooncol 85:311–317. doi:10.1007/s11060-007-9420-5

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None.

Ethical standard

Ethical approval was not required.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China

    Qian Zhang, XiaoLi Yu, JinLi Ma, Gang Cai, ZhaoZhi Yang, Lu Cao, XingXing Chen, XiaoMao Guo & JiaYi Chen

  2. Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China

    Qian Zhang, XiaoLi Yu, JinLi Ma, Gang Cai, ZhaoZhi Yang, Lu Cao, XingXing Chen, XiaoMao Guo & JiaYi Chen

  3. Department of Radiation Oncology, Shanghai Minhang District Cancer Hospital, 106 Ruili Road, Shanghai, 200240, China

    Jian Chen

Authors
  1. Qian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. XiaoLi Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. JinLi Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gang Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. ZhaoZhi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lu Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. XingXing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. XiaoMao Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. JiaYi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to JiaYi Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, Q., Chen, J., Yu, X. et al. Systemic treatment after whole-brain radiotherapy may improve survival in RPA class II/III breast cancer patients with brain metastasis. J Neurooncol 114, 181–189 (2013). https://doi.org/10.1007/s11060-013-1169-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-013-1169-4

Keywords

Search

Navigation