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Journal of Neuro-Oncology

, Volume 93, Issue 2, pp 243–251 | Cite as

Identification of patients who may benefit from the prophylactic cranial radiotherapy among breast cancer patients with brain metastasis

  • Pinar Saip
  • Irfan Cicin
  • Yesim Eralp
  • Hakan Karagol
  • Seden Kucucuk
  • Ruşen Cosar Alas
  • Ekrem Yavuz
  • Maktav Dincer
  • Esra Saglam
  • Erkan Topuz
Clinical study - Patient Study

Abstract

Background To identify the candidates for prophylactic cranial radiotherapy (PCI) among the patients with early and advanced-stage breast cancer. Methods The demographic, pathologic and clinical features and survival results of 182 brain metastatic breast cancer patients treated with cranial radiotherapy were examined. Results Early stage patients who progressed with isolated brain metastasis had longer survival (13 months vs. 4 months P = 0.006). Lobular/mixed type histology (P = 0.033), high nuclear (P = 0.046) and high histological grade (P = 0.034) were the prognostic factors for isolated brain metastases. The most significant factor for the time to brain metastasis was the number of involved of lymph nodes (P = 0.004). In 60% of 148 patients with metastatic breast cancer, a progression with isolated brain metastasis was developed while the systemic disease was under control. Isolated brain metastasis progression was related to the presence of the hepatic metastasis at the first relapse (P = 0.001) and with ErbB-2 overexpression (P = 0.034). The time to the brain metastasis from the first extracerabral metastasis was associated with the high nuclear grade (P = 0.040) and with chemoresistance (P = 0.037). The median survival time after the brain metastases in chemosensitive patients was longer than in chemoresistant patients (8 months vs. 3 months P = 0.044). In chemoresistant patients (P = 0.0028) and/or in triple negative patients (P = 0.05) the development of the brain metastasis was early and the survival after brain metastasis was short. Discussions Since there is a tendency to early brain metastasis in early stage patients with high-grade, lobular/mixed type histology tumors and with a high number of involved lymph nodes, the value of PCI can be explored in these patients by a well designed prospective trial. Advanced stage chemosensitive patients with ErbB-2 over-expression and/or with hepatic metastasis at their first relapse may be candidates for PCI. There is no place for PCI in chemoresistant and triple-negative breast cancer patients.

Keywords

Breast cancer Brain metastasis Prophylactic cranial irradiation 

References

  1. 1.
    Greenlee RT, Murray T, Bolden S et al (2000) Cancer statistics, 2000. CA Cancer J Clin 50:7–33. doi: 10.3322/canjclin.50.1.7 PubMedCrossRefGoogle Scholar
  2. 2.
    DiStefano A, Yong Yap Y, Hortobagyi GN et al (1979) The natural history of breast cancer patients with brain metastases. Cancer 44:1913–1918. doi:10.1002/1097-0142(197911)44:5<1913::AID-CNCR2820440554>3.0.CO;2-DPubMedCrossRefGoogle Scholar
  3. 3.
    Paterson AHG, Agarwal M, Lees A et al (1982) Brain metastases in breast cancer patients receiving adjuvant chemotherapy. Cancer 49:651–654. doi:10.1002/1097-0142(19820215)49:4<651::AID-CNCR2820490408>3.0.CO;2-XPubMedCrossRefGoogle Scholar
  4. 4.
    Ahmann FR, Jones SE, Moon TE (1988) The effect of prior adjuvant chemotherapy on survival in metastatic breast cancer. J Surg Oncol 37:116–122. doi: 10.1002/jso.2930370211 PubMedCrossRefGoogle Scholar
  5. 5.
    Pierga JY, Asselain B, Jouve M et al (2001) Effect of adjuvant chemotherapy on outcome in patients with metastatic breast carcinoma treated with first-line doxorubicin-containing chemotherapy. Cancer 91:1079–1089. doi:10.1002/1097-0142(20010315)91:6<1079::AID-CNCR1103>3.0.CO;2-SPubMedCrossRefGoogle Scholar
  6. 6.
    Carey LA, Ewend MG, Metzger R et al (2004) Central nervous system metastases in women after multimodality therapy for high risk breast cancer. Breast Cancer Res Treat 88:273–280. doi: 10.1007/s10549-004-0999-3 PubMedCrossRefGoogle Scholar
  7. 7.
    Crivellari D, Pagani O, Veronesi A et al (2001) International Breast Cancer Study Group. High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel. Ann Oncol 12:353–356. doi: 10.1023/A:1011132609055 PubMedCrossRefGoogle Scholar
  8. 8.
    Tham YL, Sexton K, Kramer R et al (2006) Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 107:696–704. doi: 10.1002/cncr.22041 PubMedCrossRefGoogle Scholar
  9. 9.
    Gabos Z, Sinha R, Hanson J et al (2006) Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J Clin Oncol 24:5658–5663. doi: 10.1200/JCO.2006.07.0250 PubMedCrossRefGoogle Scholar
  10. 10.
    Palmieri D, Bronder JL, Herring JM et al (2007) Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Res 67:4190–4198. doi: 10.1158/0008-5472.CAN-06-3316 PubMedCrossRefGoogle Scholar
  11. 11.
    Burstein HJ, Lieberman G, Slamon DJ et al (2005) Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy. Ann Oncol 16:1772–1777. doi: 10.1093/annonc/mdi371 PubMedCrossRefGoogle Scholar
  12. 12.
    Gori S, Rimondini S, De Angelis V et al (2007) Central nervous system metastases in HER-2 positive metastatic breast cancer patients treated with trastuzumab: incidence, survival, and risk factors. Oncologist 12:766–773. doi: 10.1634/theoncologist.12-7-766 PubMedCrossRefGoogle Scholar
  13. 13.
    Shmueli E, Wigler N, Inbar M (2004) Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment. Eur J Cancer 40:379–382. doi: 10.1016/j.ejca.2003.09.018 PubMedCrossRefGoogle Scholar
  14. 14.
    Lower EE, Drosick DR, Blau R et al (2003) Increased rate of brain metastasis with trastuzumab therapy not associated with impaired survival. Clin Breast Cancer 4:114–119. doi: 10.3816/CBC.2003.n.016 PubMedCrossRefGoogle Scholar
  15. 15.
    Clayton AJ, Danson S, Jolly S et al (2004) Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 91:639–643PubMedGoogle Scholar
  16. 16.
    Bendell JC, Domchek SM, Burstein HJ et al (2003) Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97:2972–2977. doi: 10.1002/cncr.11436 PubMedCrossRefGoogle Scholar
  17. 17.
    Fokstuen T, Wilking N, Rutqvist LE et al (2000) Radiation therapy in the management of brain metastases from breast cancer. Breast Cancer Res Treat 62:211–216. doi: 10.1023/A:1006486423827 PubMedCrossRefGoogle Scholar
  18. 18.
    Lin NU, Bellon JR, Winer EP (2004) CNS metastases in breast cancer. J Clin Oncol 22:3608–3617. doi: 10.1200/JCO.2004.01.175 PubMedCrossRefGoogle Scholar
  19. 19.
    Saip P, Cicin I, Eralp Y et al (2008) Factors affecting the prognosis of breast cancer patients with brain metastases. Breast doi: 10.1016/j.breast.2008.03.004
  20. 20.
    Aupérin A, Arriagada R, Pignon JP et al (1999) Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic cranial irradiation overview collaborative group. N Engl J Med 341:476–484. doi: 10.1056/NEJM199908123410703 PubMedCrossRefGoogle Scholar
  21. 21.
    Slotman B, Faivre-Finn C, Kramer G et al (2007) EORTC radiation oncology group and lung cancer group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 357:664–672. doi: 10.1056/NEJMoa071780 PubMedCrossRefGoogle Scholar
  22. 22.
    Tsukada Y, Fouad A, Pickren JW et al (1983) Central nervous system metastasis from breast carcinoma: autopsy study. Cancer 52:2349–2354. doi:10.1002/1097-0142(19831215)52:12<2349::AID-CNCR2820521231>3.0.CO;2-BPubMedCrossRefGoogle Scholar
  23. 23.
    Samaan NA, Buzdar AU, Aldinger KA et al (1981) Estrogen receptor: a prognostic factor in breast cancer. Cancer 47:554–560. doi:10.1002/1097-0142(19810201)47:3<554::AID-CNCR2820470322>3.0.CO;2-WPubMedCrossRefGoogle Scholar
  24. 24.
    Maki DD, Grossman RI (2000) Patterns of disease spread in metastatic breast carcinoma: influence of estrogen and progesterone receptor status. AJNR Am J Neuroradiol 21:1064–1066PubMedGoogle Scholar
  25. 25.
    Gonzalez-Angulo AM, Cristofanilli M, Strom EA et al (2004) Central nervous system metastases in patients with high-risk breast carcinoma after multimodality treatment. Cancer 101:1760–1766. doi: 10.1002/cncr.20530 PubMedCrossRefGoogle Scholar
  26. 26.
    Miller KD, Weathers T, Haney LG et al (2003) Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival. Ann Oncol 14:1072–1077. doi: 10.1093/annonc/mdg300 PubMedCrossRefGoogle Scholar
  27. 27.
    Ryberg M, Nielsen D, Osterlind K et al (2005) Predictors of central nervous system metastasis in patients with metastatic breast cancer. A competing risk analysis of 579 patients treated with epirubicin-based chemotherapy. Breast Cancer Res Treat 91:217–225. doi: 10.1007/s10549-005-0323-x PubMedCrossRefGoogle Scholar
  28. 28.
    Lin NU, Winer EP (2007) Brain metastases: the HER2 paradigm. Clin Cancer Res 13:1648–1655. doi: 10.1158/1078-0432.CCR-06-2478 PubMedCrossRefGoogle Scholar
  29. 29.
    Cleator S, Heller W, Coombes RC (2007) Triple-negative breast cancer: therapeutic options. Lancet Oncol 8(3):235–244. doi: 10.1016/S1470-2045(07)70074-8 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Pinar Saip
    • 1
  • Irfan Cicin
    • 2
  • Yesim Eralp
    • 1
  • Hakan Karagol
    • 2
  • Seden Kucucuk
    • 3
  • Ruşen Cosar Alas
    • 4
  • Ekrem Yavuz
    • 5
  • Maktav Dincer
    • 3
  • Esra Saglam
    • 3
  • Erkan Topuz
    • 1
  1. 1.Department of Medical Oncology, Institute of OncologyIstanbul UniversityIstanbulTurkey
  2. 2.Department of Medical Oncology, Faculty of MedicineTrakya UniversityEdirneTurkey
  3. 3.Department of Radiation Oncology, Institute of OncologyIstanbul UniversityIstanbulTurkey
  4. 4.Department of Radiation Oncology, Faculty of MedicineTrakya UniversityEdirneTurkey
  5. 5.Department of Pathology, Faculty of MedicineIstanbul UniversityIstanbulTurkey

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