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Breast Cancer Research and Treatment

, Volume 147, Issue 1, pp 103–112 | Cite as

Treatment outcomes and prognostic factors for patients with brain metastases from breast cancer of each subtype: a multicenter retrospective analysis

  • Naoki NiikuraEmail author
  • Naoki Hayashi
  • Norikazu Masuda
  • Seiki Takashima
  • Rikiya Nakamura
  • Ken-ichi Watanabe
  • Chizuko Kanbayashi
  • Mayumi Ishida
  • Yasuo Hozumi
  • Michiko Tsuneizumi
  • Naoto Kondo
  • Yoichi Naito
  • Yayoi Honda
  • Akira Matsui
  • Tomomi Fujisawa
  • Risa Oshitanai
  • Hiroyuki Yasojima
  • Yutaka Tokuda
  • Shigehira Saji
  • Hiroji Iwata
Clinical trial

Abstract

To define prognostic factors for breast cancer patients with brain metastases, compare their clinical courses and prognoses according to breast cancer subtypes, and analyze the causes of death in such patients. We retrospectively analyzed 1,466 patients diagnosed with brain metastases between April 1, 2001 and December 31, 2012, from 24 institutions of the Japan Clinical Oncology Group. Overall, 1,256 patients with brain metastases were included. The median overall survival (OS) was 8.7 months (95 % confidence interval [CI] 7.8–9.6 months). Univariate and multivariate analyses revealed that patients diagnosed with brain metastasis within 6 months of metastatic breast cancer diagnoses, asymptomatic brain disease, or HER2-positive/estrogen receptor-positive tumors had increased OS. Median OS after the development of brain metastases was 9.3 months (95 % CI 7.2–11.3) for the luminal type, 16.5 months (95 % CI 11.9–21.1) for the luminal-HER2 type, 11.5 months (95 % CI 9.1–13.8) for the HER2 type, and 4.9 months (95 % CI 3.9–5.9) for the triple-negative type. Luminal-HER2 type patients had significantly longer OS than patients with the luminal type (hazard ratio [HR] = 1.50, P < 0.0001) and triple-negative type (HR = 1.97, P < 0.0001); no significant differences were noted compared to HER2-type patients (HR = 1.19, P = 0.117). The prognosis and clinical course of patients with brain metastasis from breast cancer before and after developing brain metastases vary according to subtype. Focusing on the subtypes of breast cancer can optimize the prevention, early detection, and improved treatment of brain metastases.

Keywords

Breast cancer Brain metastases Retrospective analysis Subtype 

Notes

Acknowledgments

We would like to thank the following individuals for providing us with data on patients with brain metastases: Yasuyuki Sato, Nagoya Medical Center; Yoshimasa Kosaka, Kitasato University School of Medicine; Tsutomu Iwasa, Kinki University School of Medicine; Hiroyasu Yamashiro, Kure Medical Center/Chugoku Cancer Center; Tadahiko Shien; Okayama University Hospital; Kazuya Miyoshi, NHO Fukuyama Medical Center; Anan Keisei, Kitakyushu Municipal Medical Center, Department of Surgery; Hitoshi Arioka, Yokohama Rosai Hospital; and Maeda Shigeto, National Nagasaki Medical Center. We would also like to thank Editage for providing editorial assistance. This study was supported by the National Cancer Center Research and Development Fund (23-A-17) and Tokai University School of Medicine Research Aid, 2013.

Disclosure

There are no conflicts of interest to declare.

Supplementary material

10549_2014_3090_MOESM1_ESM.doc (60 kb)
Supplementary material 1 (DOC 60 kb)

References

  1. 1.
    Klos KJ, O’Neill BP (2004) Brain metastases. Neurologist 10(1):31–46. doi: 10.1097/01.nrl.0000106922.83090.7101.nrl.0000106922.83090.71 CrossRefPubMedGoogle Scholar
  2. 2.
    Frisk G, Svensson T, Backlund LM, Lidbrink E, Blomqvist P, Smedby KE (2012) Incidence and time trends of brain metastases admissions among breast cancer patients in Sweden. Br J Cancer 106(11):1850–1853. doi: 10.1038/bjc.2012.163bjc2012163 CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Lin NU, Winer EP (2007) Brain metastases: the HER2 paradigm. Clin Cancer Res 13(6):1648–1655. doi: 10.1158/1078-0432.CCR-06-2478 CrossRefPubMedGoogle Scholar
  4. 4.
    Brufsky AM, Mayer M, Rugo HS, Kaufman PA, Tan-Chiu E, Tripathy D, Tudor IC, Wang LI, Brammer MG, Shing M, Yood MU, Yardley DA (2011) Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res 17(14):4834–4843. doi: 10.1158/1078-0432.CCR-10-296217/14/4834 CrossRefPubMedGoogle Scholar
  5. 5.
    Crivellari D, Pagani O, Veronesi A, Lombardi D, Nole F, Thurlimann B, Hess D, Borner M, Bauer J, Martinelli G, Graffeo R, Sessa C, Goldhirsch A (2001) High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel. Ann Oncol 12(3):353–356CrossRefPubMedGoogle Scholar
  6. 6.
    Dawood S, Broglio K, Esteva FJ, Ibrahim NK, Kau SW, Islam R, Aldape KD, Yu TK, Hortobagyi GN, Gonzalez-Angulo AM (2008) Defining prognosis for women with breast cancer and CNS metastases by HER2 status. Ann Oncol 19(7):1242–1248. doi: 10.1093/annonc/mdn036mdn036 CrossRefPubMedGoogle Scholar
  7. 7.
    Pestalozzi BC, Holmes E, de Azambuja E, Metzger-Filho O, Hogge L, Scullion M, Lang I, Wardley A, Lichinitser M, Sanchez RI, Muller V, Dodwell D, Gelber RD, Piccart-Gebhart MJ, Cameron D (2013) CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01). Lancet Oncol 14(3):244–248. doi: 10.1016/S1470-2045(13)70017-2S1470-2045(13)70017-2 CrossRefPubMedGoogle Scholar
  8. 8.
    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(2):110–121. doi: 10.1016/j.critrevonc.2009.11.003S1040-8428(09)00227-3 CrossRefPubMedGoogle Scholar
  9. 9.
    Olson EM, Abdel-Rasoul M, Maly J, Wu CS, Lin NU, Shapiro CL (2013) Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab. Ann Oncol 24(6):1526–1533. doi: 10.1093/annonc/mdt036 CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Bendell JC, Domchek SM, Burstein HJ, Harris L, Younger J, Kuter I, Bunnell C, Rue M, Gelman R, Winer E (2003) Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97(12):2972–2977. doi: 10.1002/cncr.11436 CrossRefPubMedGoogle Scholar
  11. 11.
    DiStefano A, Yong Yap Y, Hortobagyi GN, Blumenschein GR (1979) The natural history of breast cancer patients with brain metastases. Cancer 44(5):1913–1918CrossRefPubMedGoogle Scholar
  12. 12.
    Engel J, Eckel R, Aydemir U, Aydemir S, Kerr J, Schlesinger-Raab A, Dirschedl P, Holzel D (2003) Determinants and prognoses of locoregional and distant progression in breast cancer. Int J Radiat Oncol Biol Phys 55(5):1186–1195CrossRefPubMedGoogle Scholar
  13. 13.
    Hall WA, Djalilian HR, Nussbaum ES, Cho KH (2000) Long-term survival with metastatic cancer to the brain. Med Oncol 17(4):279–286CrossRefPubMedGoogle Scholar
  14. 14.
    Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr (2004) Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 363(9422):1665–1672. doi: 10.1016/S0140-6736(04)16250-8S0140-6736(04)16250-8 CrossRefPubMedGoogle Scholar
  15. 15.
    Lin NU, Bellon JR, Winer EP (2004) CNS metastases in breast cancer. J Clin Oncol 22(17):3608–3617. doi: 10.1200/JCO.2004.01.17522/17/3608 CrossRefPubMedGoogle Scholar
  16. 16.
    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(3):311–317. doi: 10.1007/s11060-007-9420-5 CrossRefPubMedGoogle Scholar
  17. 17.
    Church DN, Modgil R, Guglani S, Bahl A, Hopkins K, Braybrooke JP, Blair P, Price CG (2008) Extended survival in women with brain metastases from HER2 overexpressing breast cancer. Am J Clin Oncol 31(3):250–254. doi: 10.1097/COC.0b013e31815a43c4 CrossRefPubMedGoogle Scholar
  18. 18.
    Yap YS, Cornelio GH, Devi BC, Khorprasert C, Kim SB, Kim TY, Lee SC, Park YH, Sohn JH, Sutandyo N, Wong DW, Kobayashi M, Landis SH, Yeoh EM, Moon H, Ro J (2012) Brain metastases in Asian HER2-positive breast cancer patients: anti-HER2 treatments and their impact on survival. Br J Cancer 107(7):1075–1082. doi: 10.1038/bjc.2012.346bjc2012346 CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Black PM, Johnson MD (2004) Surgical resection for patients with solid brain metastases: current status. J Neurooncol 69(1–3):119–124CrossRefPubMedGoogle Scholar
  20. 20.
    Alexander E 3rd, Moriarty TM, Davis RB, Wen PY, Fine HA, Black PM, Kooy HM, Loeffler JS (1995) Stereotactic radiosurgery for the definitive, noninvasive treatment of brain metastases. J Natl Cancer Inst 87(1):34–40CrossRefPubMedGoogle Scholar
  21. 21.
    Melisko ME, Moore DH, Sneed PK, De Franco J, Rugo HS (2008) Brain metastases in breast cancer: clinical and pathologic characteristics associated with improvements in survival. J Neurooncol 88(3):359–365. doi: 10.1007/s11060-008-9578-5 CrossRefPubMedGoogle Scholar
  22. 22.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752. doi: 10.1038/35021093 CrossRefPubMedGoogle Scholar
  23. 23.
    Metzger-Filho O, Sun Z, Viale G, Price KN, Crivellari D, Snyder RD, Gelber RD, Castiglione-Gertsch M, Coates AS, Goldhirsch A, Cardoso F (2013) Patterns of Recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX. J Clin Oncol 31(25):3083–3090. doi: 10.1200/JCO.2012.46.1574 CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Prat A, Perou CM (2011) Deconstructing the molecular portraits of breast cancer. Mol Oncol 5(1):5–23. doi: 10.1016/j.molonc.2010.11.003 CrossRefPubMedGoogle Scholar
  25. 25.
    Lobbezoo DJ, van Kampen RJ, Voogd AC, Dercksen MW, van den Berkmortel F, Smilde TJ, van de Wouw AJ, Peters FP, van Riel JM, Peters NA, de Boer M, Borm GF, Tjan-Heijnen VC (2013) Prognosis of metastatic breast cancer subtypes: the hormone receptor/HER2-positive subtype is associated with the most favorable outcome. Breast Cancer Res Treat 141(3):507–514. doi: 10.1007/s10549-013-2711-y CrossRefPubMedGoogle Scholar
  26. 26.
    Sperduto PW, Kased N, Roberge D, Chao ST, Shanley R, Luo X, Sneed PK, Suh J, Weil RJ, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M (2013) The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer. J Neurooncol 112(3):467–472. doi: 10.1007/s11060-013-1083-9 CrossRefPubMedGoogle Scholar
  27. 27.
    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(5):2111–2117. doi: 10.1016/j.ijrobp.2011.02.027 CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    The World Health Organization (1983) Histological typing of breast tumors. Neoplasma 30(1):113–123Google Scholar
  29. 29.
    Bloom HJ, Richardson WW (1957) Histological grading and prognosis in breast cancer; a study of 1,409 cases of which 359 have been followed for 15 years. Br J Cancer 11(3):359–377CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    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(4):419–425. doi: 10.1200/JCO.2011.38.0527 CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Miller KD, Weathers T, Haney LG, Timmerman R, Dickler M, Shen J, Sledge GW Jr (2003) Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival. Ann Oncol 14(7):1072–1077CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Naoki Niikura
    • 1
    • 2
    Email author
  • Naoki Hayashi
    • 3
  • Norikazu Masuda
    • 4
  • Seiki Takashima
    • 5
  • Rikiya Nakamura
    • 6
  • Ken-ichi Watanabe
    • 7
  • Chizuko Kanbayashi
    • 8
  • Mayumi Ishida
    • 9
  • Yasuo Hozumi
    • 10
  • Michiko Tsuneizumi
    • 11
  • Naoto Kondo
    • 12
  • Yoichi Naito
    • 13
    • 14
  • Yayoi Honda
    • 15
  • Akira Matsui
    • 16
  • Tomomi Fujisawa
    • 17
  • Risa Oshitanai
    • 1
  • Hiroyuki Yasojima
    • 4
  • Yutaka Tokuda
    • 1
  • Shigehira Saji
    • 2
  • Hiroji Iwata
    • 12
  1. 1.Department of Breast and Endocrine SurgeryTokai University School of MedicineIseharaJapan
  2. 2.Department of Target Therapy OncologyKyoto University Graduate School of MedicineKyotoJapan
  3. 3.Department of Breast Surgical OncologySt. Luke’s International HospitalTokyoJapan
  4. 4.Department of Surgery, Breast OncologyNational Hospital Organization Osaka National HospitalOsakaJapan
  5. 5.Department of Breast OncologyNational Hospital Organization Shikoku Cancer CenterMatsuyamaJapan
  6. 6.Chiba Cancer Center HospitalChibaJapan
  7. 7.Department of Breast SurgeryHokkaido Cancer CenterSapporoJapan
  8. 8.Department of Breast OncologyNiigata Cancer Center HospitalNiigataJapan
  9. 9.Department of Breast OncologyNational Kyushu Cancer CenterFukuokaJapan
  10. 10.Department of Breast OncologyJichi Medical UniversityShimotsukeJapan
  11. 11.Department of Breast SurgeryShizuoka General HospitalShizuokaJapan
  12. 12.Department of Breast OncologyAichi Cancer Center HospitalNagoyaJapan
  13. 13.Department of Experimental TherapeuticsNational Cancer Center Exploratory Oncology Research and Clinical Trial CenterTokyoJapan
  14. 14.Department of Breast and Medical OncologyNational Cancer Center Hospital EastChibaJapan
  15. 15.Division of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Disease CenterKomagome HospitalTokyoJapan
  16. 16.Department of Surgery, National Hospital OrganizationTokyo Medical CenterTokyoJapan
  17. 17.Gunma Prefectural Cancer CenterOtaJapan

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