Treatment outcomes and prognostic factors for patients with brain metastases from breast cancer of each subtype: a multicenter retrospective analysis
- 1k Downloads
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.
KeywordsBreast cancer Brain metastases Retrospective analysis Subtype
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.
There are no conflicts of interest to declare.
- 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
- 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.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
- 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.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.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.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
- 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
- 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
- 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
- 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.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
- 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.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.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.The World Health Organization (1983) Histological typing of breast tumors. Neoplasma 30(1):113–123Google Scholar
- 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