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Erschienen in: Neurosurgical Review 3/2013

01.07.2013 | Original Article

The shifting landscape of metastatic breast cancer to the CNS

verfasst von: Matthew R. Quigley, Olivia Fukui, Brandon Chew, Sanjay Bhatia, Steven Karlovits

Erschienen in: Neurosurgical Review | Ausgabe 3/2013

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Abstract

The improved survival following the diagnosis of breast cancer has potentially altered the characteristics and course of patients presenting with CNS involvement. We therefore sought to define our current cohort of breast cancer patients with metastatic disease to the CNS in regard to modern biomarkers and clinical outcome. Review of clinical and radiographic records of women presenting to a tertiary medical center with the new diagnosis of CNS metastatic disease from breast cancer. This was a retrospective review from patients identities obtained from two prospective databases. There were 88 women analyzed who were treated over the period of January 2003 to February 2010, average age 56.9 years. At the time of initial presentation of CNS disease, 68 % of patients had multiple brain metastases, 17 % had a solitary metastasis, and 15 % had only leptomeningeal disease (LMD). The median survival for all patients from the time of diagnosis of breast disease was 50.0 months, and 9.7 months from diagnosis of CNS involvement. The only factor related to overall survival was estrogen receptor-positive pathology (57.6 v. 38.2 months, p = .02 log-rank); those related to survival post CNS diagnosis were presentation with LMD (p = .004, HR = 3.1, Cox regression) and triple-negative hormonal/HER2 status (p = .02, HR = 2.3, Cox regression). Patients with either had a median survival of 3.1 months (no patients in common). Of the 75 patients who initially presented with metastatic brain lesions, 20 (26 %) subsequently developed LMD in the course of their disease (median 10.4 months), following which survival was grim (1.8 months median). Symptoms of LMD were most commonly lower extremity weakness (14/33), followed by cranial nerve deficits (11/33). The recently described Graded Prognostic Assessment (GPA) tumor index stratified median survival at 2.5, 5.9, 13.1, and 21.7 months, respectively, for indices of 1–4 (p = .004, log-rank), which contrasted with the nonsignificant survival difference between Radiation Therapy Oncology Group Recursive Partitioning Analysis classes one and two. (13.1 v. 13.2, p = .8, log-rank). Treatment of patients with metastatic brain disease from breast cancer should be tailored to the patient’s hormonal status and GPA index. Practitioners must be vigilant for the development of LMD, especially as it often presents with nondescript complaints such as back pain.
Literatur
1.
Zurück zum Zitat Altundag K, Bondy ML, Mirza NQ, Shu-Wan K, Brogilo K, Hortobagyl GN, Rivera E (2007) Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis. Cancer 110:2640–2647CrossRefPubMed Altundag K, Bondy ML, Mirza NQ, Shu-Wan K, Brogilo K, Hortobagyl GN, Rivera E (2007) Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis. Cancer 110:2640–2647CrossRefPubMed
2.
Zurück zum Zitat Bindal AK, Bindal RK, Hess KR, Shiu A, Hassenbusch SJ, Shi WM, Sawaya R (1996) Surgery versus radiosurgery in the treatment of brain metastasis. J Neurosurg 84:748–754CrossRefPubMed Bindal AK, Bindal RK, Hess KR, Shiu A, Hassenbusch SJ, Shi WM, Sawaya R (1996) Surgery versus radiosurgery in the treatment of brain metastasis. J Neurosurg 84:748–754CrossRefPubMed
3.
Zurück zum Zitat Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC (2006) Race, breast cancer subtypes and survival in the Carolina Breast Cancer Study. JAMA 295(295):2492–2502CrossRefPubMed Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC (2006) Race, breast cancer subtypes and survival in the Carolina Breast Cancer Study. JAMA 295(295):2492–2502CrossRefPubMed
5.
Zurück zum Zitat Cho SY, Choi HY (1980) Causes of death and metastatic patterns in patients with mammary cancer. Am J Clin Pathol 73:232–234PubMed Cho SY, Choi HY (1980) Causes of death and metastatic patterns in patients with mammary cancer. Am J Clin Pathol 73:232–234PubMed
6.
Zurück zum Zitat Clarke JL, Perez HR, Jacks LM, Panageas KS, DeAngelis LM (2010) Leptomeningeal metastases in the MRI era. Neurology 74:1449–1454CrossRefPubMed Clarke JL, Perez HR, Jacks LM, Panageas KS, DeAngelis LM (2010) Leptomeningeal metastases in the MRI era. Neurology 74:1449–1454CrossRefPubMed
7.
Zurück zum Zitat Dawood S, Gonzalez-Angulo AM, Alabarracin C, Yu TK, Hortobagyl GN, Buchholz TA, Woodward WA (2010) Prognostic factors of survival in the trastuzumab era among women with breast cancer and brain metastases who receive whole brain radiotherapy. Cancer 116:3084–3092CrossRefPubMed Dawood S, Gonzalez-Angulo AM, Alabarracin C, Yu TK, Hortobagyl GN, Buchholz TA, Woodward WA (2010) Prognostic factors of survival in the trastuzumab era among women with breast cancer and brain metastases who receive whole brain radiotherapy. Cancer 116:3084–3092CrossRefPubMed
8.
Zurück zum Zitat Dowsett M, Dubier AK (2008) Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin Cancer Res 14:8019–8026CrossRefPubMed Dowsett M, Dubier AK (2008) Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin Cancer Res 14:8019–8026CrossRefPubMed
9.
Zurück zum Zitat Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365:1687–1717CrossRef Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365:1687–1717CrossRef
10.
Zurück zum Zitat Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMed
11.
Zurück zum Zitat Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R (1997) Recursive partitioning (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751CrossRefPubMed Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R (1997) Recursive partitioning (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751CrossRefPubMed
12.
Zurück zum Zitat Gauthier H, Guilhaume MN, Bidard FC, Pierga JY, Girre V, Cottu PH, Laurence V, Livartowski A, Mignot L, Diéras V (2010) Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol 21:2183–2187CrossRefPubMed Gauthier H, Guilhaume MN, Bidard FC, Pierga JY, Girre V, Cottu PH, Laurence V, Livartowski A, Mignot L, Diéras V (2010) Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol 21:2183–2187CrossRefPubMed
13.
Zurück zum Zitat Harputluoglu H, Dizdar O, Aksoy S, Kilickap S, Dede DS, Ozisik Y, Guler N, Barista I, Gullu I, Hayran M, Selek U, Cengiz M, Zorlu F, Tekuzman G, Altundag K (2008) Characteristics of breast cancer patients with central nervous system metastases: a single center experience. J Nat Med Assoc 100:521–526 Harputluoglu H, Dizdar O, Aksoy S, Kilickap S, Dede DS, Ozisik Y, Guler N, Barista I, Gullu I, Hayran M, Selek U, Cengiz M, Zorlu F, Tekuzman G, Altundag K (2008) Characteristics of breast cancer patients with central nervous system metastases: a single center experience. J Nat Med Assoc 100:521–526
14.
Zurück zum Zitat Hicks DG, Short SM, Prescott NL, Tarr SM, Coleman KA, Yoder BJ, Crowe JP, Choueiri TK, Dawson AE, Budd GT, Tubbs RR, Casey G, Weil RJ (2006) Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin CK5/6, and overexpress HER2 or EGFR. Am J Surg Pathol 30:1097–1104CrossRefPubMed Hicks DG, Short SM, Prescott NL, Tarr SM, Coleman KA, Yoder BJ, Crowe JP, Choueiri TK, Dawson AE, Budd GT, Tubbs RR, Casey G, Weil RJ (2006) Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin CK5/6, and overexpress HER2 or EGFR. Am J Surg Pathol 30:1097–1104CrossRefPubMed
15.
Zurück zum Zitat Kaplan IW, Meier R (1959) Submucous lipoma of the colon. Am J Gastroenterol 31:673–683PubMed Kaplan IW, Meier R (1959) Submucous lipoma of the colon. Am J Gastroenterol 31:673–683PubMed
16.
Zurück zum Zitat Karlovits BJ, Quigley MR, Karlovits SM, Miller L, Johnson M, Gayou O, Fuhrer R (2009) Stereotactic radiosurgery boost to the resection bed for oligometastatic brain disease: challenging the tradition of adjuvant whole-brain radiotherapy. Neurosurg Focus 27(6):E7CrossRefPubMed Karlovits BJ, Quigley MR, Karlovits SM, Miller L, Johnson M, Gayou O, Fuhrer R (2009) Stereotactic radiosurgery boost to the resection bed for oligometastatic brain disease: challenging the tradition of adjuvant whole-brain radiotherapy. Neurosurg Focus 27(6):E7CrossRefPubMed
17.
Zurück zum Zitat 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 Neuro-Onc 106:303–313CrossRef 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 Neuro-Onc 106:303–313CrossRef
18.
Zurück zum Zitat Lee SS, Ahn J, Kim MK, Sym SJ, Gong G, Ahn AD, Kim S, Kim WK (2008) Brain metastases in breast cancer: prognostic factors and management. Breast Cancer Res Treat 111:523–530CrossRefPubMed Lee SS, Ahn J, Kim MK, Sym SJ, Gong G, Ahn AD, Kim S, Kim WK (2008) Brain metastases in breast cancer: prognostic factors and management. Breast Cancer Res Treat 111:523–530CrossRefPubMed
19.
20.
Zurück zum Zitat Lin NU, Bellon JR, Winer EP (2004) CNS metastases in breast cancer. J Clin Oncol 22:3609–3617 Lin NU, Bellon JR, Winer EP (2004) CNS metastases in breast cancer. J Clin Oncol 22:3609–3617
21.
Zurück zum Zitat Lin NU, Claus E, Sohl J, Razzak AR, Arnaout A, Winer EP (2008) Sites of distant relapse and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases. Cancer 113:2638–2645CrossRefPubMed Lin NU, Claus E, Sohl J, Razzak AR, Arnaout A, Winer EP (2008) Sites of distant relapse and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases. Cancer 113:2638–2645CrossRefPubMed
22.
Zurück zum Zitat Nam B, Kim S, Han H, Kwon Y, Lee KS, Kim TH, Ro J (2008) Breast cancer subtypes and survival in patients with brain metastases. Breast Cancer Res 10:R20CrossRefPubMed Nam B, Kim S, Han H, Kwon Y, Lee KS, Kim TH, Ro J (2008) Breast cancer subtypes and survival in patients with brain metastases. Breast Cancer Res 10:R20CrossRefPubMed
23.
Zurück zum Zitat Oakman C, Viale G, DiLeo A (2010) Management of triple negative breast cancer. Breast 19:312–321CrossRefPubMed Oakman C, Viale G, DiLeo A (2010) Management of triple negative breast cancer. Breast 19:312–321CrossRefPubMed
24.
Zurück zum Zitat Patanaphan V, Salazar OM, Risco R (1988) Breast cancer: metastatic patterns and their prognosis. South Med J 81:1109–1112CrossRefPubMed Patanaphan V, Salazar OM, Risco R (1988) Breast cancer: metastatic patterns and their prognosis. South Med J 81:1109–1112CrossRefPubMed
25.
Zurück zum Zitat Paek SH, Audu PB, Sperling MR, Cho J, Andrews DW (2005) Reevaluation of surgery for the treatment of brain metastases: review of 208 patients with single or multiple brain metastases treated at one institution with modern neurosurgical techniques. Neurosurgery 56:1021–1034PubMed Paek SH, Audu PB, Sperling MR, Cho J, Andrews DW (2005) Reevaluation of surgery for the treatment of brain metastases: review of 208 patients with single or multiple brain metastases treated at one institution with modern neurosurgical techniques. Neurosurgery 56:1021–1034PubMed
26.
Zurück zum Zitat Perou CM, Sørlie 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, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752CrossRefPubMed Perou CM, Sørlie 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, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752CrossRefPubMed
27.
Zurück zum Zitat Peto R, Boreham J, Clarke M, Davies C, Beral V (2000) UK and USA breast cancer deaths down 25 % in year 2000 at ages 20–69 years. Lancet 355:1822CrossRefPubMed Peto R, Boreham J, Clarke M, Davies C, Beral V (2000) UK and USA breast cancer deaths down 25 % in year 2000 at ages 20–69 years. Lancet 355:1822CrossRefPubMed
28.
Zurück zum Zitat Quigley MR, Fuhrer R, Karlovits S, Karlovits B, Johnson M (2008) Single session stereotactic radiosurgery boost to the post-operative site in lieu of whole brain radiation in metastatic brain disease. J Neurooncol 87:327–332CrossRefPubMed Quigley MR, Fuhrer R, Karlovits S, Karlovits B, Johnson M (2008) Single session stereotactic radiosurgery boost to the post-operative site in lieu of whole brain radiation in metastatic brain disease. J Neurooncol 87:327–332CrossRefPubMed
29.
Zurück zum Zitat Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lønning P, Børresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. PNAS 98:10869–10874CrossRefPubMed Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lønning P, Børresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. PNAS 98:10869–10874CrossRefPubMed
30.
Zurück zum Zitat Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lønning PE, Brown PO, Børresen-Dale AL, Botstein D (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. PNAS 100:8418–8423CrossRefPubMed Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lønning PE, Brown PO, Børresen-Dale AL, Botstein D (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. PNAS 100:8418–8423CrossRefPubMed
31.
Zurück zum Zitat 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 (2011) 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):2111–2117CrossRefPubMed 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 (2011) 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):2111–2117CrossRefPubMed
32.
Zurück zum Zitat Tsukada Y, Fouad A, Pickeren JW, Lane WW (1983) Central nervous system metastasis from breast carcinoma. Cancer 52:2349–2354CrossRefPubMed Tsukada Y, Fouad A, Pickeren JW, Lane WW (1983) Central nervous system metastasis from breast carcinoma. Cancer 52:2349–2354CrossRefPubMed
Metadaten
Titel
The shifting landscape of metastatic breast cancer to the CNS
verfasst von
Matthew R. Quigley
Olivia Fukui
Brandon Chew
Sanjay Bhatia
Steven Karlovits
Publikationsdatum
01.07.2013
Verlag
Springer-Verlag
Erschienen in
Neurosurgical Review / Ausgabe 3/2013
Print ISSN: 0344-5607
Elektronische ISSN: 1437-2320
DOI
https://doi.org/10.1007/s10143-012-0446-6

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