Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Neuro-Oncology
Published in: Journal of Neuro-Oncology 1/2014

01-03-2014 | Clinical Study

CSF CA 15-3 in breast cancer-related leptomeningeal metastases

Authors: Emilie Le Rhun, Andrew Kramar, Sophie Salingue, Marie Girot, Isabelle Rodrigues, Audrey Mailliez, Fahed Zairi, Edgar Bakhache, Yves Marie Robin, Sophie Taillibert, François Dubois, Jacques Bonneterre, Marc C. Chamberlain

Published in: Journal of Neuro-Oncology | Issue 1/2014

Login to get access

Abstract

The sensitivity of CSF cytology, the standard method for diagnosis of leptomeningeal metastases (LM), is low. Serum cancer antigen 15-3 (CA 15-3) is frequently used for the monitoring of patients with breast cancer (BC) and is a laboratory test available in most centers. The aim of the current study was to determine the feasibility of measuring CSF CA 15-3 and CA 15-3 CSF/serum ratio in patients with BC-related LM. Serum and CSF CA 15-3 values were evaluated in 20 BC patients with LM (Group 1), 20 patients with LM from other primary cancers (Group 2), 20 BC patients with parenchymal brain metastases only (Group 3) and 20 controls (Group 4). CSF and serum were collected on the same day. Serum and CSF CA 15-3 were assessed by an automatized immuno-enzymatic technology (TRACE® technology, KRYPTOR Automate, Brahms Society, France). In univariate analysis, BC patients with LM (Group 1) compared to other groups, a significantly elevated serum CA 15-3 (median 51 U/ml, range 12–2819) and CSF CA 15-3 (median 8.7 U/ml, range 0.1–251) was observed. Additionally, the CSF/serum ratio of CA 15-3 was significantly higher in this group of patients (median 0.18, range 0.002–4.40). Multivariate analysis identified a cut-off for CSF CA15-3 with 80 % sensitivity and 70 % specificity. Conclusions: The current study confirms the feasibility of determining CSF CA 15-3 using a widely available technology. Evaluation of the CSF CA 15-3 may be useful in the diagnosis and management of BC-related LM but further studies are needed.
Literature
1.
de Azevedo CR, Cruz MR, Chinen LT, Peres SV, Peterlevitz MA, de Azevedo Pereira AE, Fanelli MF, Gimenes DL (2011) Meningeal carcinomatosis in breast cancer: prognostic factors and outcomes. J Neurooncol 104(2):565–572PubMedCrossRef
2.
Rudnika H, Niwinska A, Murawska M (2007) Breast cancer leptomeningeal metastasis - the role of a multimodality treatment. J Neurooncol 84:57–62CrossRef
3.
Clatot F, Philippin-Lauridant G, Ouvrier O, Nakry T, laberge-Le-Couteulx S, Guillemet C, Veyret C, Blot E (2009) Clinical improvement and survival in breast cancer leptomeningeal metastasis correlate with the cytologic response to intrathecal chemotherapy. J Neurooncol 95:421–426
4.
Gauthier H, Guilhaume MN, 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 21:2183–2187PubMedCrossRef
5.
Lee S, Ahn HK, Nam do H, Lee JI, Park W, Choi DH, Huh SJ, Park KT, Ahn JS, Im YH (2011) Leptomeningeal metastases from breast cancer: intrinsic subtypes may affect unique clinical manifestations. Breast Cancer Res Treat 129(3):809–817
6.
Le Rhun E, Taillibert S, Zairi F, Kotecki N, Devos P, Mailliez A, Servent V, Vanlemmens L, Vennin P, Boulanger T, Baranzelli MC, André C, Marliot G, Cazin JL, Dubois F, Assaker R, Bonneterre J, Chamberlain MC (2013) A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer. J Neurooncol 113(1):83–92PubMedCrossRef
7.
Lara-Medina F, Crismatt A, Villarreal-Garza C, Alvarado-Miranda A, Flores-Hernández L, González-Pinedo M, Gamboa-Vignolle C, Ruiz-González JD, Arrieta O (2012) Clinical features and prognostic factors in patients with carcinomatous meningitis secondary to breast cancer. Breast J 18(3):233–241PubMedCrossRef
8.
Meattini I, Livi L, Saieva C, Franceschini D, Marrazzo L, Greto D, Scotti V, Scoccianti S, Paiar F, Bordi L, Nori J, Sanchez L, Orzalesi L, Bianchi S, Biti G (2012) Prognostic factors and clinical features in patients with leptomeningeal metastases from breast cancer: a single center experience. J Chemother 24(5):279–284PubMedCrossRef
9.
Regierer AC, Stroux A, Kühnardt D, Dieing A, Lehenbauer-Dehm S, Flath B, Possinger K, Eucker J (2008) Contrast-enhancing meningeal lesions are associated with longer survival in breast cancer related leptomeningeal metastasis. Breast Care 3(2):118–123PubMedCentralPubMedCrossRef
10.
Jaeckle KA, Phuphanich S, Bent MJ, Aiken R, Batchelor T, Campbell T, Fulton D, Gilbert M, Heros D, Rogers L, O’Day SJ, Akerley W, Allen J, Baidas S, Gerlier SZ, Greenberg HS, LaFollette S, Lesser G, Mason W, Recht L, Wong E, Chamberlain MC, Cphn A, Glantz MJ, Gutheil JC, Maria B, Moots P, New P, Russel C, Shapiro W, Swinnen L, Howell SB (2001) Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabrine. Br J Cancer 84:157–163PubMedCentralPubMedCrossRef
11.
12.
Brem SS, Bierman PJ, Black P, Blumenthal DT, Brem H, Chamberlain MC, Chiocca EA, DeAngelis LM, Fenstermaker RA, Fine HA, Friedman A, Glass J, Grossman SA, Heimberger AB, Junck L, Levin V, Loeffler JJ, Maor MH, Narayana A, Newton HB, olivi A, Portnow J, Prados M, Raizer JJ, Rosenfeld SS, Shrieve DC, Stills AK Jr, Spence AM, Vrionis FD, National Comprehensive Cancer Network (2005) Central nervous system cancers: clinical practice guidelines in oncology. J Natl Compr Canc Netw 3:644–690
13.
Glass JP, Melamed M, Chernik NL, Posner JB (1979) Malignant cells in cerebrospinal fluid (CSF): the meaning of a positive CSF cytology. Neurology 29:1369–1375PubMedCrossRef
14.
Chamberlain MC, Glantz M, Groves MD, Wilson WH (2009) Diagnostic tools for neoplastic meningitis: detecting disease, identifying patient risk and determining benefit of treatment. Semin Oncol 36:S35–S45PubMedCrossRef
15.
Glantz MJ, Cole BF, Cobb J, Mills P, Lekos A, Walters BC, Recht LD (1998) Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer 82:733–739PubMedCrossRef
16.
Weston CL, Glantz MJ, Connor JR (2011) Detection of cancer cells in the cerebrospinal fluid: current methods and future directions. Fluids Barriers CNS 8:14PubMedCentralPubMedCrossRef
17.
Walbert T, Groves MD (2010) Known and emerging biomarkers of leptomeningeal metastasis and its response to treatment. Future Oncol 6:287–297PubMedCrossRef
18.
Corsini E, Bernardi G, Gaviani P, Silvani A, de Grazia U, Ciusani E, Croci D, Salmaggi A (2009) Intrathecal synthesis of tumor markers is a highly sensitive test in the diagnosis of leptomeningeal metastasis from solid cancers. Clin Chem Lab Med 47:874–879
19.
Herrlinger U, Fösrschier H, Küker W, Meyermann R, Bamberg M, Dichgns J and Weller: M (2004) Leptomeningeal metastasis: survival and prognosis in 155 patients. J Neurol Sci 223(2):167–178
20.
Reijneveld JC, Brandsma D, Boogerd W, Bonfrer JG, Kalmijn S, Voest EE, Geurts-Moespot A, Visser MC, Taphoorn MJ (2005) CSF levels of angiogenesis-related proteins in patients with leptomeningeal metastases. Neurology 65(7):1120–1122PubMedCrossRef
21.
van de Langerijt B, Gijtenbeek JM, de Reus HP, Sweep FC, Geurts-Moespot A, Hendriks JC, Kappelle AC, Verbeek MM (2006) CSF levels of growth factors and plasminogen activators in leptomeningeal metastases. Neurology 67(1):114–119PubMedCrossRef
22.
Groves M, Hess PVK, Colman H, Conrad CA, Gilbert MR, Weinberg J, Cristofanilli Yung WK, Liu TJ (2009) Biomarkers of disease: cerebrospinal fluid vascular endothelial growth factor (VEGF) and stromal cell derived factor (SDF)-1 levels in patients with neoplastic meningitis (NM) due to breast cancer, lung cancer and melanoma. J Neurooncol 94:229–234PubMedCrossRef
23.
Patel AS, Allen JE, Dicker DT, Peters KL, Sheehan JM, Glantz MJ, El-Deiry WS (2011) Identification and enumeration of circulating tumor cells in the cerebrospinal fluid of breast cancer patients with central nervous system metastases. Oncotarget 2:752–760PubMed
24.
Le Rhun E, Tu Q, De Carvalho Bittencourt M, Farre I, Mortier L, Cai H, Kohler C, Faure GC (2013) Detection and quantification of CSF malignant cells by the cell search technology in patients with melanoma leptomeningeal metastasis. Med Oncol 30(2):538
25.
Nayak L, Fleisher M, Gonzalez-Espinoza R, Lin O, Panageas K, Reiner A, Liu CM, Deangelis LM, Omuro A (2013) Rare cell capture technology for the diagnosis of leptomeningeal metastasis in solid tumors. Neurology 80(17):1598–1605PubMedCrossRef
26.
Römpp A, Dekker L, Taban I, Jenster G, Boogerd W, Bonfrer H, Spengler B, Heeren R, Smitt PS, Luider TM (2007) Identification of leptomeningeal metastasis-related proteins in cerebro-spinal fluid of patients with breast cancer by a combination of MALDI-TOF, MALDI-FTICR and nano LC-FTICR MS. Proteomics 7:474–481PubMedCrossRef
27.
Dekker LJ, Boogerd W, Stockhammer G, Dalebout JC, Siccama I, Zheng P, Bonfrer JM, Verschuuren JJ, Jenster G, Verbeek MM, Luider TM, Smitt PA (2005) MALDI-TOF mass spectrometry analysis of cerebrospinal fluid tryptic peptide profiles to diagnose leptomeningeal metastases in patients with breast cancer. Mol Cell Proteomics 4(9):1341–1349PubMedCrossRef
28.
Brandsma D, Voest EE, de Jager W, Bonfrer H, Algra A, Boogerd W, Korse T, Reijneveld JC, Verbeek MM, Rijkers G, Taphoorn MJ (2006) CSF protein profiling using multiplex immuno-assay: a potential new diagnostic tool for leptomeningeal metastases. J Neurol 253(9):1177–1784PubMedCrossRef
29.
Boogerd W, Vroom TM, van Heerde P, Brutel de la Rivière G, Peterse JL, van der Sande JJ (1988) CSF cytology versus immunocytochemistry in meningeal carcinomatosis. J Neurol Neurosurg Psychiatry. 51(1):142–145
30.
Bougel S, Lhermitte B, Gallagher G, de Flaugergues JC, Janzer RC, Benhattar J (2013) Methylation of the hTERT promoter: a novel cancer biomarker for leptomeningeal metastasis detection in cerebrospinal fluids. Clin Cancer Res 19(8):2216–2223PubMedCrossRef
31.
Sturgeon CM, Duffy MJ, Stenman UH, Lilja H, Brünner N, Chan DW, babain R, Bast RC Jr, Dowell B, Esteva FJ, Haglund C, Harbeck N, Hayes DF, Hotlen-Andersen M, Klee GG, Lamerz R, Looijenga LH, Molina R, Nielsen HJ, Rittenhouse H, Semjonow A, Shih leM, Sibley P, Sölétormos G, Stephan C, Sokoll L, Hoffman BR, Diamandis EP; National Academy of Clinical Biochemistry (2008) National academy of clinical biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem 54:11–79
32.
Bidart JM, Thuillier F, Augereau C, Chalas J, Daver A, Jacob N, Labrousse F, Voltot H (1999) Kinetics of serum tumor marker concentrations and usefulness in clinical monitoring. Clin Chem 45:1695–1707PubMed
33.
Martin PM (2007) Bilan et recommandations pour l’utilisation des marqueurs tumoraux sériques dans le cadre des cancers du sein en 2007 (French). In: Cancer du sein: Compte-rendu du cours supérieur francophone de cancérologie de Saint-Paul-de Vence, 18–20 janvier 2007. Springe, New York, pp 197–202
34.
Vassault A, Grafmeyer D, Naudin C, Dumont G, Bailly M, Henry J, Gerhardt MF (1986) Protocole de validation des techniques (document B) (French). Ann Biol Clin (Paris) 44:686–745
35.
Gauchez AS, Pez E, Boutonnat J, Bourre JC, Pelletier L, Payan R, Mousseau M (2007) Early detection of leptomeningeal metastasis in patients with metastatic breast carcinoma: validation of CA 15-3 measurement in cerebrospinal fluid (French). Ann Biol Clin (Paris) 65(6):653–658
36.
Bidard FC, Hajage D, Bachelot T, Delaloge S, Brain E, Campone M, Cottu P, Beuzeboc P, Rolland E, Mathiot C, Pierga JY (2012) Assessment of circulating tumor cells and serum markers for progression-free survival prediction in metastatic breast cancer: a prospective observational study. Breast Cancer Res 14(1):R29PubMedCentralPubMed
37.
38.
Kang SJ, Kim KS, Ha YS, Huh SY, Lee JH, Kim JK, Kim MJ (2010) Diagnostic value of cerebrospinal fluid level of carcinoembryonic antigen in patients with leptomeningeal carcinomatous metastasis. J Clin Neurol 6(1):33–37PubMedCentralPubMedCrossRef
39.
40.
DeAngelis LM (1988) Current diagnosis and treatment of leptomeningeal metastasis. J Neurooncol 38(2–3):245–252
Metadata
Title
CSF CA 15-3 in breast cancer-related leptomeningeal metastases
Authors
Emilie Le Rhun
Andrew Kramar
Sophie Salingue
Marie Girot
Isabelle Rodrigues
Audrey Mailliez
Fahed Zairi
Edgar Bakhache
Yves Marie Robin
Sophie Taillibert
François Dubois
Jacques Bonneterre
Marc C. Chamberlain
Publication date
01-03-2014
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2014
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-014-1361-1

Other articles of this Issue 1/2014

Journal of Neuro-Oncology 1/2014 Go to the issue

Clinical Study

Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression

Topic Review

Personal health records as portal to the electronic medical record

Letter to the Editor

The Neutrophil Lymphocyte Ratio in Patients with Glioblastoma Multiforme

Clinical Study

Neoadjuvant cisplatin plus temozolomide versus standard treatment in patients with unresectable glioblastoma or anaplastic astrocytoma: a differential effect of MGMT methylation

Clinical Study

Diffusion-weighted MRI derived apparent diffusion coefficient identifies prognostically distinct subgroups of pediatric diffuse intrinsic pontine glioma

Laboratory Investigation

C-terminally truncated form of αB-crystallin is associated with IDH1 R132H mutation in anaplastic astrocytoma