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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Identification of breast cancer patients with a high risk of developing brain metastases: a single-institutional retrospective analysis

Authors: Volker Rudat, Hamdan El-Sweilmeen, Iris Brune-Erber, Alaa Ahmad Nour, Nidal Almasri, Saleh Altuwaijri, Elias Fadel

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

The objective of this study was to identify breast cancer patients with a high risk of developing brain metastases who may benefit from pre-emptive medical intervention.

Methods

Medical records of 352 breast cancer patients with local or locoregional disease at diagnosis were retrospectively analysed. The brain metastasis-free survival was estimated using the Kaplan-Meier method and patient groups were compared using the log rank test. The simultaneous relationship of multiple prognostic factors was assessed using Cox’s proportional hazard regression analysis. The Fisher exact test was used to test the difference of proportions for statistical significance.

Results

On univariate analysis, statistically highly significant unfavourable risk factors for the brain metastasis-free survival were negative ER status, negative PR status, and triple negative tumor subtype. Young age at diagnosis (≤35 years) and advanced disease stage were not statistically significant (p = 0.10). On multivariate analysis, the only independent significant factor was the ER status (negative ER status; hazard radio (95% confidence interval), 5.1 (1.8-14.6); p = 0.003). In the subgroup of 168 patients with a minimum follow-up of 24 months, 49 patients developed extracranial metastases as first metastatic event. Of those, 7 of 15 (46.6%) with a negative ER status developed brain metastases compared to 5 of 34 (14.7%) with a positive ER status (Fisher exact test, p = 0.03). The median time interval (minimum-maximum) between the diagnosis of extracranial and brain metastases was 7.5 months (1-30 months).

Conclusions

Breast cancer patients with extracranial metastasis and negative ER status exhibited an almost 50% risk of developing brain metastasis during their course of disease. Future studies are highly desired to evaluate the efficacy of pre-emptive medical intervention such as prophylactic treatment or diagnostic screening for high risk breast cancer patients.
Appendix
Available only for authorised users
Literature
1.
Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE: Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004, 22 (14): 2865-2872. 10.1200/JCO.2004.12.149.CrossRefPubMed
2.
Schouten LJ, Rutten J, Huveneers HA, Twijnstra A: Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002, 94 (10): 2698-2705. 10.1002/cncr.10541.CrossRefPubMed
3.
Tsukada Y, Fouad A, Pickren JW, Lane WW: Central nervous system metastasis from breast carcinoma. Autopsy study Cancer. 1983, 52 (12): 2349-2354.PubMed
4.
Lin NU, Bellon JR, Winer EP: CNS metastases in breast cancer. J Clin Oncol. 2004, 22 (17): 3608-3617. 10.1200/JCO.2004.01.175.CrossRefPubMed
5.
Lin NU, Winer EP: Brain metastases: the HER2 paradigm. Clin Cancer Res an official j Am Assoc Cancer Res. 2007, 13 (6): 1648-1655. 10.1158/1078-0432.CCR-06-2478.CrossRef
6.
Kiely BE, Soon YY, Tattersall MH, Stockler MR: How long have I got? Estimating typical, best-case, and worst-case scenarios for patients starting first-line chemotherapy for metastatic breast cancer: a systematic review of recent randomized trials. J Clin Oncol official j Am Soc Clinical Oncol. 2011, 29 (4): 456-463. 10.1200/JCO.2010.30.2174.CrossRef
7.
Larsen PB, Kumler I, Nielsen DL: A systematic review of trastuzumab and lapatinib in the treatment of women with brain metastases from HER2-positive breast cancer. Cancer Treatment Reviews. 2013, 39 (7): 720-727. 10.1016/j.ctrv.2013.01.006.CrossRefPubMed
8.
Tsao MN, Lloyd N, Wong RK, Chow E, Rakovitch E, Laperriere N, Xu W, Sahgal A: Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2012, 4, CD003869
9.
Fokstuen T, Wilking N, Rutqvist LE, Wolke J, Liedberg A, Signomklao T, Fernberg JO: Radiation therapy in the management of brain metastases from breast cancer. Breast Cancer Res Treat. 2000, 62 (3): 211-216. 10.1023/A:1006486423827.CrossRefPubMed
10.
Amendola BE, Wolf AL, Coy SR, Amendola M, Bloch L: Gamma knife radiosurgery in the treatment of patients with single and multiple brain metastases from carcinoma of the breast. Cancer j (Sudbury, Mass). 2000, 6 (2): 88-92.
11.
Lederman G, Wronski M, Fine M: Fractionated radiosurgery for brain metastases in 43 patients with breast carcinoma. Breast Cancer Res Treat. 2001, 65 (2): 145-154. 10.1023/A:1006490200335.CrossRefPubMed
12.
Matsunaga S, Shuto T, Kawahara N, Suenaga J, Inomori S, Fujino H: Gamma Knife surgery for metastatic brain tumors from primary breast cancer: treatment indication based on number of tumors and breast cancer phenotype. J Neurosurg. 2010, 113 (Suppl): 65-72.PubMed
13.
Wronski M, Arbit E, McCormick B: Surgical treatment of 70 patients with brain metastases from breast carcinoma. Cancer. 1997, 80 (9): 1746-1754. 10.1002/(SICI)1097-0142(19971101)80:9<1746::AID-CNCR8>3.0.CO;2-C.CrossRefPubMed
14.
Berghoff A, Bago-Horvath Z, De Vries C, Dubsky P, Pluschnig U, Rudas M, Rottenfusser A, Knauer M, Eiter H, Fitzal F, Dieckmann K, Mader RM, Gnant M, Zielinski CC, Steger GG, Preusser M, Bartsch R: Brain metastases free survival differs between breast cancer subtypes. Br J Cancer. 2012, 106 (3): 440-446. 10.1038/bjc.2011.597.CrossRefPubMedPubMedCentral
15.
Weil RJ, Palmieri DC, Bronder JL, Stark AM, Steeg PS: Breast cancer metastasis to the central nervous system. Am J Pathol. 2005, 167 (4): 913-920. 10.1016/S0002-9440(10)61180-7.CrossRefPubMedPubMedCentral
16.
Gonzalez-Angulo AM, Cristofanilli M, Strom EA, Buzdar AU, Kau SW, Broglio KR, Smith TL, Hortobagyi GN: Central nervous system metastases in patients with high-risk breast carcinoma after multimodality treatment. Cancer. 2004, 101 (8): 1760-1766. 10.1002/cncr.20530.CrossRefPubMed
17.
Evans AJ, James JJ, Cornford EJ, Chan SY, Burrell HC, Pinder SE, Gutteridge E, Robertson JF, Hornbuckle J, Cheung KL: Brain metastases from breast cancer: identification of a high-risk group. Clin Oncol (R Coll Radiol (G B)). 2004, 16 (5): 345-349. 10.1016/j.clon.2004.03.012.CrossRef
18.
Slimane K, Andre F, Delaloge S, Dunant A, Perez A, Grenier J, Massard C, Spielmann M: Risk factors for brain relapse in patients with metastatic breast cancer. Ann Oncol. 2004, 15 (11): 1640-1644. 10.1093/annonc/mdh432.CrossRefPubMed
19.
Albiges L, Andre F, Balleyguier C, Gomez-Abuin G, Chompret A, Delaloge S: Spectrum of breast cancer metastasis in BRCA1 mutation carriers: highly increased incidence of brain metastases. Ann Oncol official j Eur Soc Med Oncol/ESMO. 2005, 16 (11): 1846-1847. 10.1093/annonc/mdi351.CrossRef
20.
Rudat V, Alaradi AA, Mohamed A, Ai-Yahya K, Altuwaijri S: Tangential beam IMRT versus tangential beam 3D-CRT of the chest wall in postmastectomy breast cancer patients: a dosimetric comparison. Radiat Oncol (Lond, Engl). 2011, 6: 26-10.1186/1748-717X-6-26.CrossRef
21.
Harvey JM, Clark GM, Osborne CK, Allred DC: Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol official j Am Soc Clin Oncol. 1999, 17 (5): 1474-1481.
22.
Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007, 131 (1): 18-43.PubMed
23.
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, van de Rijn M, Perou CM: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004, 10 (16): 5367-5374. 10.1158/1078-0432.CCR-04-0220.CrossRefPubMed
24.
Abd El-Rehim DM, Ball G, Pinder SE, Rakha E, Paish C, Robertson JF, Macmillan D, Blamey RW, Ellis IO: High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int j cancer J int du cancer. 2005, 116 (3): 340-350. 10.1002/ijc.21004.CrossRef
25.
Abd El-Rehim DM, Pinder SE, Paish CE, Bell J, Blamey RW, Robertson JF, Nicholson RI, Ellis IO: Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol. 2004, 203 (2): 661-671. 10.1002/path.1559.CrossRefPubMed
26.
Brenton JD, Carey LA, Ahmed AA, Caldas C: Molecular classification and molecular forecasting of breast cancer: ready for clinical application?. J Clin Oncol official j Am Soc Clin Oncol. 2005, 23 (29): 7350-7360. 10.1200/JCO.2005.03.3845.CrossRef
27.
van de Rijn M, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J, Torhorst J, Sauter G, Zuber M, Kochli OR, Mross F, Dieterich H, Seitz R, Ross D, Botstein D, Brown P: Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol. 2002, 161 (6): 1991-1996. 10.1016/S0002-9440(10)64476-8.CrossRefPubMedPubMedCentral
28.
Tamimi RM, Baer HJ, Marotti J, Galan M, Galaburda L, Fu Y, Deitz AC, Connolly JL, Schnitt SJ, Colditz GA, Collins LC: Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer. Breast Cancer Res: BCR. 2008, 10 (4): R67-10.1186/bcr2128.CrossRefPubMedPubMedCentral
29.
Rudat V, Brune-Erbe I, Noureldin A, Bushnag Z, Almuraikhi N, Altuwaijri S: Epidemiology of breast cancer patients at a tertiary care center in the Eastern Province of Saudi Arabia. Gulf J Oncolog. 2012, 1 (11): 45-49.
30.
Rudat V, Birido N, Tuwaijri S, Al-Abbadi MA: Body Mass Index and Breast Cancer Risk: A Retrospective Multi-Institutional Analysis in Saudi Arabia. Adv Breast Cancer Res. 2013, 2 (1): 4-CrossRef
31.
Lee YT: Breast carcinoma: pattern of metastasis at autopsy. J Surg Oncol. 1983, 23 (3): 175-180. 10.1002/jso.2930230311.CrossRefPubMed
32.
Saip P, Cicin I, Eralp Y, Karagol H, Kucucuk S, Cosar Alas R, Yavuz E, Dincer M, Saglam E, Topuz E: Identification of patients who may benefit from the prophylactic cranial radiotherapy among breast cancer patients with brain metastasis. J Neuro-Oncol. 2009, 93 (2): 243-251. 10.1007/s11060-008-9769-0.CrossRef
33.
Blanchard P, Le Pechoux C: Prophylactic cranial irradiation in lung cancer. Curr Opin Oncol. 2010, 22 (2): 94-101. 10.1097/CCO.0b013e32833500ef.CrossRefPubMed
34.
Slotman BJ, Mauer ME, Bottomley A, Faivre-Finn C, Kramer GW, Rankin EM, Snee M, Hatton M, Postmus PE, Collette L, Senan S: Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international Phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups. J Clin Oncol: official jAm Soc Clin Oncol. 2009, 27 (1): 78-84.CrossRef
35.
Sun A, Bae K, Gore EM, Movsas B, Wong SJ, Meyers CA, Bonner JA, Schild SE, Gaspar LE, Bogart JA, Werner-Wasik M, Choy H: Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis. J Clin Oncol: official j Am Soc Clin Oncol. 2011, 29 (3): 279-286. 10.1200/JCO.2010.29.6053.CrossRef
36.
Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S: Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007, 357 (7): 664-672. 10.1056/NEJMoa071780.CrossRefPubMed
37.
Le Pechoux C, Dunant A, Senan S, Wolfson A, Quoix E, Faivre-Finn C, Ciuleanu T, Arriagada R, Jones R, Wanders R, Lerouge D, Laplanche A: Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol. 2009, 10 (5): 467-474. 10.1016/S1470-2045(09)70101-9.CrossRefPubMed
38.
Welzel G, Fleckenstein K, Schaefer J, Hermann B, Kraus-Tiefenbacher U, Mai SK, Wenz F: Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys. 2008, 72 (5): 1311-1318. 10.1016/j.ijrobp.2008.03.009.CrossRefPubMed
39.
Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE: A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008, 112 (3): 533-543. 10.1007/s10549-007-9885-0.CrossRefPubMed
40.
Bachelot T, Romieu G, Campone M, Dieras V, Cropet C, Dalenc F, Jimenez M, Le Rhun E, Pierga JY, Goncalves A, Leheurteur M, Domont J, Gutierrez M, Cure H, Ferrero JM, Labbe-Devilliers C: Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 2013, 14 (1): 64-71. 10.1016/S1470-2045(12)70432-1.CrossRefPubMed
41.
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: Characteristics of breast cancer patients with central nervous system metastases: a single-center experience. J Natl Med Assoc. 2008, 100 (5): 521-526.CrossRefPubMed
42.
Niwinska A, Tacikowska M, Murawska M: The effect of early detection of occult brain metastases in HER2-positive breast cancer patients on survival and cause of death. Int J Radiat Oncol Biol Phys. 2010, 77 (4): 1134-1139. 10.1016/j.ijrobp.2009.06.030.CrossRefPubMed
43.
Tomasevic ZI, Rakocevic Z, Tomasevic ZM, Milovanovic Z, Inic M, Kolarevic D, Lukic V, Kovac Z: Incidence of brain metastases in early stage HER2 3+ breast cancer patients; is there a role for brain CT in asymptomatic patients?. J BUON: official j Balkan Union of Oncol. 2012, 17 (2): 249-253.
44.
Vern-Gross TZ, Lawrence JA, Case LD, McMullen KP, Bourland JD, Metheny-Barlow LJ, Ellis TL, Tatter SB, Shaw EG, Urbanic JJ, Chan MD: Breast cancer subtype affects patterns of failure of brain metastases after treatment with stereotactic radiosurgery. J Neuro-Oncol. 2012, 110 (3): 381-388. 10.1007/s11060-012-0976-3.CrossRef
45.
Saunus JM, Momeny M, Simpson PT, Lakhani SR, Da Silva L: Molecular aspects of breast cancer metastasis to the brain. Genet res int. 2011, 2011: 219189-PubMedPubMedCentral
Metadata
Title
Identification of breast cancer patients with a high risk of developing brain metastases: a single-institutional retrospective analysis
Authors
Volker Rudat
Hamdan El-Sweilmeen
Iris Brune-Erber
Alaa Ahmad Nour
Nidal Almasri
Saleh Altuwaijri
Elias Fadel
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-289

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue

Research article

Prognostic influence of cyclooxygenase-2 protein and mRNA expression in node-negative breast cancer patients

Case report

Sunitinib-induced severe toxicities in a Japanese patient with the ABCG2 421 AA genotype

Research article

Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

Research article

Distress, anxiety and depression in patients with brain metastases before and after radiotherapy

Research article

Men’s knowledge and attitudes towards dietary prevention of a prostate cancer diagnosis: a qualitative study

Research article

Anti-cancer effect and gene modulation of ET-743 in human biliary tract carcinoma preclinical models
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits