Abstract
Purpose
Discordances between the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), expression between primary breast tumors and their subsequent brain metastases (BM) were investigated in breast cancer patients.
Methods
We collected retrospective data from 11 institutions in 8 countries in a predefined-standardized format. Receptor status (positive or negative) was determined according to institutional guidelines (immunohistochemically and/or fluorescence in situ hybridization). The study was subject to each institution’s ethical research committee.
Results
A total of 167 breast cancer patients with BM were included. 25 patients out of 129 with a complete receptor information from both primary tumor and BM (ER, PR, HER2) available, had a change in receptor status: 7 of 26 (27%) ER/PR-positive/HER2-negative primaries (3 gained HER2; 4 lost expression of ER/PR); 10 of 31 (32%) ER/PR-positive/HER2-positive primaries (4 lost ER/PR only; 3 lost HER2 only; 3 lost both ER/PR and HER2); one of 33 (3%) ER/PR-negative receptor/HER2-positive primaries (gained ER); and 7 of 39 (18%) triple-negative primaries (5 gained ER/PR and 2 gained HER2).
Conclusions
The majority of breast cancer patients with BM in this series had primary HER2-enriched tumors, followed by those with a triple-negative profile. One out of 5 patients had a receptor discrepancy between the primary tumor and subsequent BM. Therefore, we advise receptor status assessment of BM in all breast cancer patients with available histology as it may have significant implications for therapy.
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References
Fox BD, Cheung VJ, Patel AJ, Suki D, Rao G (2011) Epidemiology of metastatic brain tumors. Neurosurg Clin N Am 22(1):1–6 v
Yonemori K, Tsuta K, Shimizu C, Hatanaka Y, Hashizume K, Ono M, Nakanishi Y, Hasegawa T, Miyakita Y, Narita Y et al (2008) Immunohistochemical profiles of brain metastases from breast cancer. J Neurooncol 90(2):223–228
Graesslin O, Abdulkarim BS, Coutant C, Huguet F, Gabos Z, Hsu L, Marpeau O, Uzan S, Pusztai L, Strom EA et al (2010) Nomogram to predict subsequent brain metastasis in patients with metastatic breast cancer. J Clin Oncol 28(12):2032–2037
Martin AM, Cagney DN, Catalano PJ, Warren LE, Bellon JR, Punglia RS, Claus EB, Lee EQ, Wen PY, Haas-Kogan DA, Alexander BM, Lin NU, Aizer AA (2017) Brain metastases in newly diagnosed breast cancer: A population-based study. JAMA Oncol 3(8):1069–1077
Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thurlimann B, HJ Senn, Panel M (2015) Tailoring therapies–improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncology 26(8):1533–1546
Cardoso F, Costa A, Senkus E, Aapro M, Andre F, Barrios CH, Bergh J, Bhattacharyya G, Biganzoli L, Cardoso MJ et al (2017) 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3). Ann Oncol 28:16–33
Priedigkeit N, Hartmaier RJ, Chen Y, Vareslija D, Basudan A, Watters RJ, Thomas R, Leone JP, Lucas PC, Bhargava R et al (2017) Intrinsic subtype switching and acquired ERBB2/HER2 amplifications and mutations in breast cancer brain metastases. JAMA Oncol 3(5):666–671
Thomson AH, McGrane J, Mathew J, Palmer J, Hilton DA, Purvis G, Jenkins R (2016) Changing molecular profile of brain metastases compared with matched breast primary cancers and impact on clinical outcomes. Br J Cancer 114(7):793–800
Duchnowska R, Dziadziuszko R, Trojanowski T, Mandat T, Och W, Czartoryska-Arlukowicz B, Radecka B, Olszewski W, Szubstarski F, Kozlowski W et al (2012) Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain. Breast Cancer Res 14(4):R119
Aurilio G, Disalvatore D, Pruneri G, Bagnardi V, Viale G, Curigliano G, Adamoli L, Munzone E, Sciandivasci A, De Vita F et al (2014) A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. Eur J Cancer 50(2):277–289
Duchnowska R, Sperinde J, Chenna A, Huang W, Weidler JM, Winslow J, Haddad M, Paquet A, Lie Y, Trojanowski T et al (2015) Quantitative HER2 and p95HER2 levels in primary breast cancers and matched brain metastases. Neuro Oncol 17(9):1241–1249
Bachmann C, Grischke EM, Fehm T, Staebler A, Schittenhelm J, Wallwiener D (2013) CNS metastases of breast cancer show discordant immunohistochemical phenotype compared to primary. J Cancer Res Clin Oncol 139(4):551–556
Gabos Z, Sinha R, Hanson J, Chauhan N, Hugh J, Mackey JR, Abdulkarim B (2006) Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J Clin Oncol 24(36):5658–5663
Heitz F, Harter P, Lueck HJ, Fissler-Eckhoff A, Lorenz-Salehi F, Scheil-Bertram S, Traut A, du Bois A (2009) Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases. Eur J Cancer 45(16):2792–2798
Tham YL, Sexton K, Kramer R, Hilsenbeck S, Elledge R (2006) Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 107(4):696–704
Gaedcke J, Traub F, Milde S, Wilkens L, Stan A, Ostertag H, Christgen M, von Wasielewski R, Kreipe HH (2007) Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer. Mod Pathol 20(8):864–870
Griggs JJ, Hamilton AS, Schwartz KL, Zhao W, Abrahamse PH, Thomas DG, Jorns JM, Jewell R, Saber ME, Haque R et al (2016) Discordance between original and central laboratories in ER and HER2 results in a diverse, population-based sample. Breast Cancer Res Treat 161:375–384
Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J et al (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
Cortes J, Rugo HS, Awada A, Twelves C, Perez EA, Im SA, Gomez-Pardo P, Schwartzberg LS, Dieras V, Yardley DA et al (2017) Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat 1–3
Zagar TM, Van Swearingen AE, Kaidar-Person O, Ewend MG, Anders CK (2016) Multidisciplinary management of breast cancer brain metastases. Oncology 30(10)
Van Swearingen AED, Sambade MJ, Siegel MB, Sud S, McNeill RS, Bevill SM, Chen X, Bash RE, Mounsey L, Golitz BT, Santos C, Deal A, Parker JS, Rashid N, Miller CR, Johnson GL, Anders CK (2017) Combined kinase inhibitors of MEK1/2 and either PI3K or PDGFR are efficacious in intracranial triple-negative breast cancer. Neuro Oncol. doi:10.1093/neuonc/nox052
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Kaidar-Person, O., Meattini, I., Jain, P. et al. Discrepancies between biomarkers of primary breast cancer and subsequent brain metastases: an international multicenter study. Breast Cancer Res Treat 167, 479–483 (2018). https://doi.org/10.1007/s10549-017-4526-8
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DOI: https://doi.org/10.1007/s10549-017-4526-8