Top

Published in:

Open Access 01-04-2018 | Clinical Study

Discordances in ER, PR, and HER2 between primary breast cancer and brain metastasis

Authors: Jaehag Jung, Seung Hoon Lee, Mira Park, Ji Hye Youn, Sang Hoon Shin, Ho Shin Gwak, Heon Yoo

Published in: Journal of Neuro-Oncology | Issue 2/2018

Abstract

When distant metastases are discovered, it is important to determine receptor profiles of these lesions through histologic examination. However, brain metastasis sites are difficult to reach to be routinely biopsied. The purpose of this study was to determine expression profiles of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in breast cancer brain metastasis (BCBM) and the existence of discordance between primary breast cancer and brain metastasis. A total of 37 patients who underwent craniotomies for metastatic brain tumors arising from breast cancer at National Cancer Center (NCC) of Korea between 2002 and 2014 were retrospectively reviewed. Clinicopathologic data were collected from electronic medical records. Receptor profiles of primary breast cancer and brain metastasis in each patient were identified. Data of ER, PR, and HER2 expression in brain metastasis were available in electronic medical records for 21 (56.8%) of 37 cases. Results of ER, PR, and HER2 expression were positive in 47.6, 42.9, and 38.1% of patients with brain metastasis, respectively. Receptor conversion occurred in 11 (52.4%) of 21 patients (for ER, 9.5%; for PR, 38.1%; for HER2, 23.8%). Overall survival was longer in patients with concordant receptor expression patterns between primary breast cancer and brain lesion compared to that in patients with discordant patterns. However, such difference was not statistically significant (discordant vs. concordant median survival: 19.2 versus 31.1 months, p = 0.181). Receptor conversion in BCBMs was observed in over 50% of Korean patients used in this study. HER2 conversion was observed in 23.8% of patients in this study. Therefore, if resistance to anti-HER2 treatment is suspected in patients with BCBM, biopsy is needed to determine receptor profiles of brain lesion.

Oh CM, Won YJ, Jung KW, Kong HJ, Cho H, Lee JK, Lee DH, Lee KH (2016) Community of population-based regional cancer R: cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2013. Cancer Res Treat 48(2):436–450CrossRef

Lin NU, Bellon JR, Winer EP (2004) CNS metastases in breast cancer. J Clin Oncol 22(17):3608–3617CrossRef

Lee SS, Ahn JH, Kim MK, Sym SJ, Gong G, Ahn SD, Kim SB, Kim WK (2008) Brain metastases in breast cancer: prognostic factors and management. Breast Cancer Res Treat 111(3):523–530CrossRef

Brogi E, Murphy CG, Johnson ML, Conlin AK, Hsu M, Patil S, Akram M, Nehhozina T, Jhaveri KL, Hudis CA et al (2011) Breast carcinoma with brain metastases: clinical analysis and immunoprofile on tissue microarrays. Ann Oncol 22(12):2597–2603CrossRef

Nam BH, Kim SY, Han HS, Kwon Y, Lee KS, Kim TH, Ro J (2008) Breast cancer subtypes and survival in patients with brain metastases. Breast Cancer Res 10(1):R20CrossRef

Yap YS, Cornelio GH, Devi BC, Khorprasert C, Kim SB, Kim TY, Lee SC, Park YH, Sohn JH, Sutandyo N et al (2012) Brain metastases in Asian HER2-positive breast cancer patients: anti-HER2 treatments and their impact on survival. Br J Cancer 107(7):1075–1082CrossRef

Hoefnagel LD, van de Vijver MJ, van Slooten HJ, Wesseling P, Wesseling J, Westenend PJ, Bart J, Seldenrijk CA, Nagtegaal ID, Oudejans J et al (2010) Receptor conversion in distant breast cancer metastases. Breast Cancer Res 12(5):R75CrossRef

Lin NU (2010) Concordance of HER2 in primary tumor and leptomeningeal metastases: now what? Breast Cancer Res Treat 123(1):129–131CrossRef

Omoto Y, Kurosumi M, Hozumi Y, Oba H, Kawanowa K, Takei H, Yasuda Y (2010) Immunohistochemical assessment of primary breast tumors and metachronous brain metastases, with particular regard to differences in the expression of biological markers and prognosis. Exp Ther Med 1(4):561–567CrossRef

10.

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):R119CrossRef

11.

Niikura N, Liu J, Hayashi N, Mittendorf EA, Gong Y, Palla SL, Tokuda Y, Gonzalez-Angulo AM, Hortobagyi GN, Ueno NT (2012) Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol 30(6):593–599CrossRef

12.

Kroigard AB, Larsen MJ, Thomassen M, Kruse TA (2016) Molecular concordance between primary breast cancer and matched metastases. Breast J 22(4):420–430CrossRef

13.

Yeung C, Hilton J, Clemons M, Mazzarello S, Hutton B, Haggar F, Addison CL, Kuchuk I, Zhu X, Gelmon K et al (2016) Estrogen, progesterone, and HER2/neu receptor discordance between primary and metastatic breast tumours-a review. Cancer Metastasis Rev 35(3):427–437CrossRef

14.

Lindstrom LS, Karlsson E, Wilking UM, Johansson U, Hartman J, Lidbrink EK, Hatschek T, Skoog L, Bergh J (2012) Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol 30(21):2601–2608CrossRef

15.

Amir E, Miller N, Geddie W, Freedman O, Kassam F, Simmons C, Oldfield M, Dranitsaris G, Tomlinson G, Laupacis A et al (2012) Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol 30(6):587–592CrossRef

16.

Park IH, Ro J, Lee KS, Nam BH, Kwon Y, Shin KH (2009) Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer. Ann Oncol 20(1):56–62CrossRef

17.

Dijkers EC, Oude Munnink TH, Kosterink JG, Brouwers AH, Jager PL, de Jong JR, van Dongen GA, Schroder CP, Lub-de Hooge MN, de Vries EG (2010) Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther 87(5):586–592CrossRef

18.

Swain SM, Baselga J, Miles D, Im YH, Quah C, Lee LF, Cortes J (2014) Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA. Ann Oncol 25(6):1116–1121CrossRef

19.

Krop IE, Lin NU, Blackwell K, Guardino E, Huober J, Lu M, Miles D, Samant M, Welslau M, Dieras V (2015) Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol 26(1):113–119CrossRef

20.

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):864–870CrossRef

21.

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 Neuro-Oncol 90(2):223–228CrossRef

22.

Shao MM, Liu J, Vong JS, Niu Y, Germin B, Tang P, Chan AW, Lui PC, Law BK, Tan PH et al (2011) A subset of breast cancer predisposes to brain metastasis. Med Mol Morphol 44(1):15–20CrossRef

23.

Allott EH, Geradts J, Sun X, Cohen SM, Zirpoli GR, Khoury T, Bshara W, Chen M, Sherman ME, Palmer JR et al (2016) Intratumoral heterogeneity as a source of discordance in breast cancer biomarker classification. Breast Cancer Res 18(1):68CrossRef

24.

Nardone A, De Angelis C, Trivedi MV, Osborne CK, Schiff R (2015) The changing role of ER in endocrine resistance. Breast 24(Suppl 2):S60–S66CrossRef

25.

Pohlmann PR, Mayer IA, Mernaugh R (2009) Resistance to trastuzumab in breast cancer. Clin Cancer Res 15(24):7479–7491CrossRef

Title: Discordances in ER, PR, and HER2 between primary breast cancer and brain metastasis
Authors: Jaehag Jung
Seung Hoon Lee
Mira Park
Ji Hye Youn
Sang Hoon Shin
Ho Shin Gwak
Heon Yoo
Publication date: 01-04-2018
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2018
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-017-2717-0

At a glance: The STEP trials

Springer Medicine

Discordances in ER, PR, and HER2 between primary breast cancer and brain metastasis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2018

Analysis of immunobiologic markers in primary and recurrent glioblastoma

Treatment and outcomes of 28 patients with spinal metastasis from gynecological cancer

Immunophenotyping of pediatric brain tumors: correlating immune infiltrate with histology, mutational load, and survival and assessing clonal T cell response

Localized targeted antiangiogenic drug delivery for glioblastoma

A combined diffusion tensor imaging and Ki-67 labeling index study for evaluating the extent of tumor infiltration using the F98 rat glioma model

Overexpression of aryl hydrocarbon receptor (AHR) signalling pathway in human meningioma