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Breast Cancer Research
Published in: Breast Cancer Research 4/2012

Open Access 01-08-2012 | Research article

Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain

Authors: Renata Duchnowska, Rafał Dziadziuszko, Tomasz Trojanowski, Tomasz Mandat, Waldemar Och, Bogumiła Czartoryska-Arłukowicz, Barbara Radecka, Wojciech Olszewski, Franciszek Szubstarski, Wojciech Kozłowski, Bożena Jarosz, Wojciech Rogowski, Anna Kowalczyk, Janusz Limon, Wojciech Biernat, Jacek Jassem, the Polish Brain Metastasis Consortium

Published in: Breast Cancer Research | Issue 4/2012

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Abstract

Introduction

We investigated the status of estrogen receptor alpha (ERα), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival.

Methods

The study group included 120 breast cancer patients. ERα, PR, and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization.

Results

Using the Allred score of ≥ 3 as a threshold, conversion of ERα and PR in brain metastases occurred in 29% of cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ERα (P = 0.021) and PR (P = 0.001), mainly towards their loss. Receptor conversion had no significant impact on survival.

Conclusions

Receptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly affect survival.
Appendix
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Literature
1.
Lin NU, Bellon JR, Winer EP: CNS metastases in breast cancer. J Clin Oncol. 2004, 22: 3608-3617. 10.1200/JCO.2004.01.175.CrossRefPubMed
2.
Pestalozzi BC, Zahrieh D, Price KN, Holmberg SB, Lindtner J, Collins J, Crivellari D, Fey MF, Murray E, Pagani O, Simoncini E, Castiglione-Gertsch M, Gelber RD, Coates AS, Goldhirsch A: International Breast Cancer Study Group (IBCSG): identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol. 2006, 17: 935-944. 10.1093/annonc/mdl064.CrossRefPubMed
3.
Harrell JC, Prat A, Parker JS, Fan C, He X, Carey L, Anders C, Ewend M, Perou CM: Genomic analysis identifies unique signatures predictive of brain, lung, and liver relapse. Breast Cancer Res Treat. 2012, 132: 523-535. 10.1007/s10549-011-1619-7.CrossRefPubMed
4.
Gaedcke J, Traub F, Milde S, Wilkens L, Stan A, Ostertag H, Christgen M, von Wasielewski R, Kreipe HH: Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer. Modern Pathol. 2007, 20: 864-870. 10.1038/modpathol.3800830.CrossRef
5.
Crivellari D, Pagani O, Veronesi A, Lombardi D, Nolè F, Thürlimann B, Hess D, Borner M, Bauer J, Martinelli G, Graffeo R, Sessa C, Goldhirsch A, International Breast Cancer Study Group: High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel. Ann Oncol. 2001, 12: 353-356. 10.1023/A:1011132609055.CrossRefPubMed
6.
Ryberg M, Nielsen D, Osterlind K, Andersen PK, Skovsgaard T, Dombernowsky P: Predictors of central nervous system metastasis in patients with metastatic breast cancer: a competing risk analysis of 579 patients treated with epirubicin-based chemotherapy. Breast Cancer Res Treat. 2005, 91: 217-225. 10.1007/s10549-005-0323-x.CrossRefPubMed
7.
Duchnowska R, Szczylik C: Central nervous system metastases in breast cancer patients administered trastuzumab. Cancer Treat Rev. 2005, 31: 312-318. 10.1016/j.ctrv.2005.04.008.CrossRefPubMed
8.
Guarneri V, Giovannelli S, Ficarra G, Bettelli S, Maiorana A, Piacentini F, Barbieri E, Dieci MV, D'Amico R, Jovic G, Conte P: Comparison of HER-2 and hormone receptor expression in primary breast cancers and asynchronous paired metastases: impact on patient management. Oncologist. 2008, 13: 838-844. 10.1634/theoncologist.2008-0048.CrossRefPubMed
9.
Hoefnagel LD, van de Vijver MJ, van Slooten HJ, Wesseling P, Wesseling J, Westenend PJ, Bart J, Seldenrijk CA, Nagtegaal ID, Oudejans J, van der Valk P, van der Groep P, de Vries EG, van der Wall E, van Diest PJ: Receptor conversion in distant breast cancer metastases. Breast Cancer Res. 2010, 12: R75-10.1186/bcr2645.CrossRefPubMedPubMedCentral
10.
Curigliano G, Bagnardi V, Viale G, Fumagalli L, Rotmensz N, Aurilio G, Locatelli M, Pruneri G, Giudici S, Bellomi M, Della Vigna P, Monfardini L, Orsi F, Nolè F, Munzone E, Goldhirsch A: Should liver metastases of breast cancer be biopsied to improve treatment choice?. Ann Oncol. 2011, 22: 2227-2233. 10.1093/annonc/mdq751.CrossRefPubMed
11.
Gong Y, Han EY, Guo M, Pusztai L, Sneige L: Stability of estrogen receptor status in breast carcinoma: a comparison between primary and metastatic tumors with regard to disease course and intervening systemic therapy. Cancer. 2011, 117: 705-713. 10.1002/cncr.25506.CrossRefPubMed
12.
Liedtke C, Broglio K, Moulder S, Hsu L, Kau SW, Symmans WF, Albarracin C, Meric-Bernstam F, Woodward W, Theriault RL, Kiesel L, Hortobagyi GN, Pusztai L, Gonzalez-Angulo AM: Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Ann Oncol. 2009, 20: 1953-1958. 10.1093/annonc/mdp263.CrossRefPubMedPubMedCentral
13.
Karlsson E, Lindstrom LS, Wilking U, Skoog L, Johansson U, Bergh : Discordance in hormone receptor status in breast cancer during tumor progression. J Clin Oncol. 2010, 28 (suppl): s116-
14.
Houssami N, Macaskill P, Balleine RL, Bilous M, Pegram MD: HER2 discordance between primary breast cancer and its paired metastasis: tumor biology or test artefact? insights through meta-analysis. Breast Cancer Res Treat. 2011, 129: 659-674. 10.1007/s10549-011-1632-x.CrossRefPubMed
15.
Xiao C, Gong Y, Han EY, Gonzalez-Angulo AM, Sneige N: Stability of HER2-positive status in breast carcinoma: a comparison between primary and paired metastatic tumors with regard to the possible impact of intervening trastuzumab treatment. Ann Oncol. 2011, 22: 1547-1553. 10.1093/annonc/mdq623.CrossRefPubMed
16.
Chang HJ, Han SW, Oh DY, Im SA, Jeon YK, Park IA, Han W, Noh DY, Bang YJ, Kim TY: Discordant human epidermal growth factor receptor 2 and hormone receptor status in primary and metastatic breast cancer and response to trastuzumab. Jpn J Clin Oncol. 2011, 41: 593-599. 10.1093/jjco/hyr020.CrossRefPubMed
17.
Grupka NL, Lear-Kaul KC, Kleinschmidt-DeMasters BK, Singh M: Epidermal growth factor receptor status in breast cancer metastases to the central nervous system: comparison with HER-2/neu status. Arch Pathol Lab Med. 2004, 128: 974-979.PubMed
18.
Yonemori K, Tsuta KC, Shimizu C, Hatanaka Y, Hashizume K, Ono M, Nakanishi Y, Hasegawa T, Miyakita Y, Narita Y, Shibui S, Fujiwara Y: Immunohistochemical profiles of brain metastases from breast cancer. J Neurooncol. 2008, 90: 223-228. 10.1007/s11060-008-9654-x.CrossRefPubMed
19.
Shao M, Liu J, Vong JS, Shao MM, Niu Y, Germin B, Tang P, Chan AW, Lui PC, Law BK, Tan PH, Tse GM: A subset of breast cancer predisposes to brain metastasis. Med Mol Morphol. 2011, 44: 15-20. 10.1007/s00795-010-0495-2.CrossRefPubMed
20.
Fuchs IB, Loebbecke M, Buhler H, Stoltenburg-Didinger G, Heine B, Lichtenegger W, Schaller G: HER2 in brain metastases: issues of concordance, survival, and treatment. J Clin Oncol. 2002, 20: 4130-4133. 10.1200/JCO.2002.99.148.CrossRefPubMed
21.
Brogi E, Murphy CG, Johnson ML, Conlin AK, Hsu M, Patil S, Akram M, Nehhozina T, Jhaveri KL, Hudis CA, Seidman AD: Breast carcinoma with brain metastases: clinical analysis and immunoprofile on tissue microarrays. Ann Oncol. 2011, 22: 2597-2603. 10.1093/annonc/mdr022.CrossRefPubMed
22.
Lear-Kaul KC, Yoon HR, Kleinschmidt-DeMasters BK, McGavran L, Singh M: Her-2/neu status in breast cancer metastases to the central nervous system. Arch Pathol Lab Med. 2003, 127: 1451-1457.PubMed
23.
Allred DC, Harvey JM, Berardo M, Clark GM: Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998, 11: 155-168.PubMed
24.
Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010, 28: 2784-2795. 10.1200/JCO.2009.25.6529.CrossRefPubMedPubMedCentral
25.
Landis JR, Koch GG: The measurement of observer agreement for categorical data. Biometrics. 1977, 33: 159-174. 10.2307/2529310.CrossRefPubMed
26.
Amir E, Miller N, Geddie W, Freedman O, Kassam F, Simmons C, Oldfield M, Dranitsaris G, Tomlinson G, Laupacis A, Tannock IF, Clemons M: Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol. 2012, 30: 587-592. 10.1200/JCO.2010.33.5232.CrossRefPubMed
27.
Amir E, Clemons M, Purdie CA, Miller N, Quinlan P, Geddie W, Coleman RE, Freedman OC, Jordan LB, Thompson AM: Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of multi-centre, multi-disciplinary prospective studies. Cancer Treat Rev. 2012, 38: 708-714. 10.1016/j.ctrv.2011.11.006.CrossRefPubMed
28.
Ding L, Ellis Matthew J, Li S, Larson DE, Chen K, Wallis JW, Harris CC, McLellan MD, Fulton RS, Fulton LL, Abbott RM, Hoog J, Dooling DJ, Koboldt DC, Schmidt H, Kalicki J, Zhang Q, Chen L, Lin L, Wendl MC, McMichael JF, Magrini VJ, Cook L, McGrath SD, Vickery TL, Appelbaum E, Deschryver K, Davies S, Guintoli T, et al: Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature. 2010, 464: 999-1005. 10.1038/nature08989.CrossRefPubMedPubMedCentral
29.
Simmons C, Miller N, Geddie W, Gianfelice D, Oldfield M, Dranitsaris G, Clemons MJ: Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases?. Ann Oncol. 2009, 20: 1499-1504. 10.1093/annonc/mdp028.CrossRefPubMedPubMedCentral
30.
Kuukajarvi T, Karhu R, Tanner M, Kähkönen M, Schäffer A, Nupponen N, Pennanen S, Kallioniemi A, Kallioniemi OP, Isola J: Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer. Cancer Res. 1997, 57: 1597-1604.
31.
Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak K: Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007, 11: 259-273. 10.1016/j.ccr.2007.01.013.CrossRefPubMed
32.
Hoefnagel LD, Moelans CB, Meijer SL, van Slooten HJ, Wesseling P, Wesseling J, Westenend PJ, Bart J, Seldenrijk CA, Nagtegaal ID, Oudejans J, van der Valk P, van Gils CH, van der Wall E, van Diest PJ: Prognostic value of estrogen receptor α and progesterone receptor conversion in distant breast cancer metastases. Cancer. 2012, Mar 13. doi: 10.1002/cncr.27518,
33.
Niikura N, Liu J, Hayashi N, Mittendorf EA, Gong Y, Palla SL, Tokuda Y, Gonzalez-Angulo AM, Hortobagyi GN, Ueno NT: Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol. 2012, 30: 593-599. 10.1200/JCO.2010.33.8889.CrossRefPubMed
34.
Chen G, Davies MA: Emerging insights into the molecular biology of brain metastases. Biochem Pharmacol. 2012, 83: 305-314. 10.1016/j.bcp.2011.09.012.CrossRefPubMed
35.
36.
Smid M, Wang Y, Zhang Y, Sieuwerts AM, Yu J, Klijn JG, Foekens JA, Martens JW: Subtypes of breast cancer show preferential site of relapse. Cancer Res. 2008, 68: 3108-3114. 10.1158/0008-5472.CAN-07-5644.CrossRefPubMed
37.
Kennecke H, Yerushalmi R, Woods R, Cheang MC, Voduc D, Speers CH, Nielsen TO, Gelmon K: Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010, 28: 3271-3277. 10.1200/JCO.2009.25.9820.CrossRefPubMed
38.
Pusztai L, Viale G, Kelly CM, Hudis CA: Estrogen and HER-2 receptor discordance between primary breast cancer and metastasis. Oncologist. 2010, 15: 1164-1168. 10.1634/theoncologist.2010-0059.CrossRefPubMedPubMedCentral
39.
Weigelt B, Glass AM, Wessels LF, Witteveen AT, Peterse JL, van't Veer LJ: Gene expression profiles of primary breast tumors maintained in distant metastases. Proc Natl Acad Sci USA. 2003, 100: 15901-15905. 10.1073/pnas.2634067100.CrossRefPubMedPubMedCentral
40.
Duchnowska R, Jassem J, Shen C, Thorat M, Li L, Morimiya A, Zhao Q, Biernat W, Mandat T, Staszkiewicz R, Och W, Szostak W, Gugala K, Trojanowski T, Czartoryska-Arlukowicz B, Szczylik C, Nakshatri H, Steeg P, Sledge G, Badve S: Molecular characteristics of matched brain metastasis (BM) versus the primary breast cancer (PBC). Cancer Res. 2009, 69 (suppl 2): s164-
41.
Chung GG, Zerkowski MP, Ghosh S, Camp RL, Rimm DL: Quantitative analysis of estrogen receptor heterogeneity in breast cancer. Lab Invest. 2007, 87: 662-669. 10.1038/labinvest.3700543.CrossRefPubMed
42.
Cardoso F, Fallowfield L, Costa A, Castiglione M, Senkus E, ESMO Guidelines Working Group: Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011, 22 (suppl 6): vi25-vi30.PubMed
43.
Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, et al: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (abridged version). Arch Pathol Lab Med. 2010, 134: e48-72.PubMed
44.
Bachelot TD, Romieu G, Campone M, Dieras V, Cropet C, Roche HH, Jimenez M, Le Rhun E, Pierga J, Gonçalves A, Leheurteur M, Domont J, Gutierrez M, Cure H, Ferrero J, Labbe C: LANDSCAPE: a FNCLCC phase II study with lapatinib and capecitabine in patients with brain metastases from HER2-positive metastatic breast cancer before whole brain radiotherapy. J Clin Oncol. 2011, 29 (suppl): s47-
Metadata
Title
Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain
Authors
Renata Duchnowska
Rafał Dziadziuszko
Tomasz Trojanowski
Tomasz Mandat
Waldemar Och
Bogumiła Czartoryska-Arłukowicz
Barbara Radecka
Wojciech Olszewski
Franciszek Szubstarski
Wojciech Kozłowski
Bożena Jarosz
Wojciech Rogowski
Anna Kowalczyk
Janusz Limon
Wojciech Biernat
Jacek Jassem
the Polish Brain Metastasis Consortium
Publication date
01-08-2012
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2012
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3244

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