nach oben

Erschienen in:

01.06.2014 | Preclinical study

Prognostic and biological significance of proliferation and HER2 expression in the luminal class of breast cancer

verfasst von: Dena A. Jerjees, M. Alabdullah, Andrew R. Green, Alaa Alshareeda, R. D. Macmillan, Ian O. Ellis, Emad A. Rakha

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

The definition of Luminal-B subclass of breast cancer (BC) varies in literature. In this study, we have compared the proliferation status; assessed using KI67 labeling index (KI67-LI), and HER2-expression in estrogen receptor positive (ER+) BC to assess their impact on the biological and clinical characteristics of luminal-BC. 1547 (73.8 %) well-characterized clinically annotated stage I–III ER + BC were assessed for expression of KI67, HER2 (ASCO guidelines), and a large panel of relevant biomarkers (no = 37). 46.3 % of the cases show high KI67-LI (>13 %) and 8.4 % show HER2+ and both markers are positively associated with younger age, higher tumor grade and poorer outcome. High KI67-LI and HER2+ are associated with upregulation of ER-coactivators and proliferation-related markers and with downregulation of good prognostic markers. High KI67-LI is associated with larger size, advanced stage, and lymphovascular invasion (LVI) and with downregulation of luminal-enriched and DNA-damage repair markers. In contrast, HER2+ is associated with upregulation of ER-regulated proteins and E-cadherin. When analysis is restricted to high KI67-LI subgroup, HER2+ shows an association with upregulation of differentiation-associated proteins and E-cadherin. Conversely, within HER2+ class, high KI67-LI maintains its association with downregulation of differentiation-associated/luminal-enriched proteins. Outcome analyses indicate that both markers are independently associated with shorter survival but HER2+ is associated with a worse outcome. Although both are associated with high proliferation and poor prognosis within ER + BC, HER2+ is less frequent than high KI67-LI. Unlike KI67, HER2 seems to independently drive the aggressive behavior of ER+ tumors without downregulation of luminal proteins.

Anderson E (2002) The role of oestrogen and progesterone receptors in human mammary development and tumorigenesis. Breast Cancer Res 4(5):197–201PubMedCentralPubMedCrossRef

Clarke RB, Anderson E, Howell A (2004) Steroid receptors in human breast cancer. Trends Endocrinol Metab 15(7):316–323PubMedCrossRef

Mosselman S, Polman J, Dijkema R (1996) ERβ: identification and characterization of a novel human estrogen receptor. FEBS Lett 392(1):49–53PubMedCrossRef

Ctsu RI (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717CrossRef

Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA et al (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752PubMedCrossRef

Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98(19):10869–10874PubMedCentralPubMedCrossRef

Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 100(14):8418–8423PubMedCentralPubMedCrossRef

Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z et al (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27(8):1160–1167PubMedCentralPubMedCrossRef

Badve S, Turbin D, Thorat MA, Morimiya A, Nielsen TO, Perou CM, Dunn S, Huntsman DG, Nakshatri H (2007) FOXA1 expression in breast cancer–correlation with luminal subtype A and survival. Clin Cancer Res 13(15):4415–4421PubMedCrossRef

10.

Matos I, Dufloth R, Alvarenga M, Zeferino LC, Schmitt F (2005) p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas. Virchows Arch 447(4):688–694PubMedCrossRef

11.

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S et al (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295(21):2492–2502PubMedCrossRef

12.

Guiu S, Michiels S, Andre F, Cortes J, Denkert C, Di Leo A, Hennessy BT, Sorlie T, Sotiriou C, Turner N et al (2012) Molecular subclasses of breast cancer: how do we define them? The IMPAKT 2012 Working Group Statement. Ann Oncol 23(12):2997–3006PubMedCrossRef

13.

Hugh J, Hanson J, Cheang MCU, Nielsen TO, Perou CM, Dumontet C, Reed J, Krajewska M, Treilleux I, Rupin M et al (2009) Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol 27(8):1168–1176PubMedCentralPubMedCrossRef

14.

Bhargava R, Dabbs D (2008) Luminal B breast tumors are not HER2 positive. Breast Cancer Res 10(5):404PubMedCentralPubMedCrossRef

15.

Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, Watson M, Davies S, Bernard PS, Parker JS et al (2009) Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 101(10):736–750PubMedCentralPubMedCrossRef

16.

Osborne CK, Bardou V, Hopp TA, Chamness GC, Hilsenbeck SG, Fuqua SAW, Wong J, Allred DC, Clark GM, Schiff R (2003) Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. J Natl Cancer Inst 95(5):353–361PubMedCrossRef

17.

Viale G, Regan MM, Mastropasqua MG, Maffini F, Maiorano E, Colleoni M, Price KN, Golouh R, Perin T, Brown R (2008) Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst 100(3):207–212PubMedCrossRef

18.

Urruticoechea A, Smith IE, Dowsett M (2005) Proliferation marker Ki-67 in early breast cancer. J Clin Oncol 23(28):7212–7220PubMedCrossRef

19.

Liu S, Edgerton SM, Moore DH, Thor AD (2001) Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. Clin Cancer Res 7(6):1716–1723PubMed

20.

Spyratos F, Ferrero-Poüs M, Trassard M, Hacene K, Phillips E, Tubiana-Hulin M, Le Doussal V (2002) Correlation between MIB-1 and other proliferation markers. Cancer 94(8):2151–2159PubMedCrossRef

21.

Brown RW, Allred C, Clark GM, Osborne CK, Hilsenbeck SG (1996) Prognostic value of Ki-67 compared to S-phase fraction in axillary node-negative breast cancer. Clin Cancer Res 2(3):585–592PubMed

22.

Galea MH, Blamey RW, Elston CE, Ellis IO (1992) The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22(3):207–219PubMedCrossRef

23.

Rakha EA, El-Sayed ME, Powe DG, Green AR, Habashy H, Grainge MJ, Robertson JFR, Blamey R, Gee J, Nicholson RI et al (2008) Invasive lobular carcinoma of the breast: response to hormonal therapy and outcomes. Eur J Cancer 44(1):73–83PubMedCrossRef

24.

Cheang MCU, Chia SK, Voduc D, Gao D, Leung S, Snider J, Watson M, Davies S, Bernard PS, Parker JS (2009) Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 101(10):736–750PubMedCentralPubMedCrossRef

25.

Rakha EA, Elsheikh SE, Aleskandarany MA, Habashi HO, Green AR, Powe DG, El-Sayed ME, Benhasouna A, Brunet JS, Akslen LA et al (2009) Triple-negative breast cancer: distinguishing between basal and nonbasal subtypes. Clin Cancer Res 15(7):2302–2310PubMedCrossRef

26.

Rakha EA, El-Sheikh SE, Kandil MA, El-Sayed ME, Green AR, Ellis IO (2008) Expression of BRCA1 protein in breast cancer and its prognostic significance. Hum Pathol 39(6):857–865PubMedCrossRef

27.

Habashy HO, Rakha EA, Ellis IO, Powe DG (2013) The oestrogen receptor coactivator CARM1 has an oncogenic effect and is associated with poor prognosis in breast cancer. Breast Cancer Res Treat 140(2):307–316PubMedCrossRef

28.

Alshareeda AT, Negm OH, Albarakati N, Green AR, Nolan C, Sultana R, Madhusudan S, Benhasouna A, Tighe P, Ellis IO et al (2013) Clinicopathological significance of KU70/KU80, a key DNA damage repair protein in breast cancer. Breast Cancer Res Treat 139(2):301–310PubMedCrossRef

29.

García-Caballero T, Grabau D, Green AR, Gregory J, Schad A, Kohlwes E, Ellis IO, Watts S, Mollerup J (2010) Determination of HER2 amplification in primary breast cancer using dual-colour chromogenic in situ hybridization is comparable to fluorescence in situ hybridization: a European multicentre study involving 168 specimens. Histopathology 56(4):472–480PubMedCentralPubMedCrossRef

30.

Abd El-Rehim DM, Ball G, Pinder SE, Rakha E, Paish C, Robertson JFR, Macmillan D, Blamey RW, Ellis IO (2005) 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 116(3):340–350PubMedCrossRef

31.

Rakha EA, El-Sayed ME, Green AR, Lee AHS, Robertson JF, Ellis IO (2006) Prognostic markers in triple-negative breast cancer. Cancer 109(1):25–32CrossRef

32.

Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, Van De Rijn M, Jeffrey SS (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci 98(19):10869PubMedCentralPubMedCrossRef

33.

Sørlie T, Tibshirani R, Parker J, Hastie T, Marron J, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci 100(14):8418PubMedCentralPubMedCrossRef

34.

Draghici S, Khatri P, Eklund AC, Szallasi Z (2006) Reliability and reproducibility issues in DNA microarray measurements. Trends Genet 22(2):101–109PubMedCentralPubMedCrossRef

35.

Oh DS, Troester MA, Usary J, Hu Z, He X, Fan C, Wu J, Carey LA, Perou CM (2006) Estrogen-regulated genes predict survival in hormone receptor-positive breast cancers. J Clin Oncol 24(11):1656–1664PubMedCrossRef

36.

Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, Nordgren H, Farmer P, Praz V, Haibe-Kains B et al (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98(4):262–272PubMedCrossRef

37.

Cheang MCU, Chia SK, Voduc D, Gao D, Leung S, Snider J, Watson M, Davies S, Bernard PS, Parker JS et al (2009) Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 101(10):736–750PubMedCentralPubMedCrossRef

38.

Aleskandarany MA, Green AR, Benhasouna AA, Barros FF, Neal K, Reis-Filho JS, Ellis IO, Rakha EA (2012) Prognostic value of proliferation assay in the luminal, HER2-positive, and triple-negative biologic classes of breast cancer. Breast Cancer Res 14(1):R3PubMedCentralPubMedCrossRef

39.

Ihemelandu CU, Leffall LSD, Dewitty RL, Naab TJ, Mezghebe HM, Makambi KH, Adams-Campbell L, Frederick WA (2007) Molecular breast cancer subtypes in premenopausal African-American women, tumor biologic factors and clinical outcome. Ann Surg Oncol 14(10):2994–3003PubMedCrossRef

40.

Kurebayashi J, Moriya T, Ishida T, Hirakawa H, Kurosumi M, Akiyama F, Kinoshita T, Takei H, Takahashi K, Ikeda M (2007) The prevalence of intrinsic subtypes and prognosis in breast cancer patients of different races. Breast 16:72–77CrossRef

41.

Onitilo AA, Engel JM, Greenlee RT, Mukesh BN (2009) Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res 7(1–2):4PubMedCentralPubMedCrossRef

42.

Hu Z, Fan C, Oh D, Marron J, He X, Qaqish B, Livasy C, Carey L, Reynolds E, Dressler L (2006) The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genom 7(1):96CrossRef

43.

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P et al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: american society of clinical oncology/college of american pathologists clinical practice guideline update. J Clin Oncol 31(31):3997–4013PubMedCrossRef

44.

Staaf J, Ringnér M, Vallon-Christersson J, Jönsson G, Bendahl PO, Holm K, Arason A, Gunnarsson H, Hegardt C, Agnarsson BA (2010) Identification of subtypes in human epidermal growth factor receptor 2–positive breast cancer reveals a gene signature prognostic of outcome. J Clin Oncol 28(11):1813–1820PubMedCrossRef

Titel: Prognostic and biological significance of proliferation and HER2 expression in the luminal class of breast cancer
verfasst von: Dena A. Jerjees
M. Alabdullah
Andrew R. Green
Alaa Alshareeda
R. D. Macmillan
Ian O. Ellis
Emad A. Rakha
Publikationsdatum: 01.06.2014
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2014
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-014-2941-7

Springer Medizin

Prognostic and biological significance of proliferation and HER2 expression in the luminal class of breast cancer

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2014

Use of menopausal hormone therapy and risk of ductal and lobular breast cancer among women 55–74 years of age

Letter in response: breast cancer screening of women aged 70–74 years

Double heterozygotes among breast cancer patients analyzed for BRCA1, CHEK2, ATM, NBN/NBS1, and BLM germ-line mutations

Clinical and molecular characterization of the BRCA2 p.Asn3124Ile variant reveals substantial evidence for pathogenic significance

Randomized phase II study of weekly paclitaxel with and without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA breast cancer without HER2 overexpression

The endoplasmic reticulum stress markers GRP78 and CHOP predict disease-free survival and responsiveness to chemotherapy in breast cancer

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie