Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2010

01-04-2010 | Clinical trial

Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up

Authors: Lisa Rydén, Karin Jirström, Monica Haglund, Olle Stål, Mårten Fernö

Published in: Breast Cancer Research and Treatment | Issue 2/2010

Login to get access

Abstract

Triple-negative breast cancer (TNB) has poor prognosis and moreover patients with TNB do not benefit from established targeted drugs with endocrine therapy or trastuzumab. The aim of the study was to analyze the prevalence of candidate biomarkers in tumors from patients with TNB. Tissue microarrays were prepared from primary tumors from premenopausal breast cancer patients (500/564) randomized to adjuvant tamoxifen or no adjuvant treatment. Immunohistochemical (IHC) staining included ER, PR, HER2, epidermal receptor growth factor (EGFR), vascular endothelial growth factor A (VEGF-A), and vascular endothelial growth factor receptor 2 (VEGFR2). EGFR and HER2 gene copy number was defined by fluorescence in situ hybridization (FISH). All patients were included in the descriptive analysis, but only untreated patients in the survival analysis. TNB was diagnosed in 96 patients and correlated significantly to low age, Nottingham histological grade (NHG) III, high Ki67-index, T2 tumors, node negativity, EGFR positivity, increased EGFR gene copy number and high VEGFR2 expression. TNB was an independent prognostic factor for decreased 5-year breast cancer specific survival (BCSS) (HR 2.0 (95% CI 1.1–3.6), P = 0.01), but not for 10-year BCSS. High VEGFR2 expression was significantly correlated to decreased BCSS in TNB patients. TNB was associated with decreased BCSS and clinicopathological characteristics of an aggressive tumor type. High VEGFR2 expression, EGFR expression, and EGFR gene copy number were significantly correlated to TNB, supporting their role as putative candidate biomarkers for selection of targeted therapy in TNB.
Literature
1.
go back to reference Sorlie T, Perou C, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874CrossRefPubMed Sorlie T, Perou C, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874CrossRefPubMed
2.
go back to reference Nielsen TO, Hsu FD, Jensen K et al (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10(16):5367–5374CrossRefPubMed Nielsen TO, Hsu FD, Jensen K et al (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10(16):5367–5374CrossRefPubMed
3.
go back to reference Livasy CA, Karaca G, Nanda R et al (2006) Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 19(2):264–271CrossRefPubMed Livasy CA, Karaca G, Nanda R et al (2006) Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 19(2):264–271CrossRefPubMed
4.
go back to reference Lerma E, Peiro G, Ramón T et al (2007) Immunohistochemical heterogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and Her2//neu (basal-like breast carcinomas). Mod Pathol 20(11):1200–1207CrossRefPubMed Lerma E, Peiro G, Ramón T et al (2007) Immunohistochemical heterogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and Her2//neu (basal-like breast carcinomas). Mod Pathol 20(11):1200–1207CrossRefPubMed
5.
go back to reference Rakha EA, El-Sayed ME, Green AR et al (2007) Prognostic markers in triple-negative breast cancer. Cancer 109(1):25–32CrossRefPubMed Rakha EA, El-Sayed ME, Green AR et al (2007) Prognostic markers in triple-negative breast cancer. Cancer 109(1):25–32CrossRefPubMed
6.
go back to reference Bauer KR, Brown M, Cress RD et al (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 109(9):1721–1728CrossRefPubMed Bauer KR, Brown M, Cress RD et al (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 109(9):1721–1728CrossRefPubMed
7.
go back to reference Rhee J, Han SW, Oh DY et al (2008) The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer. BMC Cancer 8(1):307CrossRefPubMed Rhee J, Han SW, Oh DY et al (2008) The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer. BMC Cancer 8(1):307CrossRefPubMed
8.
go back to reference Carey LA, Dees EC, Sawyer L et al (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8):2329–2334CrossRefPubMed Carey LA, Dees EC, Sawyer L et al (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8):2329–2334CrossRefPubMed
9.
go back to reference Cleator S, Heller W, Coombes RC (2007) Triple-negative breast cancer: therapeutic options. Lancet Oncol 8(3):235–244CrossRefPubMed Cleator S, Heller W, Coombes RC (2007) Triple-negative breast cancer: therapeutic options. Lancet Oncol 8(3):235–244CrossRefPubMed
10.
go back to reference Pal S, Mortimer J (2009) Triple-negative breast cancer: novel therapies and new directions. Maturitas 63(4):269–274CrossRefPubMed Pal S, Mortimer J (2009) Triple-negative breast cancer: novel therapies and new directions. Maturitas 63(4):269–274CrossRefPubMed
11.
go back to reference Carey LA, Perou C, Livasy CA et al (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295(21):2492–2502CrossRefPubMed Carey LA, Perou C, Livasy CA et al (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295(21):2492–2502CrossRefPubMed
12.
go back to reference Dent R, Trudeau M, Pritchard KI et al (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13(15 Pt 1):4429–4434CrossRefPubMed Dent R, Trudeau M, Pritchard KI et al (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13(15 Pt 1):4429–4434CrossRefPubMed
13.
go back to reference Miller K, Wang M, Gralow J et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676CrossRefPubMed Miller K, Wang M, Gralow J et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676CrossRefPubMed
14.
go back to reference Ryan PD, Tung NM, Isakoff SJ et al (2009) Neoadjuvant cisplatin and bevacizumab in triple negative breast cancer (TNBC): safety and efficacy. J Clin Oncol 27 (Suppl). (Abstr 551) Ryan PD, Tung NM, Isakoff SJ et al (2009) Neoadjuvant cisplatin and bevacizumab in triple negative breast cancer (TNBC): safety and efficacy. J Clin Oncol 27 (Suppl). (Abstr 551)
15.
go back to reference Burstein HJ, Elias AD, Rugo HS et al (2008) Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 26:1810–1816CrossRefPubMed Burstein HJ, Elias AD, Rugo HS et al (2008) Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 26:1810–1816CrossRefPubMed
16.
go back to reference Carey LA, Rugo HS, Marcom PK et al (2008) TBCRC 001: EGFR inhibition with cetuximab added to carboplatin in metastatic triple-negative (basal-like) breast cancer. J Clin Oncol 26 (Suppl). (Abstr 1009) Carey LA, Rugo HS, Marcom PK et al (2008) TBCRC 001: EGFR inhibition with cetuximab added to carboplatin in metastatic triple-negative (basal-like) breast cancer. J Clin Oncol 26 (Suppl). (Abstr 1009)
17.
go back to reference Ryden L, Jonsson PE, Chebil G et al (2005) Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up. Eur J Cancer 41(2):256–264CrossRefPubMed Ryden L, Jonsson PE, Chebil G et al (2005) Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up. Eur J Cancer 41(2):256–264CrossRefPubMed
18.
go back to reference Ryden L, Jirstrom K, Bendahl PO et al (2005) Tumor-specific expression of vascular endothelial growth factor receptor 2 but not vascular endothelial growth factor or human epidermal growth factor receptor 2 is associated with impaired response to adjuvant tamoxifen in premenopausal breast cancer. J Clin Oncol 23(21):4695–4704CrossRefPubMed Ryden L, Jirstrom K, Bendahl PO et al (2005) Tumor-specific expression of vascular endothelial growth factor receptor 2 but not vascular endothelial growth factor or human epidermal growth factor receptor 2 is associated with impaired response to adjuvant tamoxifen in premenopausal breast cancer. J Clin Oncol 23(21):4695–4704CrossRefPubMed
19.
go back to reference Ensinger C, Sterlacci W (2008) Implications of EGFR PharmDx™ Kit for cetuximab eligibility. Expert Rev Mol Diagn 8(2):141–148CrossRefPubMed Ensinger C, Sterlacci W (2008) Implications of EGFR PharmDx™ Kit for cetuximab eligibility. Expert Rev Mol Diagn 8(2):141–148CrossRefPubMed
20.
go back to reference Varella-Garcia M (2006) Stratification of non-small cell lung cancer patients for therapy with epidermal growth factor receptor inhibitors: the EGFR fluorescence in situ hybridization assay. Diagn Pathol 1:19CrossRefPubMed Varella-Garcia M (2006) Stratification of non-small cell lung cancer patients for therapy with epidermal growth factor receptor inhibitors: the EGFR fluorescence in situ hybridization assay. Diagn Pathol 1:19CrossRefPubMed
21.
go back to reference Hirsch FR, Varella-Garcia M, Cappuzzo F et al (2007) Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib. Ann Oncol 18(4):752–760CrossRefPubMed Hirsch FR, Varella-Garcia M, Cappuzzo F et al (2007) Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib. Ann Oncol 18(4):752–760CrossRefPubMed
22.
go back to reference Toyama T, Yamashita H, Kondo N et al (2008) Frequently increased epidermal growth factor receptor (EGFR) copy numbers and decreased BRCA1 mRNA expression in Japanese triple-negative breast cancers. BMC Cancer 8:309CrossRefPubMed Toyama T, Yamashita H, Kondo N et al (2008) Frequently increased epidermal growth factor receptor (EGFR) copy numbers and decreased BRCA1 mRNA expression in Japanese triple-negative breast cancers. BMC Cancer 8:309CrossRefPubMed
23.
go back to reference Schneider BP, Winer EP, Foulkes WD et al (2008) Triple-negative breast cancer: risk factors to potential targets. Clin Cancer Res 14(24):8010–8018CrossRefPubMed Schneider BP, Winer EP, Foulkes WD et al (2008) Triple-negative breast cancer: risk factors to potential targets. Clin Cancer Res 14(24):8010–8018CrossRefPubMed
24.
go back to reference Viale G, Rotmensz N, Maisonneve P et al (2009) Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity. Breast Cancer Res Treat 116(2):317–328CrossRefPubMed Viale G, Rotmensz N, Maisonneve P et al (2009) Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity. Breast Cancer Res Treat 116(2):317–328CrossRefPubMed
25.
go back to reference Hirsch FR, Herbst RS, Olsen C et al (2008) Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy. J Clin Oncol 26(20):3351–3357CrossRefPubMed Hirsch FR, Herbst RS, Olsen C et al (2008) Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy. J Clin Oncol 26(20):3351–3357CrossRefPubMed
26.
go back to reference Personeni N, Fieuws S, Piessevaux H et al (2008) Clinical usefulness of EGFR gene copy number as a predictive marker in colorectal cancer patients treated with cetuximab: a fluorescent in situ hybridization study. Clin Cancer Res 14(18):5869–5876CrossRefPubMed Personeni N, Fieuws S, Piessevaux H et al (2008) Clinical usefulness of EGFR gene copy number as a predictive marker in colorectal cancer patients treated with cetuximab: a fluorescent in situ hybridization study. Clin Cancer Res 14(18):5869–5876CrossRefPubMed
27.
go back to reference Puputti M, Tynninen O, Sihto H et al (2006) Amplification of KIT, PDGFRA, VEGFR2, and EGFR in Gliomas. Mol Cancer Res 4(12):927–934CrossRefPubMed Puputti M, Tynninen O, Sihto H et al (2006) Amplification of KIT, PDGFRA, VEGFR2, and EGFR in Gliomas. Mol Cancer Res 4(12):927–934CrossRefPubMed
Metadata
Title
Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up
Authors
Lisa Rydén
Karin Jirström
Monica Haglund
Olle Stål
Mårten Fernö
Publication date
01-04-2010
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-0758-6

Other articles of this Issue 2/2010

Breast Cancer Research and Treatment 2/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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