Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer

Authors: Shinichiro Kashiwagi, Wakaba Fukushima, Yuka Asano, Wataru Goto, Koji Takada, Satoru Noda, Tsutomu Takashima, Naoyoshi Onoda, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira

Published in: BMC Cancer | Issue 1/2017

Login to get access

Abstract

Background

The recently developed reagent, eribulin mesylate (eribulin), is a microtubule dynamics inhibitor with a mechanism of action that differs from those of taxanes and vinca alkaloids. This drug is considered to be a promising chemotherapeutic agent for the treatment of locally advanced or metastatic breast cancer (MBC). In this study, we investigated if variables such as tumor expression of β-tubulin class III, glutathione S-transferase pi (GSTP) 1 or transducin-like enhancer of split (TLE) 3 might act as predictive factors on the therapeutic effect of eribulin chemotherapy.

Methods

The subjects included 52 patients with MBC who underwent chemotherapy with eribulin. The expression levels of Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor (HER) 2, Ki67, β-tubulin class III, GSTP-1 and TLE-3 were evaluated using immunostaining employing needle biopsy specimens.

Results

Patients with TLE3-negative tumors displayed significantly poorer outcomes regarding progression-free survival than patients with TLE3-positive tumors when prognosis within the group of patients with triple-negative breast cancer (TNBC) lesions was analyzed (p = 0.011, log-rank). In contrast, no such difference in prognosis was found in a comparison of TLE-3 positive/negative patients in the group of all patients (p = 0.433, log-rank) or of patients with non-TNBC lesions (p = 0.659, log-rank). Based on a univariate analysis of 22 TNBC cases, a better progression-free survival correlated significantly with a positive TLE3 expression in the tumor (p = 0.025). A multivariate logistic regression analysis including 22 patients with TNBC also showed that a positive TLE3 expression significantly correlated with a better progression-free survival (p = 0.037).

Conclusions

Our findings suggest that TLE3 is a useful marker for predicting the therapeutic effect of eribulin chemotherapy for TNBC.
Appendix
Available only for authorised users
Literature
1.
Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.CrossRefPubMed
2.
Abd El-Rehim DM, Ball G, Pinder SE, et al. 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. 2005;116:340–50.CrossRefPubMed
3.
Mattie MD, Benz CC, Bowers J, et al. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer. 2006;5:24.CrossRefPubMedPubMedCentral
4.
Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74.CrossRefPubMedPubMedCentral
5.
Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003;100:8418–23.CrossRefPubMedPubMedCentral
6.
Rakha EA, El-Rehim DA, Paish C, et al. Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance. Eur J Cancer. 2006;42:3149–56.CrossRefPubMed
7.
Bauer KR, Brown M, Cress RD, et al. 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. 2007;109:1721–8.CrossRefPubMed
8.
Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.CrossRefPubMed
9.
Bai RL, Paull KD, Herald CL, et al. Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data. J Biol Chem. 1991;266:15882–9.PubMed
10.
11.
Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004;4:253–65.CrossRefPubMed
12.
Kuznetsov G, Towle MJ, Cheng H, et al. Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389. Cancer Res. 2004;64:5760–6.CrossRefPubMed
13.
Jordan MA, Kamath K, Manna T, et al. The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther. 2005;4:1086–95.CrossRefPubMed
14.
Cortes J, O'Shaughnessy J, Loesch D, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377:914–23.CrossRefPubMed
15.
Okouneva T, Azarenko O, Wilson L, et al. Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase. Mol Cancer Ther. 2008;7:2003–11.CrossRefPubMedPubMedCentral
16.
Shon W, Jenkins SM, Ross DT, et al. Angiosarcoma: a study of 98 cases with immunohistochemical evaluation of TLE3, a recently described marker of potential taxane responsiveness. J Cutan Pathol. 2011;38:961–6.CrossRefPubMed
17.
Samimi G, Ring BZ, Ross DT, et al. TLE3 expression is associated with sensitivity to taxane treatment in ovarian carcinoma. Cancer Epidemiol Biomark Prev. 2012;21:273–9.CrossRef
18.
19.
Paradiso A, Mangia A, Chiriatti A et al. Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer. Ann Oncol 2005; 16 Suppl 4: iv14–19.
20.
Ferrandina G, Zannoni GF, Martinelli E, et al. Class III beta-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients. Clin Cancer Res. 2006;12:2774–9.CrossRefPubMed
21.
Mozzetti S, Ferlini C, Concolino P, et al. Class III beta-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin Cancer Res. 2005;11:298–305.PubMed
22.
Seve P, Dumontet C. Is class III beta-tubulin a predictive factor in patients receiving tubulin-binding agents? Lancet Oncol. 2008;9:168–75.CrossRefPubMed
23.
Miyake T, Nakayama T, Naoi Y, et al. GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer. Cancer Sci. 2012;103:913–20.CrossRefPubMed
24.
Miyagawa Y, Miyake T, Yanai A, et al. Association of body mass index with risk of luminal a but not luminal B estrogen receptor-positive and HER2-negative breast cancer for postmenopausal Japanese women. Breast Cancer. 2013;
25.
Kashiwagi S, Asano Y, Goto W, et al. Use of tumor-infiltrating lymphocytes (TILs) to predict the treatment response to eribulin chemotherapy in breast cancer. PLoS One. 2017;12:e0170634.CrossRefPubMedPubMedCentral
26.
Bogaerts J, Ford R, Sargent D, et al. Individual patient data analysis to assess modifications to the RECIST criteria. Eur J Cancer. 2009;45:248–60.CrossRefPubMed
27.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed
28.
Kashiwagi S, Yashiro M, Takashima T, et al. C-kit expression as a prognostic molecular marker in patients with basal-like breast cancer. Br J Surg. 2013;100:490–6.CrossRefPubMed
29.
Kashiwagi S, Yashiro M, Takashima T, et al. Advantages of adjuvant chemotherapy for patients with triple-negative breast cancer at stage II: usefulness of prognostic markers E-cadherin and Ki67. Breast Cancer Res. 2011;13:R122.CrossRefPubMedPubMedCentral
30.
Hirata J, Katsuno M, Kaneko S, et al. Clinical significance of human bone marrow stromal cell colonies in acute leukemias. Leuk Res. 1986;10:1441–5.CrossRefPubMed
31.
Twelves C, Cortes J, Vahdat LT, et al. Phase III trials of eribulin mesylate (E7389) in extensively pretreated patients with locally recurrent or metastatic breast cancer. Clin Breast Cancer. 2010;10:160–3.CrossRefPubMed
32.
McIntyre K, O'Shaughnessy J, Schwartzberg L, et al. Phase 2 study of eribulin mesylate as first-line therapy for locally recurrent or metastatic human epidermal growth factor receptor 2-negative breast cancer. Breast Cancer Res Treat. 2014;
33.
Mir O, Alexandre J, Tran A, et al. Relationship between GSTP1 Ile(105)Val polymorphism and docetaxel-induced peripheral neuropathy: clinical evidence of a role of oxidative stress in taxane toxicity. Ann Oncol. 2009;20:736–40.CrossRefPubMed
34.
35.
36.
Aogi K, Iwata H, Masuda N, et al. A phase II study of eribulin in Japanese patients with heavily pretreated metastatic breast cancer. Ann Oncol. 2012;23:1441–8.CrossRefPubMed
37.
Leon C, Lobe CG. Grg3, a murine Groucho-related gene, is expressed in the developing nervous system and in mesenchyme-induced epithelial structures. Dev Dyn. 1997;208:11–24.CrossRefPubMed
38.
Whitfield ML, Sherlock G, Saldanha AJ, et al. Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol Biol Cell. 2002;13:1977–2000.CrossRefPubMedPubMedCentral
39.
Androutsellis-Theotokis A, Leker RR, Soldner F, et al. Notch signalling regulates stem cell numbers in vitro and in vivo. Nature. 2006;442:823–6.CrossRefPubMed
40.
41.
Yoshida T, Ozawa Y, Kimura T, et al. Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states. Br J Cancer. 2014;110:1497–505.CrossRefPubMedPubMedCentral
Metadata
Title
Identification of predictive markers of the therapeutic effect of eribulin chemotherapy for locally advanced or metastatic breast cancer
Authors
Shinichiro Kashiwagi
Wakaba Fukushima
Yuka Asano
Wataru Goto
Koji Takada
Satoru Noda
Tsutomu Takashima
Naoyoshi Onoda
Masahiko Ohsawa
Kosei Hirakawa
Masaichi Ohira
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3598-5

Other articles of this Issue 1/2017

BMC Cancer 1/2017 Go to the issue

Research article

High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer

Research article

Strain elastography imaging for early detection and prediction of tumor response to concurrent chemo-radiotherapy in locally advanced cervical cancer: feasibility study

Study protocol

A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE)

Research article

Detection of circulating miRNAs: comparative analysis of extracellular vesicle-incorporated miRNAs and cell-free miRNAs in whole plasma of prostate cancer patients

Research article

Immunohistochemical evaluation of epithelial ovarian carcinomas identifies three different expression patterns of the MX35 antigen, NaPi2b

Research article

Meta-analysis comparing laparoscopic versus open resection for gastric gastrointestinal stromal tumors larger than 5 cm
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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
Image Credits