Prognostic value of androgen receptor expression in triple negative breast carcinomas: personal experience and comments on a review about "Triple-negative breast cancer: treatment challenges and solutions" by Collignon et al

(1)

© 2016 Ieni et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).

Breast Cancer - Targets and Therapy 2016:8 157–159

Breast Cancer - Targets and Therapy

Dove

press

submit your manuscript | www.dovepress.com

Dovepress 157

L E T T E R

open access to scientific and medical research Open Access Full Text Article

http://dx.doi.org/10.2147/BCTT.S113577

Prognostic value of androgen receptor expression

in triple negative breast carcinomas: personal

experience and comments on a review about

“Triple-negative breast cancer: treatment

challenges and solutions” by Collignon et al

Antonio Ieni1

Valeria Barresi1

Giuseppina Rosaria Rita Ricciardi2

Barbara Adamo3

Vincenzo Adamo2

Giovanni Tuccari1

1_{Department of Human Pathology of}

Adult and Evolutive Age “Gaetano Barresi”, Section of Pathology, University of Messina, AOU “Policlinico G Martino”; 2_Medical

Oncology Unit AOOR Papardo-Piemonte, Department of Human Pathology of Adult And Evolutive Age “Gaetano Barresi”, University of Messina, Messina, Italy; 3_Medical

Oncology Hospital Clinic, Barcelona, Spain

Dear editor

Recently, we read with great interest the review by Collignon et al entitled

“Triple-negative breast cancer: treatment challenges and solutions”,1_{which appeared in the}

last issue of Breast Cancer: Targets and Therapy. In this article, the authors extensively reviewed studies concerning the opportunity to identify triple negative breast carcinoma (TNBC) subtypes by newly proposed markers, taking into account their biological heterogeneity on the light of clinical implications.

It is well known that TNBC represents ~15% of all breast cancers and they are distinguished by the lack of expression of the estrogen and progesterone receptor using immunohistochemistry (IHC) and by the lack of overexpression and/or

ampli-fication of HER2 obtained using IHC and/or fluorescence in situ hybridization.1_The

clinicopathological characteristics of this subtype include tumors of large size, highly undifferentiated, high proliferative index, central necrosis, multiple apoptotic cells, and high-positive lymph nodes.

However, utilizing gene expression profiling of TNBC, a luminal androgen receptor

subtype has been identified among others.2_{Moreover, a recent systematic meta-analysis}

of 19 different studies showed that the expression of androgen receptor (AR) is a favor-able prognostic marker, providing the rationale for the development of a Phase II study with bicalutamide, a nonsteroidal antiandrogen in the treatment of metastatic TNBC-AR

positive (NCT00468715).3_{In relation to this hypothesized role of AR, we would report}

herein our previous immunohistochemical experience in a cohort of TNBC.4_{In detail,}

we have found AR immunopositivity (IHC >10%) in 26.6% of TNBC cases; moreover,

both univariate and multivariate analyses showed that AR is significantly associated with

overall survival, representing an independent variable able to identify a TNBC subtype.4

These data further confirm the significantly positive correlation between AR expression and favorable survival in TNBC patients since higher AR expression predicted a better

relapse-free survival in patients with chemoresistant TNBC, as reported elsewhere.5

In light of the abovementioned studies, we fully agree with the suggestion of

Collignon et al1_{regarding the block of AR pathway as promising approach in the}

Correspondence: Giovanni Tuccari Department of Human Pathology of Adult and Evolutive Age “Gaetano Barresi”, Azienda Ospedaliera Universitaria “Policlinico G Martino” - pad. D, Via Consolare Valeria, 1, 98125 Messina, Italy

Tel +39 90 221 2539 Fax +39 90 292 8150 Email tuccari@unime.it

Journal name: Breast Cancer - Targets and Therapy Article Designation: LETTER

Year: 2016 Volume: 8

Running head verso: Ieni et al

Running head recto: Prognostic value of AR expression in TNBC DOI: http://dx.doi.org/10.2147/BCTT.S113577

Breast Cancer: Targets and Therapy downloaded from https://www.dovepress.com/ by 192.167.105.229 on 12-Sep-2016

For personal use only.

Powered by TCPDF (www.tcpdf.org)

1 / 1

This article was published in the following Dove Press journal: Breast Cancer - Targets and Therapy

19 August 2016

(2)

Breast Cancer - Targets and Therapy 2016:8

submit your manuscript | www.dovepress.com

Dovepress

158

Ieni et al

treatment of patients with the luminal AR subtype of TNBC.

In fact, this new targeted therapy shows potential advantages,6

although more additional studies are needed to be validated in order to acquire a prognostic/predictive significance of AR in TNBC. However, the documented inverse correlation between low AR expression and high Ki67 rate has been significantly correlated with a shorter overall survival and

a more aggressive disease in TNBC.4_{Therefore, our data}

suggest that an immunohistochemical tissue approach by the combination of AR expression and Ki-67 status might be a useful prognostic marker in TNBC in order to subclassify the risk of these patients.

Disclosure

The authors report no conflicts of interest in this communication.

References

1. Collignon J, Lousberg L, Schroeder H, Jerusalem G. Triple-negative breast cancer: treatment challenges and solutions. Breast Cancer: Targets

and Therapy. 2016;8:93–107.

2. Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–2767.

3. Gucalp A, Tolaney S, Isakoff SJ, et al; Translational Breast Cancer Research Consortium (TBCRC 011). Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clin Cancer Res. 2013;19(19):5505–5512. 4. Ricciardi GR, Adamo B, Ieni A, et al. Androgen receptor (AR),

E-cad-herin, and Ki-67 as emerging targets and novel prognostic markers in triple-negative breast cancer (TNBC) patients. PLoS One. 2015;3(6): e0128368.

5. Yu KD, Zhu R, Zhan M, et al. Identification of prognosis-relevant sub-groups in patients with chemoresistant triple-negative breast cancer. Clin

Cancer Res. 2013;19(10):2723–2733.

6. Anestis A, Karamouzis MV, Dalagiorgou G, Papavassiliou AG. Is andro-gen receptor targeting an emerging treatment strategy for triple negative breast cancer? Cancer Treat Rev. 2015;41(6):547–553.

(3)

Breast Cancer - Targets and Therapy 2016:8 submit your manuscript | www.dovepress.com

Dovepress

Breast Cancer - Targets and Therapy

Publish your work in this journal

Submit your manuscript here: https://www.dovepress.com/breast-cancer---targets-and-therapy-journal

Breast Cancer - Targets and Therapy is an international, peer- reviewed open access journal focusing on breast cancer research, identification of therapeutic targets and the optimal use of preven-tative and integrated treatment interventions to achieve improved outcomes, enhanced survival and quality of life for the cancer patient.

The manuscript management system is completely online and includes a very quick and fair peer-review system, which is all easy to use. Visit http://www.dovepress.com/testimonials.php to read real quotes from published authors.

Dove

press

159

Prognostic value of AR expression in TNBC

Authors’ reply

Joëlle Collignon1

Laurence Lousberg1

Hélène Schroeder1

Guy Jerusalem1,2

1_{Medical Oncology Department, CHU Sart Tilman Liege, Domaine}

Universitaire du Sart Tilman, 2_{University of Liege, Liege, Belgium}

Correspondence: Guy Jerusalem

Medical Oncology, Domaine Universitaire du Sart Tilman, Bâtiment B35, Liège 4000, Belgium

Tel +32 4 366 7111

Email g.jerusalem@chu.ulg.ac.be

Dear editor

Thank you for having shared with us your interesting experi-ence concerning the determination of the androgen receptor status, the inverse correlation between KI67 and androgen receptor expression, and the potential prognostic implica-tions. Your results are in line with previous work published

in this field and further highlights that additional research in this subgroup of triple negative breast cancer is definitively needed. In particular, we hope that specific treatments will allow us to do a major step forward in the treatment of a subgroup of patients presenting with triple negative breast cancer. Unfortunately, the results currently available with antiandrogen therapy, although promising, represent rather a very small step forward. Further research is also needed in order to evaluate if standard immunohistochemistry techniques can be an alternative to androgen-related gene signatures for the identification of patients presenting better outcome after antiandrogen therapy.

Disclosure

GJ has received honoraria from Amgen, Pfizer, Novartis, Roche, and Celgene and research grants from Novartis, Roche, and MSD. The authors report no other conflicts of interest in this communication.

Dove Medical Press encourages responsible, free and frank academic debate. The content of the Breast Cancer: Targets and Therapy ‘letters to the editor’ section does not necessarily represent the views of Dove Medical Press, its officers, agents, employees, related entities or the Breast Cancer: Targets and Therapy editors. While all reasonable steps have been taken to confirm the content of each letter, Dove Medical Press accepts no liability in respect of the content of any letter, nor is it responsible for the content and accuracy of any letter to the editor.