Abstract 2632: Identification of PTHrP as a biomarker of short survival & brain metastasis in a tissue microarray retrospective analysis of triple-negative breast cancer
Authors: Assaker Gloria , Camirand Anne , Abdulkarim Bassam , Omeroglu Atilla , Deschenes Jean , Kempen Leon Van , Kremer Richard , Sabri Siham 
Published: August 2018

Triple-negative breast cancer (TNBC) represents 10-20% of all BC cases, and is characterized by aggressive clinical course, frequent relapse, poor patient outcome, and lack of targeted therapy due to the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). Identifying TNBC molecular drivers and biomarkers would thus be highly beneficial to develop efficient targeted therapies. The parathyroid hormone-related protein (PTHrP) is known for its role in mammary gland and bone development, in addition to breast cancer progression. The aim of this study is to investigate the role of PTHrP as a potential prognostic biomarker in human TNBC.

We assessed PTHrP expression using immunohistochemical analysis of a tissue microarray (TMA) constructed for 523 patients newly diagnosed with TNBC between January 1998 and December 2008 in a single-center series with centralized ER, PR and HER-2 testing and standardized treatment and follow-up. We evaluated the correlation between PTHrP expression and TNBC patients' clinico-pathological features as well as progression and survival outcomes for a subset of 314 patients with available clinical data.

We show that PTHrP is overexpressed in 55.2% of TNBC tumors and high PTHrP expression is significantly associated with higher propensity for brain progression compared to other sites of distal progression (p=0.0458). Univariate analysis revealed that high PTHrP expression is significantly associated with decreased overall survival (OS) (p=0.0055), but not with progression-free survival (PFS) (p=0.1270). To further investigate the prognostic value of PTHrP with respect to different TNBC molecular subtypes, we analysed expression of markers known to stratify different TNBC subtypes. Multivariate analysis of PTHrP as an independent prognostic factor of survival with respect to different TNBC molecular subtypes is currently underway.

In conclusion, we provide for the first time evidence that increased PTHrP expression is significantly associated with shorter OS and higher propensity of brain progression in patients diagnosed with TNBC. Consequently, stratification of this disease based on PTHrP expression might identify patients with relatively higher risk of aggressive disease with brain progression. Additional studies investigating the role of PTHrP in organ-specific metastasis and using PTHrP-targeting strategies are warranted to improve the therapeutic outcome for patients diagnosed with TNBC.

Funding: Alberta Cancer Research Institute (ACRI) grant and Department of Defense (DoD, USA) Award No. W81XWH-15-1-0723

Citation Format: Gloria Assaker, Anne Camirand, Bassam Abdulkarim, Atilla Omeroglu, Jean Deschenes, Leon Van Kempen, Richard Kremer, Siham Sabri. Identification of PTHrP as a biomarker of short survival & brain metastasis in a tissue microarray retrospective analysis of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2632.