The Hypoxic Response Expression as a Survival Biomarkers in Treatment-Naive Advanced Breast Cancer.

Irwan Gunawan,Andi Asadul Islam,Andi Fachruddin Benyamin,Mochammad Hatta

doi:10.31557/apjcp.2020.21.3.629

Irwan Gunawan, Andi Asadul Islam + Show 2 more

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https://doi.org/10.31557/apjcp.2020.21.3.629

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Abstract

Objective:Hypoxia-associated biomarkers profiling may provide information for prognosis, staging, and subsequent therapy. We aim to evaluate whether the quantitative gene and protein expression of hypoxic response tumor markers — carbonic anhydrase IX (CAIX) and hypoxia- inducible factor 1 alpha (HIF1A) — may have a role in predicting survival in advanced breast cancer of Indonesian population. Methods:Tumor tissues and peripheral blood samples were collected from treatment - naïve locally advanced (LABC) or metastatic breast cancer patients (MBC) at Wahidin Sudirohusodo General Hospital (Makassar, South Sulawesi) and its referral network hospitals from July 2017 to March 2019. The level of mRNA (of blood and tumor tissue samples) and soluble protein (of blood samples) of CAIX and HIF1A were measured by RT-qPCR and ELISA methods, respectively, besides the standard histopathological grading and molecular subtype assessment. The CAIX and HIF1A expression, patients’ age, tumor characteristics, surgery status, and neoadjuvant chemotherapy drug classes were further involved in survival analyses for overall survival (OS) and progression-free survival (PFS). Results:Forty (30 LABC, 10 MBC) eligible patients examined were 21 hormone-receptors positives (15 Luminal A, 6 Luminal B) and 19 hormone-receptors negatives (10 HER2-enriched, 9 triple-negative). The CAIX blood mRNA and CAIX soluble protein levels in hormone-receptors negative patients were higher than in hormone-receptor-positive patients (p < 0.05). In univariate analysis, both CAIX and HIF1A levels predict OS (except HIF1A protein) with CAIX tissue mRNA has the highest hazard ratio (HR 8.04, 95%CI:2.45-26.39), but not PFS. Cox proportional hazard model confirmed that CAIX tissue mRNA is the independent predictor of OS (HR 6.10, 95%CI: 1.16-32.13) along with surgical status and tumor advancement type (LABC or MBC). Conclusions:CAIX mRNA expression of tumor tissue in treatment-naïve advanced breast cancer has a predictive value for OS.

Highlights

Breast cancer is leading cancer in females worldwide (Ferlay et al, 2015)
We aim to evaluate whether the quantitative gene and protein expression of hypoxic response tumor markers — carbonic anhydrase IX (CAIX) and hypoxia- inducible factor 1 alpha (HIF1A) — may have a role in predicting survival in advanced breast cancer of Indonesian population
The CAIX and HIF1A expression, patients’ age, tumor characteristics, surgery status, and neoadjuvant chemotherapy drug classes were further involved in survival analyses for overall survival (OS) and progression-free survival (PFS)

Summary

Introduction

Breast cancer is leading cancer in females worldwide (Ferlay et al, 2015). In the Asia-Pacific region, breast cancer incidence reached 18% of all cancers (Youlden et al, 2014). In Indonesia, breast cancer remains a national health burden, due to early peak age at presentation with large, aggressive tumors and more advanced stages (Ng et al, 2011; Wahidin et al, 2012). Breast cancer is characterized by heterogeneous clinicopathologic features and a wide epidemiological spectrum. Improving characterization of an individual’s prognosis in advanced breast cancer in Indonesian women potentially aid their clinical management, e.g., by providing adequate information to help with planning and identifying patients with worst risk who may choose to participate in novel investigational therapies

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