Translational relevance of androgen receptor immunohistochemistry scoring systems for data harmonization in triple negative breast cancer (TNBC).

Authors

null

Suhail Sayeed Mufti

HealthCare Global Enterprises Ltd, Bangalore, India

Suhail Sayeed Mufti , Bhanu Prakash Lalkota , Tejaswini BN , Hrishi Varayathu , Vinu Sarathy , Lalnun Puii , Lalram Sangi , Beulah Elsa Thomas , Diganta Hazarika , Satheesh Chiradoni Thungappa , Sriniivas Bj , Shekar Patil , Radheshyam Naik , Basavalinga Sadasivaiah Ajaikumar

Organizations

HealthCare Global Enterprises Ltd, Bangalore, India, Strand Life Sciences, Bengaluru, India, HealthCare Global Enterprises Limited, Bangalore, India, Healthcare Global Enterprises Ltd, 560027, India, Healthcare Global Enterprises Ltd, Bangalore, India, Health Care Global Enterprisese Ltd., India, HCG Bangalore Institute of Oncology, Bangalore, India, Health Care Global Enterprises Ltd., India

Research Funding

Pharmaceutical/Biotech Company
Astellas Pharma India Pvt. Ltd.

Background: Androgen receptor (AR) expressing triple negative breast cancer (TNBC) is a sub-set of TNBC with an evolving prognostic and predictive behaviour. AR immunohistochemical threshold for positivity has not been standardized and a wide range of cut-offs have been used across studies ( > 0% to 75%). In this study we explored AR immunohistochemistry thresholds in relation to disease free survival (DFS) and clinical outcomes in non-metastatic TNBC using the Allred and H-Score systems. Increasing interest in AR as a therapeutic target for TNBC and the use of digital tissue image analysis makes it important to standardize AR immunohistochemistry reporting. Methods: 100 FFPE (formalin-fixed paraffin-embedded) tumour blocks were retrieved for non-metastatic TNBCs diagnosed between January 2015 and May 2017 and immunostained using AR441 (IgG1) mouse monoclonal antibody. Clinical follow-up ranged from 59 to 31 months and DFS was calculated. Cut-off scores were explored using Evaluate Cutpoints (R maxstat package) and X-tile software. The score with maximum split in DFS (based on log-rank statistics and lowest p-value) was chosen as the cut-off. Descriptive and survival statistics was performed. Results: The median age was 51 (SD 11.262; range 28 to 82) years. Using Evaluate Cutpoints≥3 was found as the threshold for AR by Allred Score. 36% cases were AR positive using Allred score (HR 0.508; CI 0.234 - 1.11; p-value 0.08). Using Evaluate Cutpoints≥30 was found as the threshold for AR by H-Score (HR 0.624, CI 0.306 - 1.27; p-value 0.19). 35% cases were AR positive using H-Score. X-tile analysis also found the cut-offs as ≥3 and ≥30 for Allred and H-Score respectively (p < 0.05). A significant correlation was seen between the two scoring systems (Pearson Correlation 0.935; p < 0.01). A significantly higher number of grade III TNBCs were AR negative (n = 55/76) compared to grade II (n = 9/24) (p = 0.002). Cut-off for Ki67 was 75 (HR 1.61, CI 0.85-3.04, p-value 0.141) with a significantly higher number of AR negatives in the Ki67≥75 group (21/26; p < 0.05). The overall median DFS was 51.9 months. There was no significant difference in DFS for the AR negative (median: 47.4 months; mean: 39.39 months) and AR positive (Median survival not reached; mean: 41.3 months) groups(p = 0.23). Conclusions: AR immunohistochemistry cut-offs using the Allred (≥3) and H-Score (≥30) are close to the ones used for ER/PR immunohistochemistry as per ASCO/CAP guidelines, making a strong case for universal application of these systems for harmonization of AR data.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Breast Cancer—Metastatic

Track

Breast Cancer

Sub Track

Triple-Negative

Citation

J Clin Oncol 38: 2020 (suppl; abstr 1078)

DOI

10.1200/JCO.2020.38.15_suppl.1078

Abstract #

1078

Poster Bd #

163

Abstract Disclosures

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