Prognostic value of endopredict for invasive lobular carcinomas in the combined ABCSG-6/8 and TransATAC trials
Authors: I. Sestak, M. Filipits, R. Buus, M. Rudas, M. Knauer, R. Kronenwett, J. Cuzick, M.I. Gnant, M. Dowsett, P. Dubsky
Journal: Annals of Oncology (2019)

Background: Invasive lobular carcinoma (ILC) accounts for approximately 15% of all breast cancer cases. Most of the correlations between multigene assays and patient outcome were derived from studies based on mixed cohorts with IDC and ILC. Here, we specifically investigate the prognostic value of Endopredict (EPclin) in a large cohort of ILCs pooled from large phase III randomised trials. Methods: A total of 2630 breast cancer patients with ER-positive, HER2-negative disease were included in this analysis. The primary objective of this analysis was to determine the prognostic value of EPclin for distant recurrence (DR) in years 0-10 in women with ILC. Secondary objectives included subgroup analysis and comparison of the prognostic value of EPclin in ILC vs. IDC. Results: 470 women (17.9%) presented with an ILC, 1944 (73.9%) with IDC, and 215 (8.2%) had other histological types. EPclin was highly prognostic in women with ILC (HR = 3.32 (2.54-4.34), P < 0.0001) and provided more prognostic value than clinicopathological parameters alone (HR = 2.17 (1.73-2.72), P < 0.0001) (added value: ΔLR-χ2=17.6). 298 women (63.4%) were categorised into the low EPclin risk group and they had a 10-year DR of 4.8% (2.7-8.4) compared to those 172 (36.6%) women in the high risk group with a 10-year DR risk of 26.6% (20.0-35.0) (HR = 6.33 (3.31-12.12), P < 0.0001). EPclin provided highly prognostic information in LN- (N = 326; HR = 2.56 (1.63-4.02)) and LN+ disease (N = 144; HR = 3.70 (2.49-5.50)). For women with IDC, EPclin categorised 59.1% of women into the low risk group and 40.9% into the high EPclin risk group (HR = 5.04 (3.67-6.90)). 17% fewer women were deemed high risk by EPclin if they had ILC vs. IDC. Conclusions: We present gene expression data and clinical outcome from the largest cohort of patients with ILC treated with adjuvant endocrine therapy in the absence of chemotherapy. EPclin provided highly significant prognostic value and significant risk stratification for women with ILC. 10-year DR risk in the EPclin low risk groups were similar between ILC and IDC, suggesting that chemotherapy in these low risk groups is not indicated, irrespective of tumour type. Our results suggest that histological subtyping is not indicated when interpreting EndoPredict. Legal entity responsible for the study: TransATAC and ABCSG Research Groups. Funding: Cancer Research UK. Disclosure: I. Sestak: Lecture fees: Myriad Genetics, NanoString. M. Knauer: Advisory board: Agendia, Genomic Health; Lecture fees: Agendia. R. Kronenwett: Inventor on the Endopredict patent; Employee, previous shareholder: Sividon. J. Cuzick: Research grants: AstraZeneca, Myriad Genetics, Memorial Sloan Kettering, Qiagen, Beckton Dickinson, Genera, Aventis Pharma; Honoraria: Merck, Roche, Qiagen, Myriad Genetics; Speaker's bureau: Beckton Dickinson/Hologic. M.I. Gnant: Honoraria: Amgen, AstraZeneca, Celgene, Eli Lilly, Invectys, Pfizer, NanoString, Novartis, Roche; Advisor board: AstraZeneca, Eli Lilly; Research grants: AstraZeneca, Novartis, Roche, Pfizer. M. Dowsett: Honoraria: Pfizer, Myriad Genetics, Roche; Consulting or advisory role: Roche/Genentech, GTx, Radius Health; Research funding (Inst): AstraZeneca, Novartis, Pfizer, Radius Health. P. Dubsky: Grant support: Agendia, Sividon, Myriad Genetics, NanoString; Advisory role: Amgen; Speaker's fee: Myriad Genetics, Sividon, Amgen. All other authors have declared no conflicts of interest.