Abstract P3-08-01: Prognostic performance of EndoPredict in invasive lobular carcinoma
Authors: Sestak I , Kronenwett R , Denkert C , Cuzick J , Dowsett M 
Published: February 2018

Background: Invasive lobular carcinomas (ILC) account for around 15% of all oestrogen receptor (ER) positive invasive breast cancers. The EndoPredict assay (EPclin) is a multigene classifier to predict the likelihood of distant recurrence in ER-positive, HER2-negative breast cancer patients treated with adjuvant endocrine therapy and has been validated in several retrospective translational studies. However, these validation studies did not include an analysis of the histological subtypes. Here, we investigate the role of EPclin for the prediction of distant recurrence in women with ILC and compare the prognostication to those with invasive ductal carcinoma (IDC) in TransATAC.

Methods: Data on EPclin and histological type of tumour were available for 928 postmenopausal women with ER-positive, HER2-negative disease treated with 5 years of tamoxifen or anastrozole. The primary endpoint was distant recurrence and the primary objective was to assess the prognostic value of EPclin for the prediction of distant recurrence in women with invasive lobular carcinoma. Kaplan–Meier and Cox regression analyses were used to determine distant recurrence risk for 0-10 years of follow-up. Likelihood ratio tests were used to assess the prognostic information provided by EPclin. Hazard Ratios (HR) are for a change in 1 Standard Deviation.

Results: 141 (15.2%) had ILC, 710 (76.5%) IDC, and the remaining 77 (8.3%) were of different histological type. EPclin provided highly significant prognostic value for distant recurrence in women with ILC (HR=3.33 (2.33-4.77), P&lt;0.001; LR-χ2=38.4). For those with IDC, EPclin was highly prognostic for distant recurrence over 10 years of follow-up (HR=2.41 (2.04-2.84), P&lt;0.001; LR-χ2=95.5). EPclin was more prognostic in IDC than ILC, and a significant interaction between EPclin and tumour type (ILC/IDC) was observed (P-interaction=0.038). 89 (63.1%) women with ILC were categorised into the low EPclin risk group and 52 (36.9%) into the high risk group. A highly significant separation between EPclin low and high risk groups was observed for ILC (10-year distant recurrence risk low: 6.2% (2.6-14.2) vs. high: 36.6% (24.2-52.1); HR=7.36 (2.71-20.01)). For women with IDC, 406 (57.2%) were categorised into the low risk group by EPclin and 304 (42.8%) were deemed high risk, with significant separation between risk groups (10-year distant recurrence risk low: 6.2% (4.1-9.3) vs. high: 28.5% (23.5-34.3); HR=5.59 (3.48-8.98)). We did not observe any differential efficacy of treatment between histological subtype and EPclin risk group.

Conclusions: This is the first analysis to focus on the role of EPclin for the prognostic assessment of women with ILC. Although numbers of women with ILC in TransATAC were small, EPclin provided highly significant prognostic information and risk stratification for this subgroup of women. 10-year distant recurrence risk in the EPclin low risk groups were similar between ILC and IDC, suggesting that chemotherapy is not indicated, irrespective of tumour type. Our results show that EPclin is informative in women with ILC.

Citation Format: Sestak I, Kronenwett R, Denkert C, Cuzick J, Dowsett M. Prognostic performance of EndoPredict in invasive lobular carcinoma [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-08-01.