Abstract P4-08-03: EA2Clin: A novel immunohistochemical prognostic and predictive test for patients with estrogen receptor-Positive breast cancer

Abstract

Background: The majority of patients with early-stage estrogen receptor positive (ER+) breast cancer (BC) are treated with adjuvant endocrine therapy (ET) after primary surgery to reduce the risk of recurrence. A variety of tests are available to predict outcomes on ET but most require gene-level measurements and are expensive. Recently, we developed an immunohistochemistry (IHC) based test (EA2Clin) using levels of pre-treatment IL6ST together with clinical variables and on-treatment proliferation. The aim was to validate this test in cohorts of both pre- and post-menopausal women treated with two weeks of a variety of endocrine treatments (tamoxifen, fulvestrant or an aromatase inhibitor) prior to surgery. Methods: The cohorts are: (A) 186 post-menopausal women (PMW) with ER+ BC treated with at least 2 weeks of preoperative or neoadjuvant letrozole or anastrozole, then surgery followed by adjuvant letrozole (n=132) or tamoxifen (n=54); (B) 51 pre-menopausal women (preMW) with ER+ BC treated with 2 weeks of either neoadjuvant tamoxifen (n=24) or one 750mg dose of faslodex (n=27), then surgery followed by adjuvant tamoxifen. The median follow-up was 5.4 years for cohort A and 10.2 years for cohort B. IHC analysis was performed using a Leica BOND III autostainer and the EA2Clin algorithm was used to stratify patients in binary high or low-risk groups. Results: In the cohort of PMW, EA2Clin was highly significantly associated with both recurrence-free survival (RFS) (P<0.0001, HR=13.26, 95%CI=5.59-13.46) and breast cancer specific survival (BCSS) (P<0.0001, HR=12.93, 95%CI=4.43-37.72). The 5 and 10 year actuarial recurrence rates were 7%/22% and 46%/73% for the low and high risk groups, respectively. The actuarial breast cancer-related death rate for the low risk group was 5% at both 5 and 10 years, whereas for the high risk group was 33%/38%. Confounding factors were not found to be significant. In the cohort of preMW, our test was significantly associated with both RFS (P=0.002, HR=5.71, 95%CI=1.91-17.05) and BCSS (P=0.016, HR=4.81, 95%CI=1.34-17.26). The 5 and 10 year actuarial recurrence rates were 12%/29% and 27%/77% for the low and high risk groups, respectively. The 5 and 10 year actuarial breast cancer-related death rates were 7%/19% and 9%/58% for low and high risk groups, respectively. Discussion: · This study has validated EA2Clin as the first predictive tool to incorporate clinical data with pre and on-treatment immunohistochemical biomarkers to predict accurately the outcome of patients with ER positive breast cancer treated with adjuvant ET. · This test predicts both RFS and BCSS in pre- and PMW treated with a variety of endocrine agents. · Because this test incorporates clinical variables with simple IHC, it can be performed locally in any pathology lab. Citation Format: Turnbull AK, Fernando A, Renshaw L, Keys J, Thomas JS, Sims AH, Dixon JM. EA2Clin: A novel immunohistochemical prognostic and predictive test for patients with estrogen receptor-Positive breast cancer [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 P4-08-03.

The Signal Transducer IL6ST (gp130) as a Predictive and Prognostic Biomarker in Breast Cancer

“…Interestingly, EA2 (but not EA2clin) was shown to accurately predict outcome from adjuvant ET in both postmenopausal ( p = 0.001 and p = 0.016 for RFS and BCSS, respectively) and premenopausal women ( p = 0.002 and p = 0.016 for RFS and BCSS, respectively). EA2clin showed the best performance in postmenopausal patients, outperforming both EA2 and NPI and accurately predicting outcome ( p < 0.001 for both RFS and BCSS) regardless of the type of adjuvant ET received [ 53 ].…”