Abstract P3-06-06: Prediction of benefit from endocrine therapy in ER+ early stage breast cancer: Correlative studies of the breast cancer index HoxB13/IL17BR (H/I) ratio, ER, PR, and HER2 expression in the randomized Stockholm trial
Authors: Zhang Yi , Schroeder Brock E , Jerevall Jannok Piiha-Lotta , Fornander Tommy , Stal Olle , Schnabel Catherine A , Sgroi Dennis C 
Published: May 2015

Background: Hormone receptor expression is an indication for endocrine therapy, however, receptor status is insufficient to account for the considerable heterogeneity of response, and additional predictive biomarkers are needed. The HoxB13/IL17BR (H/I) gene expression ratio has previously been shown to be predictive of benefit from extended endocrine therapy for women with estrogen receptor-positive (ER+) breast cancer treated in the MA.17 trial. In this correlative study, H/I was compared with ER, PR, and HER2 expression in assessing response to adjuvant tamoxifen (TAM) versus untreated (UNT) in ER+, node-negative patients from the prospective, randomized Stockholm trial.

Methods: Analysis included 600 ER+, LN- patients (317 TAM, 283 untreated) from the Stockholm cohort. Expression profiles were generated by RT-PCR for H/I, ER, PR, and HER2, with additional IHC studies for ER, PR, and HER2. Multivariate Cox models including age, tumor size and tumor grade, were used to assess the significance of the interaction between treatment and each biomarker as continuous variables. 10-year risk of distant recurrence, as a function of each continuous biomarker, was estimated from Cox model in each of the 2 treatment arms.

Results: The interaction between H/I and TAM treatment was significant (p = 0.003). Consistent with the significant interaction, the 10-year rate of distant recurrence as a function of continuous H/I demonstrated that the reduction in recurrence rates with TAM correlated with increasing H/I. Interaction P values for all other biomarkers were nonsignificant [ER (PCR), P=0.473; ER (IHC), p=0.371; PR (PCR), p=0.555; PR (IHC), p=0.475; HER2 (PCR), p=0.947, and HER2 (IHC), p=0.839]. The treatment effect of tamoxifen was unchanged across ER, PR, and HER2 expression levels.

Conclusions: Results of this study provide further support for HoxB13/IL17BR as a biomarker of endocrine response. The H/I gene expression ratio, but not ER, PR, or HER2 expression evaluated as continuous variables, was predictive of benefit from adjuvant TAM treatment. Findings indicate that H/I endocrine response activity is not strictly correlated with ER+ expression and provides independent predictive information regarding estrogen signaling-driven recurrences.

Citation Format: Yi Zhang, Brock E Schroeder, Piiha-Lotta Jerevall Jannok, Tommy Fornander, Olle Stal, Catherine A Schnabel, Dennis C Sgroi. Prediction of benefit from endocrine therapy in ER+ early stage breast cancer: Correlative studies of the breast cancer index HoxB13/IL17BR (H/I) ratio, ER, PR, and HER2 expression in the randomized Stockholm trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-06.