Abstract P3-07-35: Tumour immune subtyping as a predictive biomarker for adjuvant endocrine therapy in early breast cancer
Authors: Blok EJ , Engels CC , Jongste E , Dekker-Ensink G , Kroep JR , Kuppen PJK , van de Velde CJH 
Published: May 2016

Abstract
Adjuvant endocrine therapy is one of the mainstays in the treatment of breast cancer. Approximately 75% of all patients is treated with either tamoxifen or an aromatase inhibitor (AI), without any predictive biomarkers besides the estrogen receptor. It is known, that the immune system plays a pivotal role in the treatment of breast cancer. Earlier, subtyping the local immune response has been shown to predict therapy efficacy for chemotherapy. The current study was performed to discover predictive relations between the local immune response and survival in two different cohorts treated with adjuvant endocrine therapy.
Tumour tissue was collected from a cohort of 236 Dutch post-menopausal patients from the Intergroup Exemestane Study (IES-trial) who were randomized between 5 years of tamoxifen and 2.5 years of tamoxifen followed by 2.5 years of an AI (switch-scheme). The tumour tissue was stained for infiltration of CD8+ cytotoxic T-cells, FoxP3+ regulatory T-cells and CD68+ macrophages and the expression of different HLA-markers (classical HLA-I, HLA-E, HLA-G). These results were combined into three immune profiles (strong, intermediate, weak), and correlated to survival. Similar analyses were performed on a cohort of 2596 patients participating in the international TEAM trial, who were randomized between 2.5 years of tamoxifen followed by 2.5 years of an AI (switch scheme) and 5 years of an AI.
In the IES-cohort, patients with a strong local immune response had a significant better recurrence free survival when treated with 5 years of tamoxifen (5-year RFS 89.5%) compared to the switch scheme (5-year RFS 76.5%) (p=0.003). In patients with a weak local immune response, RFS was improved for patients treated with the switch scheme (5-year RFS 100%) compared to tamoxifen monotherapy (5-year RFS 75.6%) (P=0.003). Similar trends were observed for overall survival, although not statistically significant (p-values of 0.051 and 0.109 respectively). In the TEAM-cohort, no statistical significant differences were observed between both treatments in either immunological subtype (strong immune subtype: 5-year RFS 87.2% for 5-years AI versus 82.8% for the switch scheme (p=0.495), weak immune subtype: 85.9% for 5-year of AI vs 82.2% for the switch scheme (p=0.343)).
This study is the first to show combined immunological markers as a predictive marker for endocrine therapy. A strong immune response predicts a benefit for tamoxifen monotherapy, whereas a weak response predicts a benefit for AI-containing therapy. Although the exact mechanism of this effect is not known, we hypothesize that it might be contributed to immunomodulatory capacities of AIs. If the effect observed in the IES- cohort is indeed contributed to the effect of AIs, it would be expected that there is no difference in the TEAM-cohort between both arms since they both contain AIs, which was indeed observed. Future studies will be directed towards validation of these findings in an independent cohort.
Citation Format: Blok EJ, Engels CC, Jongste E, Dekker-Ensink G, Kroep JR, Kuppen PJK, van de Velde CJH. Tumour immune subtyping as a predictive biomarker for adjuvant endocrine therapy in early breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-35.