Abstract PD3-01: Immune profile of small HER2+ tumors in the APT trial
Authors: Tolaney SM , Barry W , Guo H , Dillon D , Tan YB , Fuhrman K , Osmani W , Getz A , Baltay M , Dang C , Yardley D , Moy B , Marcom K , Krop I , Winer E 
Published: February 2018

Background: APT is a single arm multicenter, phase II study of paclitaxel and trastuzumab. Patients with HER2+ breast cancer with negative nodes and tumor size &lt; 3 cm were eligible. Disease-free survival at 7 years was 93.3% with only 4 distant recurrences. Characterizing intrinsic subtype and immune profiles of these smaller tumors may help us better understand if the biology of smaller HER2+ tumors is different than larger tumors that have been previously characterized.

Methods: Intrinsic subtyping by PAM50 and immune signatures by PanCancer Immune Profiling Panel were performed on the nCounter Analysis system on archival tissue. Tissue was also tested by immunohistochemistry for PDL1 (tumoral and immune cells) and was assessed for tumor infiltrating lymphocytes (TILs) using guidelines from the International TILs Working Group. TILS were categorized as follows: low (≤10%), intermediate (10-60%), high (≥60%); PD-L1 was characterized as low (0-1%), intermediate (1-10%), and high (&gt;10%).

Results: PAM50 data were available for 209 of the 406 cases: 142 (68%) were HER2-Enriched (HER2E), 22 (11%) Luminal A, 25 (12%) Luminal B, and 20 (10%) Basal-like. Immune profile information was available for 162 cases, of which 138 also had intrinsic subtype data. 184 cases were evaluated for PD-L1, and 210 cases for TILs. There was a strong correlation between PD-L1 in the tumor and lymphoid compartments (McNemar's chi-squared, p= 6.5x10-12). High tumoral PD-L1 was seen with higher frequency in the HER2E subset, while high immune cell PD-L1 and high TILs were seen with higher frequency within both the HER2E and Basal-like subtypes (Table). Immune profile data demonstrates that the T-cell signature has the strongest association with TILs, and that luminal A tumors tend to have very similar immune profiles while there is more variable expression of immune cell types with the basal-like tumors. Further work is ongoing to complete PAM50 and intrinsic subtype profiling of remaining tumors, and additional relationships between immune profile and intrinsic subtype will be presented at the meeting.

Conclusions: The majority of small HER2+ breast cancers are HER2E, and tumors of this intrinsic subtype have the highest prevalence of high expression of PDL1 and high TILs, suggesting that these tumors may be more immunogenic than the luminal A and B HER2+ tumors. Further work to explore immune profile data by intrinsic subtype is ongoing and may have implications for future trial design.

 HER2ELuminal ALuminal BBasal-LikePDL1 (tumoral)    Low6712159Intermediate16124High8100PDL1 (immune cell)    Low3712113Intermediate27154High26116TILs    Low6415165Intermediate36308High7011

Citation Format: Tolaney SM, Barry W, Guo H, Dillon D, Tan YB, Fuhrman K, Osmani W, Getz A, Baltay M, Dang C, Yardley D, Moy B, Marcom K, Krop I, Winer E. Immune profile of small HER2+ tumors in the APT trial [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 PD3-01.