Abstract P1-04-11: Tumor Infiltrating Lymphocytes in initial HER2-Low breast cancer
Authors: Fernandes Italo , Damasceno Eduarda , Kaliks Rafael , Corpa Marcus , Schvartsman Gustavo 
Published: March 2023

Rationale Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer (BC) represents a distinct subgroup of patients (pts) that derives significant benefits from anti-HER2 therapy. More recently, patients with metastatic BC that were previously considered HER2-Negative but with low positivity by immunohistochemistry (IHC) and a negative in situ hybridization (ISH) (HER2 1+, or 2+ with negative ISH) derived benefit from treatment with trastuzumab-deruxtecan (T-Dxd), an antibody-drug conjugate that targets HER2 receptor. This novel subgroup, termed HER2-Low (H-Low), represents nearly 60% of BCs. Tumor infiltrating-lymphocytes (TILs) are a biomarker that can be easily analyzed without additional stains, and that tend to be higher in tumors with more aggressive features. High levels of TILs can predict better outcomes in triple-negative (TN) and HER2-Positive (H-Pos) tumors. To date, there is no information about TILs levels in H-Low tumors. Objectives This work aims to determine TILs levels in HER2-Low tumors and their correlation with clinicopathologic features. Methods We retrospectively analyzed tissue from breast surgical products in a tertiary hospital in Sao Paulo, Brazil, from January 2021 to March 2022. Inclusion criteria were stage I to III invasive BC and available data for TILs, HER2, estrogen receptor (ER), progesterone receptor (PR) by IHC, and ISH, when applicable. Exclusion criteria was neoadjuvant therapy. We extracted clinical, histopathologic, and IHC parameters. HER2 subtypes were defined as follows: HER2-Negative (H-Neg) when HER2 0+ in IHC; H-Low when IHC 1+, or 2+ with ISH negative; and H-Pos when IHC 3+ or 2+ with ISH positive. TILs were defined as absent (0), low (1 to 9%), intermediate (10 to 39%) and high (&gt;40%). Ki-67 levels were divided as low (up to 19%) and high (≥20%). Results We included 202 eligible pts. 128 were H-Neg, 51 were H-Low (35 IHC 1+ and 16 IHC 2+ with ISH negative), and 23 were H-Pos. Four pts were TN in H-Neg and none in H-Low group. The mean ages for H-Neg, H-Low and H-Pos were 57, 51, and 57 years, respectively. ER and PR were negative in 3.1% and 11.7% of H-Neg, 0 and 7.8% of H-Low, and 52.4% and 56.5% of H-Pos. Ki-67 levels were high in 27.3% of H-Neg, 31.4% of H-Low and 82.6% of H-Pos. Nodal stages and multifocality were similar. Ductal histology had 89 (69.5%), 45 (88.2%), and 21 (91.3%) cases for H-Neg, H-Low, and H-Pos. Lobular carcinoma was found in 30 (23,4%) in H-Neg, 4 (7.8%) in H-Low, and none in the H-Pos group. Nuclear grade (NG) 2 was seen in 64.8% of H-Neg and 62% of H-Low. Nuclear grade 3 seen was in 82.6% of H-Pos. Histologic grade 1 was present in H-Neg and H-Low, with 29.7% and 25.5%; grade 2 was seen in 56.3% and 56.9%, respectively. In H-Pos grade 3 was found in 47.8%. Angiolymphatic invasion and perineural invasion were present in 26.6%, 35.3%, and 17.4%; and 26.6%, 35.3%, and 13% of H-Neg, H-Low and H-Pos respectively. TILs in H-Neg, H-Low, and H-Pos were, respectively, absent in 16.4%, 17.6%, and 8.7%; low in 69.5%, 52.9% and 34.8%; intermediate in 11.7%, 25.5% and 47.8%; and high in 2.3%, 3.9% and 8.7%. We divided samples into TILs levels to look at the distribution of HER2 subtypes. Absent, low, intermediate, and high TILs had respectively 32, 124, 39, and 7 cases. There were more H-Neg in low TILs and H-Pos in high TILs, with, respectively, 65.6% and 6.3% of absent; 71.8% and 6.5% of low; 38.5% and 28.2% of intermediate; and 42.9% and 28.6% of high TILs. Conversely, H-Low showed stability among the groups, with 28.1%, 21.8%, 33.3%, and 28.6% in absent, low, intermediate, and high TILs, respectively. Complete data and statistical analysis will be presented at the meeting. Conclusion TILs in H-Low are similar to H-Neg. Both had lower TILs compared to H-Pos pts. In our study, only 25% were defined as H-Low, which demonstrates that a better comprehension about prevalence or pathology concordance between HER2 IHC 0 and 1+ is warranted. TILs may not play a role as a biomarker in H-Low tumors.

Citation Format: Italo Fernandes, Eduarda Damasceno, Rafael Kaliks, Marcus Corpa, Gustavo Schvartsman. Tumor Infiltrating Lymphocytes in initial HER2-Low breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-04-11.