Abstract 1607: Pro-cancerous immune profile in primary breast tumors affects the timing and type of breast cancer recurrence
Authors: Takeshita Takashi , Yan Li , Takabe Kazuaki , Yamashita Hiroko 
Published: September 2020

Background: Tumor infiltrating lymphocytes (TILs) are immune cells that have migrated to the tumor tissue and the local microenvironment. Recently, evidence has emerged the presence of TILs affects the clinical outcomes of breast cancer patients. We hypothesize that immune cell infiltration profile of the primary tumors affects the timing and type of breast cancer recurrence. We evaluated the relationship between the timing and type of cancer recurrence and clinical factors, gene expression profiles, and immune cell infiltration profile utilizing two published large cohorts, TCGA and METABRIC.

Methods: 308 primary BCs in TCGA were analyzed and categorized as: recurrence ≤2 years (Early), between 2-5 years (Mid), recurrence &gt;5 years (Late), and no recurrence &gt;5 years (Survivors). 1,727 primary BCs in METABRIC were analyzed and categorized similarly: Early, Mid, Late, and Survivors, and further subdivided according to the type of recurrence (distant or local recurrence)

Results: We found that Early tumors demonstrated more aggressive clinical characteristics such as larger tumor, more lymph node metastases, higher pathological grades, higher Stages, and negative estrogen and progesterone receptors, compared with Survivors. On the other hand, no clinical characteristics of Late tumors were significantly different from Survivors, which implicate that clinical characteristics cannot distinguish late recurrence from Survivors. Utilizing pre-ranked gene set enrichment analyses, we showed that primary tumors of Survivors were associated with anti-cancer signaling such as interferon-α/-γ response and TNF-α signaling, compared with all recurrence groups. Furthermore, we found that host defense immunity (leukocyte fraction, lymphocyte infiltration, and macrophage fractions) was decreased in Late tumors compared with Survivors. Utilizing the CIBERSORT algorithm, we showed anti-cancer lymphocytes, memory CD4+ T cells and γδT cells, were significantly lower, and pro-cancerous regulatory T cells were significantly higher in Late tumors compared with Survivors. In distant recurrence analysis, we found that anti-cancer M1 macrophages were higher in Early and Mid compared to Survivors. Pro-cancerous regulatory T cells were significantly higher in Mid compared to Survivors. Interestingly, in local recurrence analysis, there was no statistically significant difference between timing of cancer recurrence and Survivors. Cytolytic activity score that assesses immune cell cytolytic activity was significantly lower in Late compared with Survivors, which suggest it to be a prognostic factor for Late recurrence.

Conclusions: We demonstrated that host defense immunity, pro-cancerous immune cells, and immune cell cytolytic activity in primary breast tumors affect the timing and type of breast cancer recurrence.

Citation Format: Takashi Takeshita, Li Yan, Kazuaki Takabe, Hiroko Yamashita. Pro-cancerous immune profile in primary breast tumors affects the timing and type of breast cancer recurrence [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1607.