Abstract P1-09-09: Octogenerian breast cancer was associated with higher infiltration of M2 macrophages and tregs and worse disease free survival

Abstract

Abstract Backgrounds: It is known that elderly patients have worse prognosis of breast cancer and commonly the blame is on their medical comorbidities and access to care. We question this dogma and hypothesized that extreme elderly (octogenerians over 80 years old) have biologically worse cancer that can be defined by mutation load, tumor heterogeneity, and its tumor immune microenvironment. Patients and Methods: Two groups; Control (patients aged 40-65), and octogenerians (age over 80) at the time of breast cancer diagnosis were compared in The Cancer Genomic Atlas (TCGA; n=1093) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=2506) cohorts. Cytolytic activity score (CYT), CIBERSORT analysis, tumor mutation load, as well as mutant-allele tumor heterogeneity (MATH) score were conducted as previously published. Results: The total number of patients in the control group and octogenarians were 675 and 54 in TCGA, and 1001 and 121 in METABRIC, respectively. Octogenerians had significantly worse disease free survival in addition to overall survival in both cohorts (p<0.01 in both), which suggested that they had worse cancer biology. In terms of subtypes, octogenerians had significantly higher rate of ER positive cancers than control group in both cohorts (75.3% vs 87.0%, p<0.01 in TCGA, 72.9% vs 90.0%, p<0.01 in METABRIC), but there was no significant deference in PgR or Her2 positivity. With regard of PAM50 classification, luminal-A and B subtypes were significantly higher in octogenarians (44.6% vs 34.7%, 31.4% vs 20.5%, respectively, p<0.01), whereas basal (7.4% vs 11.2%) and claudin-low (2.5% vs 11.8%) subtypes were significantly lower (p<0.05) in octogenarians in METBRIC cohort. Given that octogenerians had subtype with favorable prognosis, we examined whether they had higher mutation load or heterogeneity of the tumor. There were no significant difference in tumor mutation load and MATH score that reflect tumor heterogeneity in both cohorts. On the other hand, breast tumors of octogenerians were significantly associated with immune-suppressive cells, such as M2 type macrophages and regulatory T cells in both cohorts (p<0.05), whereas they were negatively associated with immune- eliminating cells, such as activated memory CD4 T-cells and M1 type of macrophages in METABRIC cohort (p<0.05). There was no significant difference in CYT in TCGA cohort. Conclusion: Our result demonstrated that octogenerians breast tumors were infiltrated with more immune-suppressive cells that may contribute to their biologically worse behavior. Citation Format: Okano M, Elkhanany A, Qi Q, Yan L, Takabe K. Octogenerian breast cancer was associated with higher infiltration of M2 macrophages and tregs and worse disease free survival [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-09.