High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia

In East Asia, the breast cancer incidence rate among women aged <50 years has rapidly increased. Emerging tumors are distinctly characterized by a high prevalence of estrogen receptor (ER)-positive/human epidermal growth factor receptor (HER2)-negative cancer. In the present study, we identified unique genetic alterations in these emerging tumors. We analyzed gene copy number variations (CNVs) in breast tumors from 120 Taiwanese patients, and obtained public datasets of CNV and gene expression (GE). The data regarding CNV and GE were separately compared between East Asian and Western patients, and the overlapping genes identified in the comparisons were explored to identify the gene-gene interaction networks. In the age <50 years/ER + /HER2- subgroup, tumors of East Asian patients exhibited a higher frequency of copy number loss in APOA1/C3/A4/A5, a lipid-metabolizing gene cluster (33 vs. 10%, P < .001) and lower APOA1/C3/A4/A5 expressions than tumors of Western patients. These copy number loss related- and GE-related results were validated in another Taiwanese cohort and in two GE datasets, respectively. The copy number loss was significantly associated with poor survival among Western patients, but not among East Asian patients. Lower APOAT, APOC3, and APOA5 expressions were associated with higher ESTIMATE immune scores, indicating an abundance of tumorinfiltrating immune cells. In conclusion, APOA1/C3/A4/A5 copy number loss was more prevalent in luminal breast tumors among East Asian women aged <50 years, and its immunomodulatory effect on the tumor microenvironment possibly plays various roles in the tumor biology of East Asian patients.