High tumor copy number variations burden was associated with poor prognosis in patients with endocrine-resistant breast cancer

Abstract Background Several studies have showed alterations in genes were associated with endocrine resistance in breast cancer. Nevertheless, genomic characteristics in primary endocrine-resistant breast cancer has not been thoroughly reported. Whether the genomic landscape of primary endocrine-resistant breast cancer is different from that of secondary endocrine-resistant breast cancer is unknown. Methods We analyzed the genomic landscape of primary tumor of consecutive patients with hormonal-receptor positive breast cancer that were genetically profiled by next generation sequencing using a 425 cancer-related genes panel in real-world clinical practice in our center between September, 2019 to December, 2020. According to the duration of endocrine treatment, we classified them into primary endocrine resistance group and secondary endocrine resistance group. Frequency of altered genes was compared between groups. Results A total of 41 tumor samples of which 25 cases in primary endocrine resistance and 16 cases in secondary endocrine resistance with same testing gene panel were included for analysis. TP53 (65.9%, 27/41), PIK3CA (46.3%, 19/41), MYC (36.6%, 15/41), MCL1 (31.7%, 13/41), CCND1 (31.7%, 13/41) were the most frequently altered genes in all 41 BCs. Copy number amplification of MYC was common in primary endocrine resistant group (48.0%), while with lower frequency in secondary endocrine resistant group (18.8%, P = 0.058). Copy number variation (CNV) of CCND1, MCL1, FGF19, ZNF217, ZNF703 and FGFR1 were commonly observed in primary endocrine resistance group. Percentage of CNVs in all variation types was significantly higher in primary endocrine resistance group than that in secondary resistance group (33.0% vs. 21.0%, P = 0.030). We further analyzed and found patients with more than 5 CNV events in the primary tumor, which we defined as high tumor CNVs burden, was associated with the poorer prognosis. Conclusion Copy number alterations were more commonly seen in primary endocrine-resistant breast cancer and high CNVs burden was associated with poor prognosis in patients with ER + breast cancer. This finding urged to further investigate the prognostic value of CNVs burden in patients with ER + breast cancer who receive endocrine therapy.