Spectrum and characteristics of germline PALB2 pathogenic variants among patients with early-onset breast cancer in China.

e22536 Background: Partner and localizer of BRCA2 (PALB2) plays a critical role in homologous recombination repair and recognized as a breast cancer predisposition gene. Early age at onset of breast cancer is considered a hereditary high-risk factor. However, limited information is available about early-onset breast cancer in China. The objective of this study was to investigate the spectrum and characteristics of germline PALB2 pathogenic variants among this population. Methods: A total of 1556 patients with BRCA1/2-negative early-onset breast cancer were included. Peripheral blood samples were collected and all coding regions and exon‒intron boundaries of the PALB2 genes were screened through next-generation sequencing. Results: The prevalence of germline PALB2 pathogenic variants was approximatel 0. 77% in entire cohort. Eleven PALB2 pathogenic variants were identified in twelve participants, including five frameshift mutations, four nonsense mutations and one missense mutation. Except for PALB2 c. 1056₁057del, which was detected twice, all other variants were detected once. In comparison to non-carriers, PALB2 carriers were more likely to be 30 years old or younger (25% vs. 14. 4%), have a positive family history of breast or ovarian cancer (16. 7% vs. 6. 3%), exhibit metastatic lymph nodes (75% vs. 50. 9%), belong to human epidermal growth factor receptor-2 (HER2) -negative and hormone receptor (HR) - positive subtype (75% vs 54. 2%), and diagnosed with invasive micropapillary carcinoma (16. 7% vs 3. 1%). Conclusions: The prevalence of the germline PALB2 pathogenic variants is approximately 0. 77% in BRCA1/2 mutation-negative early-onset breast cancer patients in China. Our findings contribute additional insights into the spectrum and characteristics of PALB2 pathogenic variants in Chinese early-onset breast cancer patients, providing valuable information for this population. Key words: PALB2, Germline mutation, Genetic sequencing, early-onset breast cancer, China. Table: see text