Spectrum and characteristics of germline PALB2 pathogenic variants in 1556 early-onset breast cancer patients in China

Abstract Purpose Limited data are available regarding the partner and localizer of BRCA2 (PALB2) in Chinese patients with early breast cancer. This study aimed to assess the spectrum and characteristics of germline PALB2 pathogenic variants in this population. Methods Peripheral blood samples were collected from 1556 patients diagnosed with BRCA1/2 -negative early-onset breast cancer. All coding regions and exon‒intron boundaries of the PALB2 genes were screened through next-generation sequencing. Results The prevalence of PALB2 pathogenic variants was approximately 0. 77% in the cohort. Eleven PALB2 pathogenic variants were identified in twelve participants, including five frameshift mutations and six nonsense mutations. All other variants were detected once, except for PALB2 c. 1056₁057del (detected twice). Two PALB2 carriers (2/12, 16. 7%) have documented family history of breast cancer and/or ovarian cancer. Patients with a positive family history exhibited a threefold higher possibility of being identified as PALB2 carriers than those without a family history (2% vs. 0. 69%), although the difference was not statistically significant (p = 0. 178). Compared to non-carriers, PALB2 carriers has a tendency to appear in younger age (≤ 30 years) (25% vs 14. 4%), human epidermal growth factor receptor-2 (HER2) -negative status (83. 3% vs. 70. 2%), and diagnosed with invasive micropapillary carcinoma (16. 7% vs 3. 1%). Conclusion The prevalence of the germline PALB2 pathogenic variants was approximately 0. 77% in Chinese patients with BRCA1/2 -negative early-onset breast cancer. Our findings is crucial for understanding population-specific genetic risks and offering insights that can enhance genetic counseling and genetic testing strategies in this population.