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

person Jing Li Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China info_outline Jing Li, Peng He, Qindong Cai, Lili Chen, Yali Wang, Weifeng Cai, Yibin Qiu, Wenhui Guo, Minyan Chen, Yuxiang Lin, Chuan Wang, Fangmeng Fu

Authors person Jing Li Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China info_outline Jing Li, Peng He, Qindong Cai, Lili Chen, Yali Wang, Weifeng Cai, Yibin Qiu, Wenhui Guo, Minyan Chen, Yuxiang Lin, Chuan Wang, Fangmeng Fu Organizations Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China, Fujian Medical University Union Hospital, Fuzhou, Fujian, China Abstract Disclosures Research Funding Science Foundation of Fujian Province 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.1056_1057del, 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. Characteristic of the 12 patients with PALB2 pathogenic variants in this cohort. Dx FH with BC/OC Receptor Status Grade Histology Lymph nodes 35 None HER2-/ER-/PR- Ⅲ IDC Positive 38 None HER2-/ER+/PR+ Ⅱ MUC Negative 32 None HER2-/ER+/PR+ Ⅱ IDC Positive 35 None HER2-/ER+/PR+ Ⅲ IDC Positive 36 None HER2+/ER-/PR- unknown IDC Negative 40 Mother (BC) HER2-/ER+/PR+ Ⅱ IDC Positive 37 None HER2-/ER+/PR- Ⅱ IMPC Positive 29 None HER2-/ER+/PR+ Ⅲ IMPC Positive 29 None HER2+/ER-/PR- Ⅲ IDC Positive 30 An aunt (BC) HER2-/ER+/PR+ Ⅱ IDC Positive 32 None HER2-/ER+/PR+ Ⅱ IDC Negative 40 None HER2-/ER+/PR+ Ⅱ IDC Positive Dx: age at initial diagnosis of breast caner; FH: family history; BC: breast cancer; OC: ovarian cancer; HER2: human epidermal growth factor receptor-2; ER: hormone receptor; IDC: invasive ductal carcinoma; IMPC: invasive micropapillary carcinoma mix with invasive ductal carcinoma; MUC: mucinous carcinoma.