Inactivating mutations in 10 different genes in pathways critical to genomic integrity have been confirmed to be associated with inherited breast cancer in different ethnic groups [1]. We conducted a large-scale and systemic mutation analysis of BRCA1, BRCA2, p53, BRIP1, PALB2 and CHEK2 c.1100delC among 591 patients with early-onset (B35 years) breast cancer or affected relatives in China within 4 years, and the results contributed to the development of the genetic testing strategy in Chinese high-risk breast cancer families. All the included individuals were collected from six different medical centers located in southern and northern China, and were genetically independent ethnic Han Chinese. A total of 550 unrelated patients were analyzed for BRCA1 and BRCA2 mutations. The mutation frequency of BRCA1/2 in Chinese population was 9.45%, with 7.5% in early-onset and 13.4% in familial patients. When those patients with both early-onset breast cancer and affected relatives were concerned, the mutation frequency was up to 22.8%. We also observed that in patients with a family history of ovarian or gastric cancer, the incidence of BRCA1/2 mutation was about twice or more as that in patients without reporting the family history of these malignancies. The two recurrent BRCA1 mutations identified in our study, 1100delAT and 5589del8, accounted for 33.3% (8/24) of the deleterious mutations identified in BRCA1 gene, and haplotype analysis indicated that there might be some degree of shared ancestry for the two mutations in Chinese [2]. Among 240 non-BRCA1/2 patients without the phenotype of Li-Fraumeni syndrome (LFS) or Li-Fraumeni-like syndrome (LFL), we detected two novel germ line mutations (563T[C and 643_660del18) of p53, neither of which appeared in 768 normal controls. Functional assays revealed that they should be associated with the increasing risk of breast cancer [3]. PALB2 and BRIP1 have been recently identified as breast cancer susceptibility genes, which can colocalize with BRCA2 and BRCA1, respectively, at sites of DNA damage, and then contribute to their DNA repair function [1]. In our analysis, two truncating mutations of PALB2, 751C[T and 1050_1051delAAinsTCT, were identified in three independent patients with wild-type sequences at BRCA1 and BRCA2 (1% of the series), and that 751C[T was a recurrent mutation. We found that exon 4 accounted for 44.1% (15/34) of the person-times carrying any variant in PALB2 gene [4]. In BRIP1, we did not detect any protein-truncated mutation except a novel recurrent nonsynonymous variant (2971C[G, resulting in Q944E) [5]. Truncating allele 1100delC of CHEK2 has a frequency of 0.002-0.005 in northern Europe populations, but our results did not demonstrate the presence of CHEK2 c.1100delC among 114 studied patients [6]. At present, in view that much associated evidence in terms of the implications for breast cancer management in BRCA mutation carriers, current genetic testing still limits to BRCA genes, and there is growing evidence that BRCA mutation status may influence treatment recommendations [7]. Genetic testing for inherited breast cancer susceptibility has become a standard of care option for appropriately selected patients in the developed countries [8], while in China, little has been recognized. Recent trends show that A-Y. Cao Z. Hu Z.-M. Shao (&) Breast Cancer Institute, Cancer Hospital/Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong’an Road, 200032 Shanghai, People’s Republic of China e-mail: zhimingshao@yahoo.com