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With the development of poly (ADP-ribose) polymerase inhibitors for treatment of patients with cancer with an alteredIn this study, we built a new model (Asian Risk Calculator) for estimating the likelihood of carrying a pathogenic variant inAsian Risk Calculator included age of diagnosis, ethnicity, bilateral breast cancer, tumor biomarkers, and family history of breast cancer or ovarian cancer as predictors. The inclusion of tumor grade improved significantly the model performance. The full model was calibrated (Hosmer-LemeshowPopulation-specific customization of mutation prediction models and clinical genetic testing criteria improved the accuracy of BRCA mutation prediction in Asian patients.

Mammographic density is a measurable and modifiable biomarker that is strongly and independently associated with breast cancer risk. Paradoxically, although Asian women have lower risk of breast cancer, studies of minority Asian women in predominantly Caucasian populations have found that Asian women have higher percent density. In this cross-sectional study, we compared the distribution of mammographic density for a matched cohort of Asian women from Malaysia and Caucasian women from Sweden, and determined if variations in mammographic density could be attributed to population differences in breast cancer risk factors.Volumetric mammographic density was compared for 1501 Malaysian and 4501 Swedish healthy women, matched on age and body mass index. We used multivariable log-linear regression to determine the risk factors associated with mammographic density and mediation analysis to identify factors that account for differences in mammographic density between the two cohorts.Compared to Caucasian women, percent density was 2.0% higher among Asian women (p 0.001), and dense volume was 5.7 cmOur analysis suggests that among post-menopausal women, population differences in mammographic density and risk to breast cancer may be accounted for by height, weight, and parity. Given that pre-menopausal Asian and Caucasian women have similar population risk to breast cancer but different dense volume, development of more appropriate biomarkers of risk in pre-menopausal women is required.

Background APOBEC3B is a cytosine deaminase implicated in immune response to viral infection, cancer predisposition and carcinogenesis. Germline APOBEC3B deletion is more common in East Asian women and confers a modest risk to breast cancer in both East Asian and Caucasian women. Analysis of tumour samples from women of European descent has shown that germline APOBEC3B deletion is associated with an increased propensity to develop somatic mutations and with an enrichment for immune response-related gene sets. However, this has not been examined in Asian tumour samples, where population differences in genetic and dietary factors may have an impact on the immune system. Methods In this study, we determined the prevalence of germline APOBEC3B deletion and its association with breast cancer risk in a cross-sectional hospital-based Asian multi-ethnic cohort of 1451 cases and 1442 controls from Malaysia. We compared gene expression profiles of breast cancers arising from APOBEC3B deletion carriers and non-carriers using microarray analyses. Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT. Results The minor allelic frequency of APOBEC3B deletion was estimated to be 0.35, 0.42 and 0.16 in female populations of Chinese, Malay and Indian descent, respectively, and that germline APOBEC3B deletion was associated with breast cancer risk with odds ratios of 1.23 (95 % CI: [1.05, 1.44]) for one-copy deletion and 1.38 (95 % CI: [1.10, 1.74]) for two-copy deletion compared to women with no deletion. Germline APOBEC3B deletion was not associated with any clinicopathologic features or the expression of any APOBEC family members but was associated with immune response-related gene sets (FDR q values