Multi-omics profiling of younger Asian breast cancers reveals distinctive molecular signatures.

Breast cancer (BC) in the Asia Pacific regions is enriched in younger patients and rapidly rising in incidence yet its molecular bases remain poorly characterized. Here we analyze the whole exomes and transcriptomes of 187 primary tumors from a Korean BC cohort (SMC) enriched in pre-menopausal patients and perform systematic comparison with a primarily Caucasian and post-menopausal BC cohort (TCGA). SMC harbors higher proportions of HER2+ and Luminal B subtypes, lower proportion of Luminal A with decreased ESR1 expression compared to TCGA. We also observe increased mutation prevalence affecting BRCA1, BRCA2, and TP53 in SMC with an enrichment of a mutation signature linked to homologous recombination repair deficiency in TNBC. Finally, virtual microdissection and multivariate analyses reveal that Korean BC status is independently associated with increased TIL and decreased TGF-ß signaling expression signatures, suggesting that younger Asian BCs harbor more immune-active microenvironment than western BCs.

microRNA Expression in Ethnic Specific Early Stage Breast Cancer: an Integration and Comparative Analysis.

Breast cancer (BC) has a higher incidence in young Lebanese woman as compared to the West. We assessed the microRNA (miRNA) microarray profile of tissues derived from Lebanese patients with early BC and performed mRNA-miRNA integration analysis. 173 miRNAs were significantly dysregulated in 45 BC versus 17 normal adjacent breast tissues, including 74 with a fold change more than two of which 17 were never reported before in cancer. Integration analysis of mRNA-miRNA microarray data revealed a potential role of 51 dysregulated miRNA regulating 719 tumor suppressive or oncogenic mRNA associated with increased proliferation and decreased migration and invasion. We then performed a comparative miRNA microarray profile analysis of BC tissue between these 45 Lebanese and 197 matched American BC patients. Notably, Lebanese BC patients had 21 exclusively dysregulated miRNA (e.g. miR-31, 362-3p, and 663) and 4 miRNA with different expression manner compared to American patients (e.g. miR-1288-star and 324-3p). Some of these differences could reflect variation in patient age at diagnosis or ethnic variation affecting miRNA epigenetic regulation or sequence of miRNA precursors. Our data provide a basis for genetic/epigenetic investigations to explore the role of miRNA in early stage BC in young women, including ethnic specific differences.

Treatment of ductal carcinoma in situ among patients cared for in large integrated health plans.

OBJECTIVE: To examine whether use of adjuvant therapy varies by race/ethnicity among patients with ductal carcinoma in situ (DCIS) at 3 integrated health plan delivery sites based in California and Massachusetts. STUDY DESIGN: Cross-sectional study nested within a cohort of women diagnosed as having DCIS between 1990 and 2001. METHODS: We reviewed medical records of 3000 non-Hispanic white (69%), black (10%), Hispanic (9%), and Asian or Pacific Islander (12%) women diagnosed as having DCIS between 1990 and 2001 and treated with breast-conserving therapy. chi(2) Test and multinomial logistic regression analysis were used to examine the association between race/ethnicity and use of adjuvant treatments after controlling for patient and clinical variables, including certain pathologic factors. RESULTS: We found no significant differences in DCIS adjuvant treatment among racial/ethnic groups in bivariate or multinomial analyses after adjusting for demographic characteristics, comorbidity, and clinical factors. Minority women were as likely to undergo adjuvant radiation therapy as non-Hispanic white women. However, women 70 years or older (odds ratio, 0.40; 95% confidence interval, 0.31-0.51) and women who lived in areas with low geocoded median family income (odds ratio, 0.65; 95% confidence interval, 0.48-0.89) were less likely to receive adjuvant radiation therapy. Tumor size and comedo histologic growth pattern were associated with increased likelihood of receiving radiation therapy. CONCLUSION: Use of adjuvant therapy by minority women in these managed care plans is similar to that by non-Hispanic white women, although use was less among older women and among women who lived in poorer neighborhoods.

Reproductive history in relation to breast cancer risk among Hispanic and non-Hispanic white women.

OBJECTIVE: To evaluate reproductive history risk factors in breast cancer among Hispanic (HISP) women in the U.S. southwest, a population with approximately 33% lower breast cancer incidence than non-Hispanic whites (NHW). METHODS: Population-based case-control study of HISP (796 cases, 919 controls) and NHW (1,525 cases, 1,596 controls) women. RESULTS: 19.3% of HISP women reported five or more births and had a reduced risk of breast cancer, adjusted odds ratio (OR) 0.70 (95% confidence interval (CI): 0.50, 0.98) compared to those with one or two births. Breast cancer risk for HISP increased with older age at first birth, p trend = 0.008. Parity and age at first birth associations were specific to ER positive tumors. HISP women who had given birth within five years had higher breast cancer risk than women with 16-25 years since a birth, OR 2.62 (95% CI: 1.44, 4.78); the trend with years since last birth was stronger than for NHWs, p interaction = 0.05. CONCLUSIONS: Reproductive history influences on breast cancer risk among HISP were similar to associations reported for NHWs. Differences in the prevalence of reproductive risk factors would explain an estimated 6.6% lower breast cancer incidence for HISP compared to NHWs.