Song Yao

Background: It is unknown whether lower obesity in Asian American women contributes to their better survival after breast cancer diagnosis compared with non-Latina White women. Methods: In the Asian American Resiliency and Cancer cohort, with 3919 Asian American and 4978 non-Latina White women with breast cancer, we examined associations between all-cause and breast cancer–specific mortality, body mass index (BMI), and in a subset, waist circumference, waist-to-hip ratio, and waist-to-height ratio. Using multivariable-adjusted Cox proportional hazards regression, we estimated hazards ratios (HRs) and 95% confidence intervals, stratified by race and ethnicity, Asian ethnicity, menopausal status, and hormone receptor status. Results: With 2594 overall deaths and 1120 breast cancer deaths, all-cause mortality risk increased with higher BMI (per 5 kg/m2) in Asian American (HR = 1.13, 95% CI = 1.05 to 1.21) and non-Latina White (HR = 1.09, 95% CI = 1.04 to 1.14) women. In the subset with abdominal adiposity measures (1427 overall and 641 breast cancer deaths), the range of hazard ratios per unit increase was similar for Asian American (range = 1.18 to 1.34) and non-Latina White (range = 1.14 to 1.19) women. For overall and abdominal obesity, with a few exceptions, associations were observed primarily for postmenopausal women with hormone receptor–positive breast cancer, although heterogeneity was not statistically significant. The survival difference between Asian American and non-Latina White women remained after adjustment for BMI (HR = 0.88, 95% CI = 0.78 to 0.997). Obesity measures were not associated with breast cancer–specific mortality, except for waist-to-hip ratio and waist-to-height ratio in Chinese women. Conclusions: Our findings suggest that differences in overall and abdominal obesity do not explain the breast cancer survival differences between the two populations.

Background: Antibody–drug conjugates have substantially improved outcomes for patients with HER2-positive (HER2+) metastatic breast cancer. Whether these survival gains have translated equitably across racial and ethnic groups remains unclear despite persistent disparities in breast cancer outcomes. Methods: We conducted a retrospective cohort study using de-identified electronic health record data from the TriNetX Research Network (2010-2024). Adults with HER2+ metastatic breast cancer treated with trastuzumab deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1) were included. Overall survival was estimated using Kaplan–Meier methods and compared across racial and ethnic groups. Multivariable Cox models adjusted for age, body mass index, chronic obstructive pulmonary disease, hypertension, diabetes mellitus, and prior lines of therapy. Results: The cohort included 7462 patients with HER2+ metastatic breast cancer: 5072 non-Hispanic White (68%), 1193 Black (16%), 746 Hispanic (10%), and 298 Asian (4%). Five-year overall survival was highest among Asian (89.9%) and Hispanic (86.3%) patients, followed by non-Hispanic White (84.0%) and Black patients (80.3%) (P < .001). Compared with non-Hispanic White patients, Black patients experienced worse overall survival (adjusted hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 1.03 to 1.45; P = .03). Survival differences among Asian and Hispanic patients were not observed after multivariable adjustment. Conclusions: Among patients with HER2+ metastatic breast cancer treated with HER2-directed antibody–drug conjugates, Black patients experienced persistently inferior survival despite receipt of effective therapies. These findings highlight ongoing inequities and underscore the need for interventions to ensure equitable translation of therapeutic advances across all populations.

Genome-wide association studies (GWAS) have identified over 200 genetic risk loci for breast cancer, yet their target genes remain largely unknown. We conduct multi-ancestry transcriptome-wide association studies (TWAS) to discover potential breast cancer susceptibility genes. We develop ancestry-specific genetic models to predict levels of gene expression, alternative splicing, and 3' UTR alternative polyadenylation using genomic and transcriptomic data from 652 normal female tissue samples and apply these models to GWAS data of 178,534 cases and 248,300 controls for association analyses. We identify 290 genes associated with breast cancer risk, including 103 previously unreported and 46 not located at known GWAS loci, and 39 genes show distinct associations with breast cancer risk by estrogen-receptor status. Single-cell RNA sequencing and in vitro experiment data provide additional functional evidence for 169 genes. These genes are enriched in pathways implicated in breast carcinogenesis. Our study uncovers insights into breast cancer genetics and biology.

Racial and ethnic disparities exist in cardiovascular disease (CVD) burden in the general population; yet surprisingly few studies have examined such disparities in breast cancer patients, who are at higher risk due to cardiotoxic therapy. To investigate incidence of CVD and cardiometabolic risk factors across Asian, non-Hispanic Black (NHB), Hispanic, and non-Hispanic White (NHW) women with a history of breast cancer. In 4,071 women with breast cancer from a prospective cohort, the incidence of cardiometabolic risk factors and CVD occurring after breast cancer diagnosis were analyzed with self-identified race and ethnicity (SIRE) and global genetic ancestry. Racial and ethnic differences existed in the prevalence of cardiometabolic risk factors and CVD before breast cancer diagnosis, which continued to manifest in incident cases after cancer treatment. Asian, NHB, and Hispanic women were all at higher risk of diabetes than NHW women. Nonetheless, only NHB women had higher risk of CVD events, and Hispanic women were at lower risk. The apparent lower risk of CVD in Asian women largely disappeared after adjustment for covariates. Similar differences across SIRE groups were found in the cardiotoxic chemotherapy subgroup and the subgroup without chemotherapy, except for any CVD and VTE showing modifying effects of cardiotoxic chemotherapy. Analyses of genetic ancestry revealed similar results to SIRE. Our study reveals racial and ethnic disparities in cardiometabolic risk factors and CVD events before and after breast cancer diagnosis. Clinical and research attention is warranted to bridge the population-level gaps in CVD morbidity and mortality. Statement of Significance: Our study provides strong evidence for racial and ethnic disparities in cardiovascular disease before and after breast cancer diagnosis. Clinical and research attention is warranted to bridge these population-level gaps.

In the US, Asian American females with breast cancer have better survival than other groups, and survival differs across Asian American ethnicities. Reasons remain unclear. We compared the survival of 5294 Asian American ethnicities and 5294 non-Latina White (NLW) females with incident stage I-IV breast cancer (2000-2015) in Kaiser Permanente Northern California. With follow-up through December 31, 2020, survival analysis was conducted using cause-specific Cox proportional hazards models adjusting for sociodemographic, clinical, treatment, social environment, and lifestyle factors. Overall, 1048 deaths (581 breast cancer-related) occurred in Asian American females and 1673 deaths (779 breast cancer-related) in NLW females. Compared with NLW females, Asian American females were younger (median = 56.2 vs. 63.0 years), lived in the highest socioeconomic status neighborhoods (Quintiles 4/5 = 57.7% vs. 50.3%), had fewer comorbidities (45.2% vs. 35.9% with zero), had a lower body mass index (BMI) (median = 24.8 vs. 27.4 kg/m²), and never smoked (47.2% vs. 26.9%), varying by Asian American ethnicity. All-cause mortality was lower in Asian American than NLW females (hazard ratio [HR] = 0.82; 95% CI = 0.74 to 0.91). Chinese (HR = 0.84; 95% CI = 0.70 to 1.00), Japanese (HR = 0.69; 95% CI = 0.55 to 0.88), and South Asian (HR = 0.73; 95% CI = 0.53 to 0.99) females had persistent survival advantages over NLW females. Adjusting for BMI and smoking attenuated associations. For breast cancer-specific mortality, associations were similar, though statistically non-significant. Asian American females—especially those of Chinese, Japanese, and South Asian descent—had better survival than non-Latina NLW females. Disaggregating Asian American ethnicities clarifies survival differences and may inform research on personal, social, and lifestyle factors to benefit all patients.

Polygenic risk score (PRS) models effectively predict breast cancer (BC) risk in European-ancestry women but have limited accuracy for African-ancestry women, particularly for aggressive subtypes. We developed PRS models for overall BC, estrogen receptor (ER)-positive, ER-negative and triple-negative BC (TNBC) in African-ancestry women using data from the African Ancestry Breast Cancer Genetics consortium (17,391 cases and 18,800 controls). We applied several PRS methods and integrated information across ancestries and BC subtypes. The best models for overall, ER-positive, ER-negative and TNBC showed an area under the receiving operating curve of 0.612, 0.621, 0.611 and 0.639, respectively, and maintained predictive accuracy in external validation studies with area under the receiving operating curves of 0.612, 0.640, 0.605 and 0.652. We further introduce a parsimonious 162-variant PRS for TNBC with comparable accuracy (0.626). These findings demonstrate markedly improved PRS accuracy for BC risk prediction in African-ancestry women. Using these PRS models for screening will help promote more equitable cancer prevention efforts.

A simplified causal diagram of the relationship between time-varying diet quality, physical activity and smoking on survival after breast cancer

Immediate cause of death among Pathways participants who died during the study period (n=734)