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Purpose: Several recurring pathogenic variants (PVs) in BRCA1/BRCA2 and additional cancer susceptibility genes are described in the ethnically diverse Israeli population. Since 2019, testing for these recurring PVs is reimbursed unselectively for all patients with breast cancer (BC) in Israel. The aim was to evaluate the yield of genotyping for these PVs in non-Ashkenazi Jewish (AJ) patients with BC diagnosed ≥age 50 years., Methods: Clinical and genotyping data of all patients with BC undergoing oncogenetic counseling at the Oncology Institute at Sheba Medical Center from June 2017 to December 2023 were reviewed., Results: Of 2706 patients with BC (mean age at diagnosis, 54 years; range, 20-92 years) counseled, 515 patients of non-AJ (all four grandparents) descent, diagnosed ≥age 50 years of age were genotyped, 55 with triple-negative BC (TNBC) and 460 with non-TNBC. One of the recurring PVs in BRCA1/BRCA2 were detected in 12.7% (7/55) of TNBC patients and 0.65% (3/460) of non-TNBC. One patient with non-TNBC had PMS2 PV. Low-penetrance variants were found in 2.5% of genotyped TNBC and in 3.7% of patients with non-TNBC, including CHEK2 c.499G>A (n = 3), APC c.3920T > A (n = 4), and heterozygous MUTYH c.1187G>A (n = 5). Following first-pass genotyping, 146 patients performed multigene panel testing, none carried a BRCA1/BRCA2 PV, and only 5/127 non-TNBC (3.9%) harbored PVs in CHEK2 (n = 2, c.846+1G>C and c.592+3A>T), ATM c.103C>T (n = 2), and NBN c.966C>G (n = 1)., Conclusions: The observed low rates of PV detection in non-AJ non-TNBC cases ≥age 50 years at diagnosis, mostly for clinically insignificant variants, questions the justification of unselected genotyping in this subset of patients., (© 2024 American Cancer Society.)

Purpose: Breast cancer mortality is higher in Black women than other racial groups. This difference has been partially attributed to a higher proportion of triple-negative breast cancer (TNBC). However, it is uncertain if survival disparities exist in racially diverse TNBC patients receiving similar treatments. Here, we examine racial differences in disease-related outcomes in TNBC patients treated on the E5103 clinical trial., Methods: From 2007 to 2011, 4,994 patients with stage I-III HER2-negative breast cancer were randomized to adjuvant chemotherapy with or without bevacizumab. This analysis was limited to the subset of 1,742 TNBC patients with known self-reported race. Unadjusted Kaplan-Meier curves and adjusted Cox-Proportional Hazards models were used to determine breast cancer events and survival outcomes., Results: Of the analysis population, 51 (2.9%) were Asian, 269 (15.4%) Black, and 1422 (81.6%) White. Median age was 51 years. Patient characteristics, treatment arm, and local therapies were similar across racial groups. White women were more commonly node-negative (56% vs. 49% and 44% in Asian and Black women, respectively; p < 0.01). At a median follow-up of 46 months, unadjusted Kaplan-Meier locoregional and distant recurrence, and disease-free and overall survival, did not differ significantly by race. In Cox models adjusted for patient and tumor characteristics and treatment arm, race was not associated with any disease event. Larger tumor size and nodal involvement were consistently associated with breast cancer events., Conclusion: This clinical trial population of similarly treated TNBC patients showed no racial differences in breast cancer outcomes. Disease extent, rather than race, was associated with disease events., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

African American (AA) women are twice as likely to develop triple-negative breast cancer (TNBC) as women of European descent. Additionally, AA women with TNBC present a much more aggressive disease course than their European American (EA) counterparts. Thus, there is an unmet clinical need to identify race-specific biomarkers and improve survival outcomes in AA patients with TNBC. The minus-end directed microtubule motor protein kinesin family member C1 (KIFC1) promotes centrosome clustering and chromosomal instability and is often overexpressed in TNBC. Previous findings suggest that KIFC1 plays a role in cell proliferation and migration in TNBC cells from AAs and that the levels of nuclear KIFC1 (nKIFC1) are particularly high in AA patients with TNBC. The nuclear localization of KIFC1 in interphase may underlie its previously unrecognized race-specific association. In this study, we found that in TNBC cells derived from AAs, nKIFC1 interacted with the tumor suppressor myosin heavy chain 9 (MYH9) over EA cells. Treatment of AA TNBC cells with commercial inhibitors of KIFC1 and MYH9 disrupted the interaction between KIFC1 and MYH9. To characterize the racial differences in the KIFC1-MYH9-MYC axis in TNBC, we established homozygous KIFC1 knockout (KO) TNBC cell lines. KIFC1 KO significantly inhibited proliferation, migration, and invasion in AA TNBC cells but not in EA TNBC cells. RNA sequencing analysis showed significant downregulation of genes involved in cell migration, invasion, and metastasis upon KIFC1 KO in TNBC cell lines from AAs compared to those from EAs. These data indicate that mechanistically, the role of nKIFC1 in driving TNBC progression and metastasis is stronger in AA patients than in EA patients, and that KIFC1 may be a critical therapeutic target for AA patients with TNBC., (© 2024. The Author(s).)

Purpose: Recruit and sequence breast cancer subjects in Guatemalan and US Hispanic populations. Identify optimum strategies to recruit Latin American and Hispanic women into genetic studies of breast cancer., Methods: We used targeted gene sequencing to identify pathogenic variants in 19 familial breast cancer susceptibility genes in DNA from unselected Hispanic breast cancer cases in the US and Guatemala. Recruitment across the US was achieved through community-based strategies. In addition, we obtained patients receiving cancer treatment at major hospitals in Texas and Guatemala., Results: We recruited 287 Hispanic US women, 38 (13%) from community-based and 249 (87%) from hospital-based strategies. In addition, we ascertained 801 Guatemalan women using hospital-based recruitment. In our experience, a hospital-based approach was more efficient than community-based recruitment. In this study, we sequenced 103 US and 137 Guatemalan women and found 11 and 10 pathogenic variants, respectively. The most frequently mutated genes were BRCA1, BRCA2, CHEK2, and ATM. In addition, an analysis of 287 US Hispanic patients with pathology reports showed a significantly higher percentage of triple-negative disease in patients with pathogenic variants (41% vs. 15%). Finally, an analysis of mammography usage in 801 Guatemalan patients found reduced screening in women with a lower socioeconomic status (p < 0.001)., Conclusion: Guatemalan and US Hispanic women have rates of hereditary breast cancer pathogenic variants similar to other populations and are more likely to have early age at diagnosis, a family history, and a more aggressive disease. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients to reduce breast cancer mortality in Hispanic women., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Racial disparities in breast cancer outcomes are well described across the spectrum of screening, diagnosis, treatment, and survivorship. Breast cancer mortality is markedly elevated for Non-Hispanic Black women compared with other racial and ethnic groups, with multifactorial causes. Here, we aim to reduce this burden by identifying disparities in breast cancer risk factors, risk assessment, and risk management before breast cancer is diagnosed. We describe a reproductive profile and modifiable risk factors specific to the development of triple-negative breast cancer. We also propose that screening strategies should be both risk- and race-based, given the prevalence of early-onset triple-negative breast cancer in young Black women. We emphasize the importance of early risk assessment and identification of patients at hereditary and familial risk and discuss indications for a high-risk referral. We discuss the subtleties following genetic testing and highlight "uncertain" genetic testing results and risk estimation challenges in women who test negative. We trace aspects of the obesity epidemic in the Black community to infant feeding patterns and emphasize healthy eating and activity. Finally, we discuss building an environment of trust to foster adherence to recommendations, follow-up care, and participation in clinical trials. Addressing relevant social determinants of health; educating patients and clinicians on factors impacting disparities in outcomes; and encouraging participation in targeted, culturally sensitive research are essential to best serve all communities., Competing Interests: Declaration of competing interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Black women have higher rates of death from triple-negative breast cancer (TNBC) than White women. We hypothesized that pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and overall survival (OS) may vary by race/ethnicity in patients with TNBC., Methods: We identified women 18 years and older with stage I-III TNBC who received NAC followed by surgery from the National Cancer Database (2010-2019). We excluded patients without race/ethnicity or pathology data. Primary outcomes were pCR rates and OS on the basis of race/ethnicity., Results: Forty thousand eight hundred ninety women with TNBC met inclusion criteria (median age [IQR], 53 [44-61] years): 26,150 Non-Hispanic White (64%, NHW), 9,672 Non-Hispanic Black (23.7%, NHB), 3,267 Hispanic (8%), 1,368 Non-Hispanic Asian (3.3%, NHA), and 433 Non-Hispanic Other (1.1%, NHO) patients. Overall, 29.8% demonstrated pCR (NHW: 30.5%, NHB: 27%, Hispanic: 32.6%, NHA: 28.8%, NHO: 29.8%). Unadjusted OS was significantly higher for those with pCR compared with those with residual disease (5-year OS, 0.917 [95% CI, 0.911 to 0.923] v 0.667 [95% CI, 0.661 to 0.673], log-rank P < .001), and this association persisted after adjustment for demographic and tumor factors. The effect of achieving pCR on OS did not differ by race/ethnicity (interaction P = .10). However, NHB patients were less likely (odds ratio [OR], 0.89 [95% CI, 0.83 to 0.95], P = .001) and Hispanic patients were more likely (OR, 1.19 [95% CI, 1.08 to 1.31], P = .001) to achieve pCR than NHW patients. After adjustment for patient and disease factors, including achievement of pCR, Hispanic (hazard ratio [HR], 0.76 [95% CI, 0.69 to 0.85], P < .001) and NHA (HR, 0.64 [95% CI, 0.55 to 0.75], P < .001) race/ethnicity remained associated with OS., Conclusion: Odds of achieving pCR and OS in patients with TNBC appear to be associated with race/ethnicity. Additional research is necessary to understand how race/ethnicity is associated with rates of pCR and OS, whether related to socioeconomic factors or biologic variables, or both.

Background: Latin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk., Methods and Study Population: We used the informativeness for assignment measure to select robust instrumental variables for the individual proportion of Native American ancestry. We then conducted separate Mendelian randomization (MR) analyses based on 1401 Colombian women, most of them from the central Andean regions of Cundinamarca and Huila, and 1366 Mexican women from Mexico City, Monterrey and Veracruz, supplemented by sensitivity and stratified analyses., Results: The proportion of Colombian Native American ancestry showed a putatively causal protective effect on BC risk (inverse variance-weighted odds ratio [OR] = 0.974 per 1% increase in ancestry proportion, 95% confidence interval [CI] 0.970-0.978, p = 3.1 × 10 -40 ). The corresponding OR for Mexican Native American ancestry was 0.988 (95% CI 0.987-0.990, p = 1.4 × 10 -44 ). Stratified analyses revealed a stronger association between Native American ancestry and familial BC (Colombian women: OR = 0.958, 95% CI 0.952-0.964; Mexican women: OR = 0.973, 95% CI 0.969-0.978), and stronger protective effects on oestrogen receptor (ER)-positive BC than on ER-negative and triple-negative BC., Conclusions: The present results point to an unconfounded protective effect of Native American ancestry on BC risk in both Colombian and Mexican women which appears to be stronger for familial and ER-positive BC. These findings provide a rationale for personalised prevention programmes that take genetic ancestry into account, as well as for future admixture mapping studies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Endocrine-resistant HR+/HER2- breast cancer (BC) and triple-negative BC (TNBC) are of interest for molecularly informed treatment due to their aggressive natures and limited treatment profiles. Patients of African Ancestry (AA) experience higher rates of TNBC and mortality than European Ancestry (EA) patients, despite lower overall BC incidence. Here, we compare the molecular landscapes of AA and EA patients with HR+/HER2- BC and TNBC in a real-world cohort to promote equity in precision oncology by illuminating the heterogeneity of potentially druggable genomic and transcriptomic pathways., Methods: De-identified records from patients with TNBC or HR+/HER2- BC in the Tempus Database were randomly selected (N = 5000), with most having stage IV disease. Mutations, gene expression, and transcriptional signatures were evaluated from next-generation sequencing data. Genetic ancestry was estimated from DNA-seq. Differences in mutational prevalence, gene expression, and transcriptional signatures between AA and EA were compared. EA patients were used as the reference population for log fold-changes (logFC) in expression., Results: After applying inclusion criteria, 3433 samples were evaluated (n = 623 AA and n = 2810 EA). Observed patterns of dysregulated pathways demonstrated significant heterogeneity among the two groups. Notably, PIK3CA mutations were significantly lower in AA HR+/HER2- tumors (AA = 34% vs. EA = 42%, P < 0.05) and the overall cohort (AA = 28% vs. EA = 37%, P = 2.08e-05). Conversely, KMT2C mutation was significantly more frequent in AA than EA TNBC (23% vs. 12%, P < 0.05) and HR+/HER2- (24% vs. 15%, P = 3e-03) tumors. Across all subtypes and stages, over 8000 genes were differentially expressed between the two ancestral groups including RPL10 (logFC = 2.26, P = 1.70e-162), HSPA1A (logFC = - 2.73, P = 2.43e-49), ATRX (logFC = - 1.93, P = 5.89e-83), and NUTM2F (logFC = 2.28, P = 3.22e-196). Ten differentially expressed gene sets were identified among stage IV HR+/HER2- tumors, of which four were considered relevant to BC treatment and were significantly enriched in EA: ERBB2&#95;UP.V1&#95;UP (P = 3.95e-06), LTE2&#95;UP.V1&#95;UP (P = 2.90e-05), HALLMARK&#95;FATTY&#95;ACID&#95;METABOLISM (P = 0.0073), and HALLMARK&#95;ANDROGEN&#95;RESPONSE (P = 0.0074)., Conclusions: We observed significant differences in mutational spectra, gene expression, and relevant transcriptional signatures between patients with genetically determined African and European ancestries, particularly within the HR+/HER2- BC and TNBC subtypes. These findings could guide future development of treatment strategies by providing opportunities for biomarker-informed research and, ultimately, clinical decisions for precision oncology care in diverse populations., (© 2023. The Author(s).)

Importance: There are few data on state variation in racial and ethnic disparities in incidence of triple-negative breast cancer (TNBC) in the US, limiting the ability to inform state-level health policy developments toward breast cancer equity., Objective: To quantify between and within racial and ethnic disparities in TNBC incidence rates (IRs) among US women across states., Design, Setting, and Participants: This cohort study using population-based cancer registry data included data for all women with TNBC diagnosed from January 1, 2015, to December 31, 2019, identified in the US Cancer Statistics Public Use Research Database. Data were analyzed from July through November 2022., Exposures: State and race and ethnicity (Hispanic, non-Hispanic American Indian or Alaska Native, non-Hispanic Asian or Pacific Islander, non-Hispanic Black, or non-Hispanic White) abstracted from medical records., Main Outcomes and Measures: The main outcomes were diagnosis of TNBC, age-standardized IR per 100 000 women, state-specific incidence rate ratios (IRRs) using the rate among White women in each state as a reference for between-population disparities, and state-specific IRRs using the race and ethnicity-specific national rate as a reference for within-population disparities., Results: The study included data for 133 579 women; 768 (0.6%) were American Indian or Alaska Native; 4969 (3.7%), Asian or Pacific Islander; 28 710 (21.5%), Black; 12 937 (9.7%), Hispanic; and 86 195 (64.5%), White. The TNBC IR was highest among Black women (25.2 per 100 000 women), followed by White (12.9 per 100 000 women), American Indian or Alaska Native (11.2 per 100 000 women), Hispanic (11.1 per 100 000 women), and Asian or Pacific Islander (9.0 per 100 000 women) women. Racial and ethnic group-specific and state-specific rates substantially varied, ranging from less than 7 per 100 000 women among Asian or Pacific Islander women in Oregon and Pennsylvania to greater than 29 per 100 000 women among Black women in Delaware, Missouri, Louisiana, and Mississippi. Compared with White women, IRRs were statistically significantly higher in 38 of 38 states among Black women, ranging from 1.38 (95% CI, 1.10-1.70; IR, 17.4 per 100 000 women) in Colorado to 2.32 (95% CI, 1.90-2.81; IR, 32.0 per 100 000 women) in Delaware; lower in 22 of 22 states among Asian or Pacific Islander women, varying from 0.50 (95% CI, 0.34-0.70; IR, 5.7 per 100 000 women) in Oregon to 0.82 (95% CI, 0.75-0.90; IR, 10.5 per 100 000 women) in New York; and did not differ among Hispanic and American Indian or Alaska Native women in 22 of 35 states and 5 of 8 states, respectively. State variations within each racial and ethnic population were smaller but still substantial. For example, among White women, compared with the national rate, IRRs varied from 0.72 (95% CI, 0.66-0.78; IR, 9.2 per 100 000 women) in Utah to 1.18 (95% CI, 1.11-1.25; IR, 15.2 per 100 000 women) in Iowa, 1.15 (95% CI, 1.07-1.24; IR, 14.8 per 100 000 women) in Mississippi, and 1.15 (95% CI, 1.07-1.24; IR, 14.8 per 100 000 women) in West Virginia., Conclusions and Relevance: In this cohort study, there were substantial state variations in racial and ethnic disparities in TNBC incidence, with Black women in Delaware, Missouri, Louisiana, and Mississippi having the highest rates among all states and racial and ethnic populations. The findings suggest that more research is needed to identify factors contributing to the substantial geographic variations in racial and ethnic disparities in TNBC incidence to develop effective preventive measures and that social determinants of health contribute to the geographic disparities in TNBC risk.

With the properties of aggressive cancer and heterogeneous tumor biology, triple-negative breast cancer (TNBC) is a type of breast cancer known for its poor clinical outcome. The lack of estrogen, progesterone, and human epidermal growth factor receptor in the tumors of TNBC leads to fewer treatment options in clinics. The incidence of TNBC is higher in African American (AA) women compared with European American (EA) women with worse clinical outcomes. The significant factors responsible for the racial disparity in TNBC are socioeconomic lifestyle and tumor biology. The current study considered the open-source gene expression data of triple-negative breast cancer samples' racial information. We implemented a state-of-the-art classification Support Vector Machine (SVM) method with a recurrent feature elimination approach to the gene expression data to identify significant biomarkers deregulated in AA women and EA women. We also included Spearman's rho and Ward's linkage method in our feature selection workflow. Our proposed method generates 24 features/genes that can classify the AA and EA samples 98% accurately. We also performed the Kaplan-Meier analysis and log-rank test on the 24 features/genes. We only discussed the correlation between deregulated expression and cancer progression with a poor survival rate of 2 genes, KLK10 and LRRC37A2 , out of 24 genes. We believe that further improvement of our method with a higher number of RNA-seq gene expression data will more accurately provide insight into racial disparity in TNBC.

Objective: To investigate the impact of global and local genetic ancestry and neighborhood socioeconomic status (nSES), on breast cancer (BC) subtype, and gene expression., Background: Higher rates of aggressive BC subtypes [triple negative breast cancer (TNBC)] and worse overall BC survival are seen in black women [Hispanic Black (HB) and non-Hispanic Black (NHB)] and women from low nSES. However, the complex relationship between genetic ancestry, nSES, and BC subtype etiology remains unknown., Methods: Genomic analysis was performed on the peripheral blood from a cohort of 308 stage I to IV non-Hispanic White (NHW), Hispanic White (HW), HB, and NHB women with BC. Patient and tumor characteristics were collected. Global and local ancestral estimates were calculated. Multinomial logistic regression was performed to determine associations between age, stage, genetic ancestry, and nSES on rates of TNBC compared to estrogen receptor (ER+)/epidermal growth factor receptor 2 (HER2-), ER+/HER2+, and ER-/HER2+ disease., Results: Among 308 women, we identified a significant association between increasing West African (WA) ancestry and odds of TNBC [odds ratio (OR): 1.06, 95% confidence interval (95% CI): 1.001-1.126, P =0.046] as well as an inverse relationship between higher nSES and TNBC (OR: 0.343, 95% CI: 0.151-0.781, P =0.011). WA ancestry remained significantly associated with TNBC when adjusting for patient age and tumor stage, but not when adjusting for nSES (OR: 1.049, 95% CI: -0.987-1.116, P =0.120). Local ancestry analysis, however, still revealed nSES-independent enriched WA ancestral segment centered at χ 2 =42004914 ( p =3.70×10 -5 ) in patients with TNBC., Conclusions: In this translational epidemiologic study of genetic ancestry and nSES on BC subtype, we discovered associations between increasing WA ancestry, low nSES, and higher rates of TNBC compared to other BC subtypes. Moreover, on admixture mapping, specific chromosomal segments were associated with WA ancestry and TNBC, independent of nSES. However, on multinomial logistic regression adjusting for WA ancestry, women from low nSES were more likely to have TNBC, independent of genetic ancestry. These findings highlight the complex nature of TNBC and the importance of studying potential gene-environment interactions as drivers of TNBC., Competing Interests: J.W.H. is an inventor of intellectual property related to gene expression profiling in uveal melanoma. He is a paid consultant for Castle Biosciences, licensee of this intellectual property, and he receives royalties from its commercialization. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Racial disparities in mortality due to metastasis remain significant among breast cancer patients. Chemokine receptors contribute to breast tumors and metastatic outcome. We explored for significant differences in chemokine receptor expression in breast tumors from Black, Asian, and White patients in The Cancer Genome Atlas. We show that despite sharing the same molecular subtype, expression of the chemokine receptors ACKR1, CCR3, CCR6, CCRL1, CCRL2, CXCR1, CXCR2, CXCR4, CXCR6, and CXC3CR1 was significantly different depending on racial group. For patients with triple negative breast cancer, CCR3 was higher in Black versus White and CCRL2 was higher in Asian versus White. In luminal A tumors, ACKR1 was lower in Asian versus White, CCR3 was higher in Black versus White, and CCR6 and CXC3CR1 were lower in Black versus White. In luminal B tumors, CCRL2 was lower in Black versus White, CXCR1 and CXC3CR1 were lower in Asian versus White, and CXCR2 was lower in Black and Asian versus White. In HER2 enriched tumors, CCR3 was higher in Black versus White and CXCR4 lower in Asian versus White. CCR3, CCR6, and CXCR6 associated with worse patient survival. These findings can inform improved treatment strategies to decrease racial disparities in breast cancer burden., (© 2022. The Author(s).)

Background: Triple-negative breast cancer (TNBC) represents about 19% of all breast cancer cases in the Chinese population. Lack of targeted therapy contributes to the poorer outcomes compared with other breast cancer subtypes. Comprehensive genomic profiling helps to explore the clinically relevant genomic alterations (CRGAs) and potential therapeutic targets in very-early-relapsed TNBC patients., Methods: Formalin-fixed paraffin-embedded (FFPE) tumour tissue specimens from 23 patients with very-early-relapsed TNBC and 13 patients with disease-free survival (DFS) more than 36 months were tested by FoundationOne CDx (F1CDx) in 324 genes and select gene rearrangements, along with genomic signatures including microsatellite instability (MSI) and tumour mutational burden (TMB)., Results: In total, 137 CRGAs were detected in the 23 very-early-relapsed TNBC patients, averaging six alterations per sample. The mean TMB was 4 Muts/Mb, which was higher than that in non-recurrence patients, and is statistically significant. The top-ranked altered genes were TP53 (83%), PTEN (35%), RB1 (30%), PIK3CA (26%) and BRCA1 (22%). RB1 mutation carriers had shorter DFS. Notably, 100% of these patients had at least one CRGA, and 87% of patients had at least one actionable alteration. In pathway analysis, patients who carried a mutation in the cell cycle pathway were more likely to experience very early recurrence. Strikingly, we detected one patient with ERBB2 amplification and one patient with ERBB2 exon20 insertion, both of which were missed by immunohistochemistry (IHC). We also detected novel alterations of ROS1-EPHA7 fusion for the first time, which has not been reported in breast cancer before., Conclusions: The comprehensive genomic profiling can identify novel treatment targets and address the limited options in TNBC patients. Therefore, incorporating F1CDx into TNBC may shed light on novel therapeutic opportunities for these very-early-relapsed TNBC patients.

Triple negative breast cancers (TNBC) behave more aggressively than hormone-receptor positive breast cancers. They are also known preferentially to affect young black women, often leading to poorer outcomes compared with those for white women. We sought to evaluate the comprehensive patterns of failure associated with treatment for TNBC at an urban institution with a predominantly black population and to assess the impact of social determinants of health on treatment failure. A retrospective review of TNBC patients treated from 2005 to 2015 was conducted. Detailed patient, tumor, and treatment characteristics and information on patterns of failure were included. With a median follow-up of 46 months, 32 (16%) documented failures occurred. Locoregional failures comprised 84% of failure patterns whether isolated or in combination with distant failure. Treatment failure was associated with insurance type and smoking status, as well as several tumor characteristics. On multivariate analysis, pathologic nodal staging was the most significant predictor of treatment failure. In contrast to previous studies, we found that black women had higher overall survival than white women, but race was not associated with differences in recurrence patterns or with likelihood of treatment failure. Regardless of race, of the patients who recurred, 53% failed in distant and locoregional sites simultaneously, with an additional 34% failing locally only. These results highlight the need for aggressive local therapies in high-risk patients and suggest a need for improved follow-up focusing on detecting locoregional failures. Multidisciplinary care is essential in the management of these patients at time of failure., (© 2020. W. Montague Cobb-NMA Health Institute.)

In Ethiopia, a breast cancer diagnosis is associated with a prognosis significantly worse than that of Europe and the US. Further, patients presenting with breast cancer in Ethiopia are far younger, on average, and patients are typically diagnosed at very late stages, relative to breast cancer patients of European descent. Emerging data suggest that a large proportion of Ethiopian patients have hormone-positive (ER + ) breast cancer. This is surprising given (1) that patients have late-stage breast cancer at the time of diagnosis, (2) that African Americans with breast cancer frequently have triple negative breast cancer (TNBC), and (3) these patients typically receive chemotherapy, not hormone-targeting drugs. To further examine the similarity of Ethiopian breast tumors to those of African Americans or of those of European descent, we sequenced matched tumor and normal adjacent tissue from Ethiopian patients from a small pilot collection. We identified mutations in 615 genes across all three patients, unique to the tumor tissue. Across this analysis, we found far more mutations shared between Ethiopian patient tissue and that from white patients (103) than we did comparing to African Americans (3). Several mutations were found in extracellular matrix encoding genes with known roles in tumor cell growth and metastasis. We suggest future mechanistic studies on this disease focus on these genes first, toward finding new treatment strategies for breast cancer patients in Ethiopia., (© 2021. Biomedical Engineering Society.)

African American women are at increased risk of being diagnosed at a young age and/or with triple negative breast cancer, both factors which are included in current guidelines for identifying women who may benefit from genetic testing. Commercial breast cancer predisposition genetic panels, based largely on data derived from women of European ancestry, may not capture the full spectrum of cancer predisposition genes associated with breast cancer in African American women. Between 2001 and 2018, 488 unselected African American women with invasive breast cancer enrolled in the Clinical Breast Care Project. National Comprehensive Cancer Network (NCCN) Hereditary Cancer testing criteria version 1.2020 were applied to determine genetic risk. Targeted sequencing was performed using the TruSight Cancer panel and variants classified using the ClinVar database. Using NCCN criteria, 64.1% of African American women would be eligible for genetic testing. Fifty pathogenic or likely pathogenic mutations were detected in 19 genes with the highest frequencies in BRCA2 (29.4%) and BRCA1 (15.7%). Mutation frequencies in test-eligible and test-ineligible women were 13.1% and 3.5%, respectively. One-third of women harbored variants that could not be classified. While these data do not suggest a need to expand current commercial gene panels, NCCN criteria would fail to identify 12.5% of African American women with mutations in hereditary cancer predisposing genes.

Background: Non-Hispanic black women (NHB) are diagnosed with triple negative breast cancer (TNBC) more often than other ethnic or racial groups in the United States (US). This study describes regional differences in TNBC incidence among NHB women in the US from 2011 to 2015., Methods: We analyzed data from the United States Cancer Statistics (USCS) that includes incidence data from the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) programs., Results: Compared to the incidence rate for NHB women in the South, rates were significantly lower in the Northeast (22.6 per 100,000), higher in the Midwest (25.5 per 100,000) and similar in the West. These regional differences might be explained by genetic admixture among people with different geographic ancestral origins., Conclusions: Results from this study highlight the need to extend etiological research and evidence-based cancer prevention and control efforts to women at high risk of this disease in order to decrease cancer disparities., (Published by Elsevier Inc.)

It is unclear whether racial/ethnic disparities in triple-negative breast cancer (TNBC) mortality remain after accounting for clinical characteristics, treatment, and access-to-care-related factors. In this study, women with a primary diagnosis of TNBC during 2010-2014 were identified from the National Cancer Database. Hazard ratios (HR) and 95% confidence intervals (CI) for 3- and 5-year all-cause mortality associated with race/ethnicity were estimated using Cox proportional hazards models with stepwise adjustments for age, clinical characteristics, treatment, and access-to-care-related factors. Of 78,708 patients, non-Hispanic (NH) black women had the lowest 3-year overall survival rates (79.4%), followed by NH-whites (83.1%), Hispanics (86.0%), and Asians (87.1%). After adjustment for clinical characteristics, NH-blacks had a 12% higher risk of dying 3 years post-diagnosis (HR, 1.12; 95% CI, 1.07-1.17), whereas Hispanics and Asians had a 24% (HR, 0.76; 95% CI, 0.70-0.83) and 17% (HR, 0.83; 95% CI, 0.73-0.94) lower risk than their NH-white counterparts. The black-white disparity became non-significant after combined adjustment for treatment and access-to-care-related factors (HR, 1.04; 95% CI, 0.99-1.09), whereas the white-Hispanic and white-Asian differences remained. Stratified analyses revealed that among women aged less than or equal to 50 with stage III cancer, the elevated risk among NH-blacks persisted (HR, 1.20; 95% CI, 1.04-1.39) after full adjustments. Similar results were seen for 5-year mortality. Overall, clinical characteristics, treatment, and access-to-care-related factors accounted for most of the white-black differences in all-cause mortality of TNBC but explained little about Hispanic- and Asian-white differences. SIGNIFICANCE: These findings highlight the need for equal healthcare to mitigate the black-white disparity and for investigations of contributors beyond healthcare for lower mortality among Asians and Hispanics., (©2020 American Association for Cancer Research.)

Background: Evidence suggests etiologic heterogeneity among breast cancer subtypes. Previous studies with six-marker IHC classification of intrinsic subtypes included small numbers of black women., Methods: Using centralized laboratory results for estrogen receptor (ER), progesterone receptor, HER2, proliferation marker, Ki-67, EGFR, and cytokeratin (CK)5/6, we estimated case-only and case-control ORs for established breast cancer risk factors among cases ( n = 2,354) and controls ( n = 2,932) in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. ORs were estimated by ER status and intrinsic subtype using adjusted logistic regression., Results: Case-only analyses by ER status showed etiologic heterogeneity by age at menarche, parity (vs. nulliparity), and age at first birth. In case-control analyses for intrinsic subtype, increased body mass index and waist-to-hip ratio (WHR) were associated with increased risk of luminal A subtype, whereas older age at menarche and parity, regardless of breastfeeding, were associated with reduced risk. For basal-like cancers, parity without breastfeeding and increasing WHR were associated with increased risk, whereas breastfeeding and age ≥25 years at first birth were associated with reduced risk among parous women. Basal-like and ER - /HER2 + subtypes had earlier age-at-incidence distribution relative to luminal subtypes., Conclusions: Breast cancer subtypes showed distinct etiologic profiles in the AMBER consortium, a study of more than 5,000 black women with centrally assessed tumor biospecimens., Impact: Among black women, high WHR and parity without breastfeeding are emerging as important intervention points to reduce the incidence of basal-like breast cancer., (©2020 American Association for Cancer Research.)

Triple-negative breast cancer (TNBC) represents 15%-20% of all breast cancer types. It is more common among African American (AA) and Hispanic-Latina (HL) women. The biology of TNBC in HL women has been poorly characterized, but some data suggest that the molecular drivers of breast cancer might differ. There are no clinical tools to aid medical oncologists with decisions regarding appropriate individualized therapy, and no way to predict long-term outcomes. The aim of this study was to characterize individual patient gene mutation profiles and to identify the relationship with clinical outcomes. We collected formalin-fixed paraffin-embedded tumors (FFPE) from women with TNBC. We analyzed the gene mutation profiles of the collected tumors and compared the results with individual patient's clinical histories and outcomes. Of 25 patients with TNBC, 24 (96%) identified as HL. Twenty-one (84%) had stage III-IV disease. The most commonly mutated genes were TP53, NOTCH1, NOTCH2, NOTCH3, AKT, MEP3K, PIK3CA, and EGFR. Compared with other international cancer databases, our study demonstrated statistically significant higher frequencies of these genes among HL women. Additionally, a worse clinical course was observed among patients whose tumors had mutations in NOTCH genes and PIK3CA. This study is the first to identify the most common genetic alterations among HL women with TNBC. Our data strongly support the notion that molecular drivers of breast cancer could differ in HL women compared with other ethnic backgrounds. Therefore, a deeper understanding of the biological mechanisms behind NOTCH gene and PIK3CA mutations may lead to a new treatment approach., Competing Interests: The authors have declared that no competing interests exist.

Studies have demonstrated that environmental, host genetic, and socioeconomic factors influence the breast cancer prevalence landscape with a far-reaching influence on racial disparity to subtypes of breast cancer. To understand whether breast tissue harbors race-specific microbiota, we performed 16S rRNA gene-based sequencing of retrospective tumor and matched normal tissue adjacent to tumor (NAT) samples collected from Black non-Hispanic (BNH) and White non-Hispanic (WNH) women. Analysis of Triple Negative Breast cancer (TNBC) and Triple Positive Breast Cancer (TPBC) tissues for microbiota composition revealed significant differences in relative abundance of specific taxa at both phylum and genus levels between WNH and BNH women cohorts. Our main findings are that microbial diversity as measured by Shannon index was significantly lower in BNH TNBC tumor tissue as compared to matched NAT zone. In contrast, the WNH cohort had an inverse pattern for the Shannon index, when TNBC tumor tissue was compared to the matched NAT. Unweighted Principle Coordinates Analysis (PCoA) revealed a distinct clustering of tumor and NAT microbiota in both BNH and WNH cohorts.

Background: Women of African ancestry (WAA) are disproportionately affected by triple-negative breast cancer (TNBC), which remains one of the most clinically challenging breast cancer (BCa) subtypes. This study investigated the prevalence of TNBC and epidemiological trends for BCa in Barbados, a Caribbean island with a high percentage of African ancestry., Methods: Pathology reports for all BCa cases between 2007 and 2016 were collected from the sole hospital in Barbados and reviewed. The clinicopathological data collected included age, tumor grade, lymph node status, and hormone receptor status as determined by immunohistochemistry. BCa data for non-Hispanic white (NHW) and non-Hispanic black (NHB) American populations were accessed from the Surveillance, Epidemiology, and End Results database., Results: There were 1997 BCa cases in Barbados between 2007 and 2016 for an estimated incidence rate of 135.1 per 100,000 women in Barbados (standardized to the US population, where the standardized incidence rates for NHBs and NHWs were 141.4 and 152.6 per 100,000, respectively). Age-specific incidence rates in Barbados for this period were consistently higher in younger age groups (15-59 years) in comparison with NHWs and NHBs. Between 2010 and 2016 in Barbados, a TNBC prevalence of 25% was observed, whereas TNBC prevalences of 21% and 10% were observed in NHBs and NHWs, respectively., Conclusions: The BCa incidence was higher in younger Barbadian women than NHWs and NHBs, and the TNBC prevalence was ~2.5 times higher than the prevalence in NHWs. This hints at a possible genetic predisposition and other socioeconomic factors that could explain the high TNBC prevalence and aggressive clinical course in WAA globally., (© 2020 American Cancer Society.)

Purpose: Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared to whites, an aggressive breast cancer subtype associated with poor prognosis. There are no routinely used targeted clinical therapies for TNBC; thus there is a clear need to identify prognostic markers and potential therapeutic targets., Methods: We evaluated expression of 27,016 genes in 155 treatment-naïve TN tumors from AA women in Detroit. Associations with survival were evaluated using Cox proportional hazards models adjusting for stage and age at diagnosis, and p-values were corrected using a false discovery rate. Our validation sample consisted of 494 TN tumors using four publically available data sets. Meta-analyses were performed using summary statistics from the four validation results., Results: In the Detroit AA cohort, CLCA2 [Hazard ratio (HR) = 1.56, 95% confidence interval (CI) 1.31-1.86, nominal p = 5.1x10-7, FDR p = 0.014], SPIC [HR = 1.47, 95%CI 1.26-1.73, nominal p = 1.8x10-6, FDR p = 0.022], and MIR4311 [HR = 1.57, 95% CI 1.31-1.92, nominal p = 2.5x10-5, FDR p = 0.022] expression were associated with overall survival. Further adjustment for treatment and breast cancer specific survival analysis did not substantially alter effect estimates. CLCA2 was also associated with increased risk of death in the validation cohorts [HR = 1.14, 95% CI 1.05-1.24, p = 0.038, p-heterogeneity = 0.88]., Conclusions: We identified CLCA2 as a potential prognostic marker for TNBC in AA women., Competing Interests: The authors have declared that no competing interests exist.

Triple negative breast cancer (TNBC) is more prevalent in African Americans (AAs), has a more aggressive clinical course including a higher mortality rate and an increased occurrence of metastases. This study was designed to determine if racial differences at the molecular level might explain the more aggressive phenotype in AAs. Mutation profiling, was performed on 51 AA and 77 CA tumor/ normal pairs. Transcript expression analysis was performed on 35AA and 37CA. Genes with high frequency mutation rates such as MUC4 and TP53 were common to both racial populations, however genes that were less frequently mutated differed between the races suggesting that those cause the more aggressive nature of TNBC in AA women. JAK-Stat and HER2 signaling were unique to the AA and PTEN and mTOR were unique to the CA profiles. Many pathways identified by the mutational profiles were predicted to be down-regulated by the transcript expression profiles., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Drug resistance is the leading cause of breast cancer-related mortality in women, and triple negative breast cancer (TNBC) is the most aggressive subtype, affecting African American women more aggressively compared to Caucasians women. Of all cancer-related deaths, 15 to 20% are associated with inflammation, where proinflammatory cytokines have been implicated in the tumorigenesis process. The current study investigated the effects of the polyphenolic compound butein (2',3,4,4'-tetrahydroxychalcone) on cell proliferation and survival, as well as its modulatory effect on the release of proinflammatory cytokines in MDA-MB-231 (Caucasian) and MDA-MB-468 (African American) TNBC cell. The results obtained showed that butein decreased cell viability in a time and dose-dependent manner, and after 72-h of treatment, the cell proliferation rate was reduced in both cell lines. In addition, butein was found to have higher potency in MDA-MB-468, exhibiting anti-proliferative effects in lower concentrations. Apoptosis assays demonstrated that butein (50 μM) increased apoptotic cells in MDA MB-468, showing 60% of the analyzed cells in the apoptotic phase, compared to 20% in MDA-MB-231 cells. Additionally, butein downregulated both protein and mRNA expression of the proinflammatory cytokine, CCL2, and IKBKE in TNFα-activated Caucasian cells, but not in African Americans. This study demonstrates butein potential in cancer cell suppression showing a higher cytotoxic, anti-proliferative, and apoptotic effects in African Americans, compared to Caucasians TNBC cells. It also reveals the butein inhibitory effect on CCL2 expression with a possible association with IKBKE downregulation in MDA-MB-231 cells only, indicating that Caucasians and African Americans TNBC cells respond differently to butein treatment. The obtained findings may provide an explanation regarding the poor therapeutic response in African American patients with advanced TNBC., Competing Interests: The authors have declared that no competing interests exist.

Background: Black women with breast cancer have lower survival rates and higher recurrence rates in comparison with white women. This study compared treatment and survival outcomes for black and white women at a highly specialized tertiary care cancer center., Methods: An institutional review board-approved, retrospective institutional database review was performed to identify all black women treated for invasive breast cancer between 2005 and 2010. Women with a prior history of breast cancer, stage IV cancer, or bilateral breast cancer were excluded. White women had similar exclusion criteria applied and were then matched to black women 1:1 by age and diagnosis year. Clinicopathologic and treatment variables were compared by race. Kaplan-Meier methodology was used to estimate overall survival (OS) and disease-free survival (DFS); a multivariable analysis was conducted with Cox regression models., Results: The study group consisted of 1332 women (666 black). The median tumor size was larger in black women (1.6 vs 1.3 cm; P < .001). Black women had more nodal disease (41.1% vs 32%; P < .001) and had tumors that were more frequently an estrogen receptor-negative (32.9% vs 15%; P < .001), progesterone receptor-negative (47.1% vs 30.2%; P < .001), or triple-negative (TN) subtype (24% vs 8.9%; P < .001) in comparison with white women. Black women also had inferior DFS and OS; race was not an independent prognostic indicator in the multivariable analysis., Conclusions: Black women had more advanced disease and adverse prognostic indicators at diagnosis, but race was not an independent predictor of outcome. Black women were significantly more likely to have TN breast cancer. Further research is necessary to understand the differences in tumor biology associated with race., (© 2019 American Cancer Society.)

Background: In the USA, the breast cancer mortality rate is 41% higher for African-American women than non-Hispanic White women. While numerous gene expression studies have classified biological features that vary by race and may contribute to poorer outcomes, few studies have experimentally tested these associations. CRYβB2 gene expression has drawn particular interest because of its association with overall survival and African-American ethnicity in multiple cancers. Several reports indicate that overexpression of the CRYβB2 pseudogene, CRYβB2P1, and not CRYβB2 is linked with race and poor outcome. It remains unclear whether either or both genes are linked to breast cancer outcomes. This study investigates CRYβB2 and CRYβB2P1 expression in human breast cancers and breast cancer cell line models, with the goal of elucidating the mechanistic contribution of CRYβB2 and CRYβB2P1 to racial disparities., Methods: Custom scripts for CRYβB2 or CRYβB2P1 were generated and used to identify reads that uniquely aligned to either gene. Gene expression according to race and tumor subtype were assessed using all available TCGA breast cancer RNA sequencing alignment samples (n = 1221). In addition, triple-negative breast cancer models engineered to have each gene overexpressed or knocked out were developed and evaluated by in vitro, biochemical, and in vivo assays to identify biological functions., Results: We provide evidence that CRYβB2P1 is expressed at higher levels in breast tumors compared to CRYβB2, but only CRYβB2P1 is significantly increased in African-American tumors relative to White American tumors. We show that independent of CRYβB2, CRYβB2P1 enhances tumorigenesis in vivo via promoting cell proliferation. Our data also reveal that CRYβB2P1 may function as a non-coding RNA to regulate CRYβB2 expression. A key observation is that the combined overexpression of both genes was found to suppress cell growth. CRYβB2 overexpression in triple-negative breast cancers increases invasive cellular behaviors, tumor growth, IL6 production, immune cell chemoattraction, and the expression of metastasis-associated genes. These data underscore that both CRYβB2 and CRYβB2P1 promote tumor growth, but their mechanisms for tumor promotion are likely distinct., Conclusions: Our findings provide novel data emphasizing the need to distinguish and study the biological effects of both CRYβB2 and CRYβB2P1 as both genes independently promote tumor progression. Our data demonstrate novel molecular mechanisms of two understudied, disparity-linked molecules.

Objective: To investigate subtype-specific risk of germline alleles associated with triple negative breast cancer (TNBC) in African ancestry populations., Background: Breast cancer (BC) mortality is higher in African American (AA) compared to White American (WA) women; this disparity is partly explained by 2-fold higher TNBC incidence., Methods: We used a surgically maintained biospecimen cohort of 2884 BC cases. Subsets of the total (760 AA; 962 WA; 910 West African/Ghanaian; 252 East African/Ethiopian) were analyzed for genotypes of candidate alleles. A subset of 417 healthy controls were also genotyped, to measure associations with overall BC risk and TNBC., Results: TNBC frequency was highest in Ghanaian and AA cases (49% and 44% respectively; P < 0.0001) and lowest in Ethiopian and WA cases (17% and 24% respectively; P < 0.0001). TNBC cases had higher West African ancestry than non-TNBC (P < 0.0001). Frequency of the Duffy-null allele (rs2814778; an African ancestral variant adopted under selective pressure as protection against malaria) was associated with TNBC-specific risk (P < 0.0001), quantified West African Ancestry (P < 0.0001) and was more common in AA, Ghanaians, and TNBC cases. Additionally, rs4849887 was significantly associated with overall BC risk, and both rs2363956 and rs13000023 were associated with TNBC-specific risk, although none as strongly as the Duffy-null variant., Conclusions: West African ancestry is strongly correlated with TNBC status, as well as germline variants related to BC risk. The Duffy-null allele was associated with TNBC risk in our cohort.

We assessed the quality of life (QoL) associated with patient's characteristics and different cancer treatments among Chinese breast cancer survivors in Taiwan. A cross-sectional survey was conducted in 2017 where 193 patients with hormone receptor-positive/human epidermal growth factor receptor-2-negative metastatic breast cancer were recruited. Three QoL questionnaires were administered: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), its breast cancer supplementary measure (QLQ-BR23) and EQ-5D-5L. Multiple linear regression was performed to assess the association between QoL and cancer treatments, with adjustment for patient's characteristics. The mean age of study participants was 55.52 years. Simple linear regression showed that cancer stage and receiving chemotherapy were significantly associated with QoL scores (p < 0.05). Significant adverse effects of chemotherapy on QoL were found among early-stage cancer women (i.e., I or II), including poor cognitive and sexual functioning, and a higher symptom burden (i.e., dyspnoea, constipation, systematic therapy side effects). Multiple linear regression also revealed that receiving chemotherapy was significantly associated with poor QoL (e.g., lower functional health and higher symptom burden measured by the QLQ-BR23), compared to none chemotherapy (p < 0.05). Receiving chemotherapy was associated with poor QoL, especially among early-stage breast cancer patients., (© 2019 John Wiley & Sons Ltd.)

Aims: Triple-negative breast cancer comprises different histological subtypes, including metaplastic breast cancer (MBC) and ductal carcinomas (IDCs). The purpose of this study was to compare triple-negative MBC (TN-MBC) with triple-negative IDC (TN-IDC) in terms of survival and predictive factors., Methods: With access to the Surveillance, Epidemiology and End Result (SEER) database, a total of 19 383 patients met the eligibility criteria. Clinicopathological characteristics were compared between groups using the χ 2 test. Univariate and multivariate analyses were applied to evaluate the disease-specific survival (DSS) and overall survival (OS). Subgroup analyses summarised the hazard ratios of TN-MBC versus TN-IDC using a forest plot., Results: A total of 586 patients with TN-MBC and 18 797 with TN-IDC were included in this study. Patients with TN-MBC were older and presented with larger tumour sizes, relatively rare lymph node positive disease, and had received more chemotherapy. Compared with TN-IDC, the TN-MBC group showed a significantly poorer prognosis before and after the 1:3 matched case-control analysis. Further subgroup analysis indicated that patients with TN-MBC were older, were from specific races, and those with distant metastasis and not receiving radiotherapy had worse prognosis than patients with TN-IDC in terms of DFS and OS., Conclusion: Our results showed that patients with TN-MBC had unique clinicopathological characteristics and poorer prognostic subtype compared with TN-IDC. This improves our understanding of the clinicopathological and prognostic features of this rare entity but also provides more convincing therapeutic guidelines for TN-MBC in patients with breast cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Young black women are at higher risk of triple-negative breast cancer (TNBC); however, a majority of the genetic studies on cancer predisposition were carried out in White populations. The underrepresentation of minority racial/ethnic populations in cancer genetic studies may have led to disproportionate gaps in our knowledge of cancer predisposition genes in these populations. We surveyed the protein-truncating mutations at the exome-wide scale and in known breast cancer predisposition genes among 170 patients of multiple racial/ethnic groups with early-onset (≤age 50) TNBC from two independent cohorts. Black patients, on average, had a higher number of truncating mutations than Whites at the exome-wide level, but fewer truncating mutations in the panel of known breast cancer genes. White TNBC patients showed a strong enrichment of truncating variants in known breast cancer genes, whereas no such enrichment was found among Black patients. Our findings indicate likely more breast cancer disposition genes yet to be discovered in minority racial/ethnic groups, and the current multigene panels may result in unequal benefits from cancer genetic testing., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors and absence of amplification of human epidermal growth factor receptor (HER2). This disease has no approved treatment with a poor prognosis particularly in African-American (AA) as compared to European-American (EA) patients. Gene ontology analysis showed specific gene pathways that are differentially regulated and gene signatures that are differentially expressed in AA as compared to EA. Such differences might underlie the basis for the aggressive nature and poor prognosis of TNBC in AA patients. In-depth studies of these pathways and differential genetic signature might give significant clues to improve our understanding of tumor biology associated with AA TNBC to advance the prognosis and survival rates. Along with gene ontology analysis, we suggest that post-translational modifications (PTM) could also play a crucial role in the dismal survival rate of AA TNBC patients. Further investigations are necessary to explore this terrain of PTMs to identify the racially disparate burden in TNBC.

Purpose: Population-based incidence rates of breast cancers that are negative for estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2/ neu (triple-negative breast cancer [TNBC]) are higher among African American (AA) compared with white American (WA) women, and TNBC prevalence is elevated among selected populations of African patients. The extent to which TNBC risk is related to East African versus West African ancestry, and whether these associations extend to expression of other biomarkers, is uncertain., Methods: We used immunohistochemistry to evaluate estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2/ neu, androgen receptor and aldehyde dehydrogenase 1 (ALDH1) expression among WA (n = 153), AA (n = 76), Ethiopian (Eth)/East African (n = 90), and Ghanaian (Gh)/West African (n = 286) patients with breast cancer through an institutional review board-approved international research program., Results: Mean age at diagnosis was 43, 49, 60, and 57 years for the Eth, Gh, AA, and WA patients, respectively. TNBC frequency was higher for AA and Gh patients (41% and 54%, respectively) compared with WA and Eth patients (23% and 15%, respectively; P < .001) Frequency of ALDH1 positivity was higher for AA and Gh patients (32% and 36%, respectively) compared with WA and Eth patients (23% and 17%, respectively; P = .007). Significant differences were observed for distribution of androgen receptor positivity: 71%, 55%, 42%, and 50% for the WA, AA, Gh, and Eth patients, respectively ( P = .008)., Conclusion: Extent of African ancestry seems to be associated with particular breast cancer phenotypes. West African ancestry correlates with increased risk of TNBC and breast cancers that are positive for ALDH1.

Breast cancer (BC) is the second leading cause of death among women in the US, and its subtype triple-negative BC (TNBC) is the most aggressive BC with poor prognosis. In the current study, we investigated the anticancer effects of the natural product plumbagin (PL) on racially different TNBC cells. The PL effects were examined in two TNBC cell lines: MDA-MB-231 (MM-231) and MDA-MB-468 (MM-468), representing Caucasian Americans and African Americans, respectively. The results obtained indicate that PL inhibited cell viability and cell proliferation and induced apoptosis in both cell lines. Notably, MM-468 cells were 5-fold more sensitive to PL than MM-231 cells were. Testing PL and Taxol® showed the superiority of PL over Taxol® as an antiproliferative agent in MM-468 cells. PL treatment resulted in an approximately 20-fold increase in caspase-3 activity with 3 μM PL in MM-468 cells compared with an approximately 3-fold activity increase in MM-231 cells with 8 μM PL. Moreover, the results indicate a higher sensitivity to PL in MM-468 cells than in MM-231 cells. The results also show that PL downregulated CCL2 cytokine expression in MM-468 cells by 30% compared to a 90% downregulation in MM-231 cells. The ELISA results confirmed the array data (35% vs. 75% downregulation in MM-468 and MM-231 cells, respectively). Moreover, PL significantly downregulated IL-6 and GM-CSF in the MM-231 cells. Indeed, PL repressed many NF-қB-regulated genes involved in the regulation of apoptosis, proliferation, invasion, and metastasis. The compound significantly downregulated the same genes (BIRC3, CCL2, TLR2, and TNF) in both types of cells. However, PL impacted five more genes in MM-231 cells, including BCL2A1, ICAM1, IKBKE, IL1β, and LTA. In conclusion, the data obtained in this study indicate that the quinone compound PL could be a novel cancer treatment for TNBC in African American women., Competing Interests: The authors have declared that no competing interests exist.

Background: Asians are diagnosed with breast cancer at a younger age than Caucasians are. We studied the effect of age on locoregional recurrence and the survival of Asian breast cancer patients treated with breast-conserving therapy., Methods: Medical records of 2492 patients treated with breast-conserving therapy between 1989 and 2012 were reviewed. The Kaplan-Meier method was used to estimate locoregional recurrence, breast cancer-free survival, and breast cancer-specific survival rates. These rates were then compared using log-rank tests. Outcomes and age were modeled by Cox proportional hazards. Fractional polynomials were then used to test for non-linear relationships between age and outcomes., Results: Patients ≤ 40 years old were more likely to have locoregional recurrence than were older patients (Hazard ratio [HR] = 2.32, P < 0.001). Locoregional recurrence rates decreased year-on-year by 4% for patients with luminal-type breast cancers, compared with 8% for those with triple-negative cancers. Similarly, breast cancer-free survival rates increased year-on-year by 4% versus 8% for luminal-type and triple-negative cancers, respectively. Breast cancer-specific survival rates increased with age by 5% year-on-year. Both breast cancer-free survival and breast cancer-specific survival rates in patients with luminal cancers exhibited a non-linear ("L-shaped") relationship-where decreasing age at presentation was associated with escalating risks of relapse and death. The influence of age on overall survival was confounded by competing non-cancer deaths in older women, resulting in a "U-shaped" relationship., Conclusions: Young Asian breast cancer patients have a continuous year-on-year increase in rates of disease relapse and cancer deaths compared with older patients with no apparent threshold.

To evaluate the clinical outcomes and relationship between tumor size, lymph node status, and prognosis in a large cohort of patients with triple-negative breast cancer (TNBC).849 Patients were categorized by tumor size and nodal status. The Kaplan-Meier method and Cox proportional hazards models were used to determine the association of nodal status and tumor size with survival outcomes. A Sidak adjustment was used for pairwise group comparisons. We conducted six pairwise comparisons between different node status. In univariate and multivariate analyses, it was indicated that N0 patients had similar prognoses as N1 patients (P = 0.072), and the OS of both of these groups was significantly better than that of N2/N3 patients (N0 vs N2, P < 0.001; N0 vs N3, P < 0.001; N1 vs N2, P = 0.014; N1 vs N3, P = 0.005). In summary, we report that in Chinese patients with triple-negative breast cancer, a greater difference in survival was observed between N1 and N2 than between N0 and N1, warranting the possible need of more intensive chemotherapy for N2-3 patients. We also found that tumor size made an impact on survival when lymph nodes were extensively involved, a finding that needs longer follow-up and further validation.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a high prevalence in blacks. South Carolina demographically has a high percentage of blacks. This study examines survival and recurrence associated with TNBC in black and white women. A retrospective review of breast cancer patients within the Palmetto Health Cancer Registry was performed from 1999 to 2015. Patient demographics and tumor characteristics were collected and correlated with outcomes. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed. The total number of breast cancer patients in the registry was 1723 (1085-white and 638-black). The median follow-up was 48.4 months. The majority of cancers diagnosed in both cohorts were early stage (I, IIA, IIB, 93.4% vs 90.4% P = NS). We identified 332 patients with TNBC. Of those 332 patients, 144 (43.4%) were whites and 188 (56.6%) were blacks. Older age (P = 0.01), high-grade (P < 0.001), and black race (P < 0.001) were significantly associated with TNBC on multivariate analysis. Five- and 10-year OS was significantly worse in blacks with TNBC (P < 0.001). There was no difference in DSS or RFS between the two cohorts. TNBC disproportionately affects black women and is an aggressive subtype of breast cancer with limited treatment options compared with receptor-positive breast cancer. Black patients with TNBC in our study had statistically worse OS. These findings are similar to what has been reported in the literature and prompts further research in newer targeted therapies.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer known to have poorer prognoses and lower survival rates compared with other types of breast cancer. In addition, TNBC is overrepresented in premenopausal African American women. Using grounded theory as the qualitative methodological approach, the present article elucidates unique biopsychosocial challenges and needs of young African American women with TNBC. A study group of six women with TNBC and a comparison group of six women with estrogen receptor-positive breast cancer were interviewed longitudinally over three time points throughout the cancer treatment trajectory. Major themes that were unique to the study group of women with TNBC include (a) longer, more aggressive treatment trajectories; (b) more difficult struggles with feminine identity; (c) the presence of fertility and parenting issues; (d) higher burdens of care; (e) barriers to separation and individuation as a maturation milestone; and (f) feeling out of place compared with peers. These themes provide a foundation to inform how social workers care for this underserved group of women.

Purpose: To assess the effect of marital status and the role of race/ethnicity on breast cancer specific mortality in women with triple negative breast cancer (TNBC)., Methods: The study utilized the California Cancer Registry to identify 22,812 cases of first primary female TNBC. Unadjusted Kaplan-Meier breast cancer specific survival was computed. Cox Proportional Hazards modeling was used to compute the adjusted risk of breast cancer specific mortality for women who were single, separated, divorced, and widowed when compared with women who were married. Models were adjusted for age, stage, tumor grade, SES, and treatment with surgery, chemotherapy, hormone therapy, and radiation therapy. Hazard ratios (HR) and 95% confidence intervals (CI) were reported., Results: Separated (HR: 1.45; 95% CI: 1.14-2.01) and widowed (HR: 1.39; 95%CI: 1.23-1.57) white women had a higher risk of mortality than white married women whereas single and divorced white women had the same risk of mortality. For Asian/Pacific Islanders (API), only single (HR: 1.55; 95% CI: 1.17-2.06) and divorced (HR:1.81; 95% CI:1.26-2.60) women had a higher risk of mortality than married women. Marital status had no influence on risk of mortality for either black or Hispanic women., Conclusions: The risk of mortality associated with marital status is dependent on race/ethnicity. Only white and API women with TNBC have a marital advantage.

Triple-negative breast cancer (TNBC) is a breast cancer subtype characterized by marked differences between White and Black/African-American women. We performed a systems-level analysis on datasets from The Cancer Genome Atlas to elucidate how the expression patterns of mRNAs are shaped by regulatory noncoding RNAs (ncRNA). Specifically, we studied isomiRs, that is, isoforms of miRNAs, and tRNA-derived fragments (tRF). In normal breast tissue, we observed a marked cohesiveness in both the ncRNA and mRNA layers and the associations between them. This cohesiveness was widely disrupted in TNBC. Many mRNAs become either differentially expressed or differentially wired between normal breast and TNBC in tandem with isomiR or tRF dysregulation. The affected pathways included energy metabolism, cell signaling, and immune responses. Within TNBC, the wiring of the affected pathways with isomiRs and tRFs differed in each race. Multiple isomiRs and tRFs arising from specific miRNA loci (e.g., miR-200c, miR-21, the miR-17/92 cluster, the miR-183/96/182 cluster) and from specific tRNA loci (e.g., the nuclear tRNA Gly and tRNA Leu , the mitochondrial tRNA Val and tRNA Pro ) were strongly associated with the observed race disparities in TNBC. We highlight the race-specific aspects of transcriptome wiring by discussing in detail the metastasis-related MAPK and the Wnt/β-catenin signaling pathways, two of the many key pathways that were found differentially wired. In conclusion, by employing a data- and knowledge-driven approach, we comprehensively analyzed the normal and cancer transcriptomes to uncover novel key contributors to the race-based disparities of TNBC. Significance: This big data-driven study comparing normal and cancer transcriptomes uncovers RNA expression differences between Caucasian and African-American patients with triple-negative breast cancer that might help explain disparities in incidence and aggressive character. Cancer Res; 78(5); 1140-54. ©2017 AACR ., (©2017 American Association for Cancer Research.)

This Guest Editorial highlights the reviews in the Race in Cancer Health Disparities Theme Issue that improve our understanding of the complex role of race in disparities in cancer frequency and outcome., (Published by Elsevier Inc.)

Background: Triple-negative breast cancers (TNBCs) are defined by their lack of oestrogen receptor, progesterone receptor and epidermal growth factor receptor 2. Although heterogeneous, the majority are aggressive and treatment options are limited. Caveolin acts as tumour suppressor or promoter depending on the cancer type., Aim: In this study, we aimed to determine if the expression levels of the candidate biomarker caveolin-1 on stromal or tumour cells were associated with clinicopathological parameters and disease outcomes in TNBCs from an ethnically diverse cohort of Asian women., Methods: Tumour specimens from 699 women with TNBC were subjected to immunohistochemical analysis of the frequency and intensity of caveolin-1 expression in tumour and stromal cells. A subset of 141 tumour samples also underwent Nanostring measurement of CAV1 mRNA. Results were correlated with clinicopathological parameters and disease outcomes., Results: Expression of caveolin-1 in stromal cells was observed in 14.4% of TNBC cases. TNBCs of the basal-like phenotype (85% of samples) were significantly more likely to exhibit stromal cell caveolin-1 expression (p=0.028), as were those with a trabecular growth pattern (p=0.007). Lack of stromal caveolin-1 expression in both TNBCs and those with the basal-like phenotype was significantly associated with worse overall survival (p=0.009 and p=0.026, respectively): accordingly, increasing mRNA levels of CAV1 in TNBC samples predicted better overall survival. Caveolin-1 expression on TNBC tumour cells was not associated with clinical outcome., Conclusion: Stromal, but not tumoural, caveolin-1 expression is significantly associated with survival in Asian women with TNBC., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Triple-negative breast cancers (TNBCs) are more common among African-ancestry populations, such as African Americans and western, sub-Saharan Africans, compared with European-ancestry populations. This phenotype prevalence contributes to disparities in breast cancer outcomes between African Americans and White Americans. Breast cancer stem cells represent the tumor subpopulation involved in metastatic virulence, and ongoing research seeks to characterize the extent to which TNBC versus non-TNBC stem cells may differ. This review summarizes the existing literature regarding TNBCs and stem cells as they pertain to the burden of breast cancer among African-ancestry populations. Additional research related to variations in somatic tumor genomics between the African-American and White-American populations is also summarized. This review furthermore explores the history of insights regarding breast cancer disparities related to racial/ethnic identity, socioeconomic status, and tumor biology., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: Triple-negative breast cancer (TNBC) is most prevalent in young women of African ancestry (WAA) compared to women of other ethnicities. Recent studies found a correlation between high expression of the transcription factor Kaiso, TNBC aggressiveness, and ethnicity. However, little is known about Kaiso expression and localization patterns in TNBC tissues of WAA. Herein, we analyze Kaiso expression patterns in TNBC tissues of African (Nigerian), Caribbean (Barbados), African American (AA), and Caucasian American (CA) women., Methods: Formalin-fixed and paraffin embedded (FFPE) TNBC tissue blocks from Nigeria and Barbados were utilized to construct a Nigerian/Barbadian tissue microarray (NB-TMA). This NB-TMA and a commercially available TMA comprising AA and CA TNBC tissues (AA-CA-YTMA) were subjected to immunohistochemistry to assess Kaiso expression and subcellular localization patterns, and correlate Kaiso expression with TNBC clinical features., Results: Nigerian and Barbadian women in our study were diagnosed with TNBC at a younger age than AA and CA women. Nuclear and cytoplasmic Kaiso expression was observed in all tissues analyzed. Analysis of Kaiso expression in the NB-TMA and AA-CA-YTMA revealed that nuclear Kaiso H scores were significantly higher in Nigerian, Barbadian, and AA women compared with CA women. However, there was no statistically significant difference in nuclear Kaiso expression between Nigerian versus Barbadian women, or Barbadian versus AA women., Conclusions: High levels of nuclear Kaiso expression were detected in patients with a higher degree of African heritage compared to their Caucasian counterparts, suggesting a role for Kaiso in TNBC racial disparity.

The aim of this article is to investigate the expression of E-cadherin (E-cad) and vascular endothelial growth factor (VEGF) in triple-negative breast cancer (TNBC) of Han and Uygur women patients in western China, and their relationship with clinical features of TNBC.Totally, 172 cases of Han TNBC patients and 79 cases of Uighur TNBC patients were enrolled. The expressions of E-cad and VEGF were detected with immunohistochemistry. The correlation of E-cad and VEGF expression with lymph node metastasis, TNM stage, and histological grade were analyzed. The 5-year disease-free survival rate of the 2 groups was also evaluated.There was no significant difference in the 5-year disease-free survival rate (P > .05) and the expression of E-cad between the 2 groups. The positive rate of VEGF in Han was significantly lower than that in Uygur (P < .05). The expression of E-cad was negatively correlated with lymph node metastasis, TNM stage, and histological grade (-1≤r < 1, P < .05). However, the expression of VEGF was positively correlated with lymph node metastasis and TNM staging (0 < r < 1, P < 0.05), but not with histological grading.The expression of E-cad and VEGF and their relationship with clinical features of TNBC suggest that Uygur TNBC patients might have different prognostic factors as compared with Han patients.

Background: Triple negative breast cancer (TNBC) tumors are estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor-negative. TNBC is responsive to chemotherapy, but chemotherapy might be underused in some patient subgroups. The goal of the present study was to characterize the patterns of chemotherapy use (uptake and completion) in TNBC patients., Patients and Methods: Women with primary invasive, nonmetastatic breast cancer were recruited in Washington, DC, and Detroit. Data were collected using a standardized telephone survey that captured sociocultural and health care process factors. Clinical data were abstracted from the medical records. We used χ 2 tests to access the association between the receipt of chemotherapy use (initiation and completion) and categorical variables, and t tests were used for continuous variables. Logistic regression models were used to evaluate the factors associated with chemotherapy uptake., Results: Women with TNBC (16% of sample) were more likely to be black than white (68% vs. 32%; P < .05). Among women with TNBC, 60% underwent chemotherapy. Chemotherapy uptake was greater for black than for white women (48.3% vs. 11.7%; P = .01) and in women without (vs. with) healthcare discrimination (35% vs. 25%; P = .04). In multivariable models, only race was associated with the receipt of chemotherapy. Black women were more likely to receive chemotherapy than were white women. The odds ratio of receiving chemotherapy by race was 4.1 (95% confidence interval, 1.3-13.1). Each 1-year increase in age was associated with a lower likelihood of chemotherapy completion (odds ratio, 0.9; 95% confidence interval, 0.826-0.981; P = .02). Women with at least some college were less likely to complete chemotherapy than were those with other education levels (P = .02)., Conclusion: A substantial number of TNBC patients failed to receive and/or complete chemotherapy. Differences in chemotherapy uptake by race and sociocultural factors diminished in multivariable models but age and stage remained significant. Suboptimal treatment among women with TNBC could contribute to adverse outcomes. Future investigations are necessary to assess whether the noninitiation and/or noncompletion of chemotherapy is clinically warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: "Precision medicine" is a concept that by utilizing modern molecular diagnostics, an effective therapy is accurately applied for each cancer patient to improve their survival rates. The treatment of triple-negative breast cancer (TNBC) remains a challenging issue. The aim of this study was to compare the molecular subtypes of triple-negative breast cancer (TNBC) between Taiwanese and Non-Asian women., Methods: GEO Datasets for non-Asian (12 groups, n = 1450) and Taiwanese (3 groups, n = 465) breast cancer, including 617 TNBC, were acquired, normalized and cluster analyzed. Then, using TNBC cell lines of different subtypes, namely, MDA-MB-468 (basal-like1, BL1), MDA-MB-231 (mesenchymal stem like, MSL), BT-549 (mesenchymal, M), MDA-MB-453 (luminal androgen receptor, LAR), and DU4475 (immunomodulatory, IM), real-time PCR in triplicate for 47 genes signatures were performed to validate the specificity of these subtypes., Results: The results showed that the percentage of TNBC subtypes in non-Asian women, namely, BL1, BL2, IM, M, MSL, and LAR was 13.56, 8.91, 16.80, 20.45, 8.30, and 11.13%, respectively. When data from Taiwanese were normalized and clustered, five TNBC subtypes, namely, BL (8.94%), IM (13.82%), M (22.76%), MSL (30.89%), and LAR (23.58%), were classified. Real-time PCR validated the specificity of these subtypes. Besides, the presence of interaction between IM- and MSL-subtypes suggests the involvement of tumor microenvironment in TNBC subtype classification., Conclusion: Our data suggested that there exist different presentations between non-Asian and Taiwanese TNBC subtypes, which provides important information when selection of therapeutic targets or designs for clinical trials for TNBC patients.

Importance: Variation in cancer incidence and outcome has well-documented correlations with racial/ethnic identity. In the United States, the possible genetic and ancestral hereditary explanations for these associations are confounded by socioeconomic, cultural, and lifestyle patterns. Differences in the breast cancer burden of African American compared with European/white American women represent one of the most notable examples of disparities in oncology related to racial/ethnic identity. Elucidating the source of these associations is imperative in achieving the promise of the national Precision Medicine Initiative., Observations: Population-based breast cancer mortality rates have been higher for African American compared with white American women since the early 1980s, largely reflecting declines in mortality that have been disproportionately experienced among white American patients and at least partly explained by the advent of endocrine therapy that is less effective in African American women because of the higher prevalence of estrogen receptor-negative disease. The increased risk of triple-negative breast cancer in African American women as well as western, sub-Saharan African women compared with white American, European, and east African women furthermore suggests that selected genetic components of geographically defined African ancestry are associated with hereditary susceptibility for specific patterns of mammary carcinogenesis. Disentangling health care access barriers, as well as reproductive, lifestyle, and dietary factors from genetic contributions to breast cancer disparities remains challenging. Epigenetics and experiences of societal inequality (allostatic load) increase the complexity of studying breast cancer risk related to racial/ethnic identity., Conclusions and Relevance: Oncologic anthropology represents a transdisciplinary field of research that can combine the expertise of population geneticists, multispecialty oncologists, molecular epidemiologists, and behavioral scientists to eliminate breast cancer disparities related to racial/ethnic identity and advance knowledge related to the pathogenesis of triple-negative breast cancer.

Purpose: The ER-/PR-/HER2- or triple-negative (TNBC) subtype is more prevalent among women who are young, black, Hispanic, and of lower SES. The purpose of this study is to determine if young age and low SES are associated with TNBC within four mutually exclusive race/ethnicities., Methods: The study identified 19,283 cases of TNBC and 89,089 of ER+/PR+/HER2- from the California Cancer Registry. Logistic regression analyses were conducted separately for whites, blacks, Hispanics, and Asian/Pacific Islanders (API) to compute the adjusted odds ratios (OR) for age and SES for the TNBC versus the ER+/PR+/HER2- subtype., Results: White (OR=1.37;1.23-1.53) and Hispanic and women (OR=1.35;1.17-1.56) 30-39 had increased odds of the TNBC when compared with women 50-59 of the same race/ethnicity. Black women under 40 had the same odds, and black women 40-49 had lower odds of the TNBC as black women 50-59. White, black, and Hispanic women 70 and older had decreased or the same odds of the TNBC as 50 to 59-year-old women. API women had a similar risk of TNBC at all ages. Lower SES was associated with increased risk of TNBC only for white and Hispanic women. The odds of TNBC were no worse for API women with lower SES than API women with higher SES. SES was not statistically significant for black women., Conclusions: When assessing the odds of TNBC within a single race/ethnicity, young age and low SES are risk factors only for white and Hispanic women, but not for black and API women.

Background: Roma (Gypsies) constitute one of the largest ethnic minorities in Slovakia. Some reports have supported a higher prevalence of communicable diseases in Roma but data on cancer prevalence in Roma is absent. The aim of this study was to compare differences in the incidence and pathological characteristics of breast cancer between Roma and non-Roma in Slovakia., Patients and Methods: Roma and non-Roma breast cancer patients were identified using the Slovak HER2 Registry. The database from the last Census of Slovakia in 2011 was matched by gender, date of birth, and residency with the HER2 Registry from 2011 to 2013. Based on the match, Roma and non-Roma breast cancer patients were identified., Results: Thirty-two and 5,775 women with breast cancer were identified as Roma and non-Roma, resp. The age-standardized breast cancer incidence rate was 2.12 times higher for non-Roma than for Roma patients (36 vs. 17 per 100,000 people). Roma patients were younger than non-Roma patients (median 49 vs. 61 years; p = 0.00001). Roma patients had more hormone receptor negative (34.4% vs. 18.1%; p = 0.03) and triple negative tumors (28.1% vs. 12.3%; p = 0.01) than non-Roma, and these differences remained statistically significant in multivariate analysis., Conclusion: For the first time, this study has revealed that the incidence and biological characteristics of breast cancer are different between Roma and non-Roma. Our data suggests that Roma patients are younger at diagnosis, have a lower age-standardized breast cancer incidence rate, and have more aggressive tumors than non-Roma.