Comprehensive omic characterization of breast cancer in Mexican-Hispanic women.
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ABSTRACT:
SUBMITTER: Romero-Cordoba SL
PROVIDER: S-EPMC8046804 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Evaluating breast cancer outcomes specific to Hispanics of different race (e.g. Hispanic Black, Hispanic White) may further explain variations in the burden of breast cancer among Hispanic women. Using data from the SEER 17 population-based registries, we evaluated the association between race/ethnicity and tumor stage, hormone receptor status, and breast cancer-specific mortality. The study cohort of 441,742 women, aged 20-79, who were diagnosed with primary invasive breast cancer between January 1, 1992 and December 31, 2008, included 44,246 Hispanic whites, 622 Hispanic Blacks, 44,797 non-Hispanic Blacks and 352,077 non-Hispanic whites. Hispanic black, Hispanic white and non-Hispanic black women had a 1.5-2.5 fold greater risk of presenting with stage IV breast cancer compared to non-Hispanic whites. All groups were significantly more likely than non-Hispanic whites to be diagnosed with ER+/PR- (1.1-1.5 fold increase) or ER-/PR- (1.4-2.2 fold increase) breast cancer. Hispanic black, Hispanic white and non-Hispanic black women had a 10-50 % greater risk of breast cancer-specific mortality compared to non-Hispanic whites. Our findings underscore the breast cancer disparities that continue to exist for Hispanic and black women, overall, as well as between Hispanic women of different race. These disparities highlight the factors that may lead to the poor outcomes observed among Hispanic and black women diagnosed with breast cancer, and for which targeted strategies aimed at reducing breast cancer disparities could be developed.
| S-EPMC3903405 | biostudies-literature
Project description:For Hispanic women, the Breast Cancer Risk Assessment Tool (BCRAT; "Gail Model") combines 1990-1996 breast cancer incidence for Hispanic women with relative risks for breast cancer risk factors from non-Hispanic white (NHW) women. BCRAT risk projections have never been comprehensively evaluated for Hispanic women. We compared the relative risks and calibration of BCRAT risk projections for 6,353 Hispanic to 128,976 NHW postmenopausal participants aged 50 and older in the Women's Health Initiative (WHI). Calibration was assessed by the ratio of the number of breast cancers observed with that expected by the BCRAT (O/E). We re-evaluated calibration for an updated BCRAT that combined BCRAT relative risks with 1993-2007 breast cancer incidence that is contemporaneous with the WHI. Cox regression was used to estimate relative risks. Discriminatory accuracy was assessed using the concordance statistic (AUC). In the WHI Main Study, the BCRAT underestimated the number of breast cancers by 18% in both Hispanics (O/E = 1.18, P = 0.06) and NHWs (O/E = 1.18, P < 0.001). Updating the BCRAT improved calibration for Hispanic women (O/E = 1.08, P = 0.4) and NHW women (O/E = 0.98, P = 0.2). For Hispanic women, relative risks for number of breast biopsies (1.71 vs. 1.27, P = 0.03) and age at first birth (0.97 vs. 1.24, P = 0.02) differed between the WHI and BCRAT. The AUC was higher for Hispanic women than NHW women (0.63 vs. 0.58, P = 0.03). Updating the BCRAT with contemporaneous breast cancer incidence rates improved calibration in the WHI. The modest discriminatory accuracy of the BCRAT for Hispanic women might improve by using risk factor relative risks specific to Hispanic women.
| S-EPMC3827770 | biostudies-literature
Project description:The use of hormonal therapies, including hormonal contraceptives (HC) and postmenopausal hormone replacement therapy (HRT) have been shown to influence breast cancer (BC) risk. However, the variations of these effects among populations and ethnic groups are not completely documented, especially among Hispanic women. We evaluated the association between HC and premenopausal BC risk, and between HRT and postmenopausal BC risk in Mexican women. Data from a Mexican multi-center population-based case-control study ofwomen aged 35 to 69 years were analysed. A total of 1000 cases and 1074 matched controls were recruited between 2004 and 2007. Information on hormonal therapy was collected through a structured questionnaire. Results were analysed using conditional logistic regression models. Overall, HC were used by 422/891 (47.3%) premenopausal women and HRT was used by 220/1117 (19.7%) postmenopausal women. For HC, odds ratios (ORs) for BC were 1.11 (95% confidence interval (CI): 0.82, 1.49) for current users and 1.68 (95% CI: 0.67, 4.21) for ever-users. No clear effect of duration of use was observed. For HRT, the OR for BC was significantly increased in ever users (OR: 1.45; 95% CI: 1.01, 2.08). A non-significant increased risk was observed for combined estrogen/progestin, (OR = 1.85; 95% CI: 0.84, 4.07) whereas no effect was observed for the use of estrogen alone (OR = 1.14; 95% CI: 0.68, 1.91). Our results indicate that, HC had a non-significant effect on the risk of pre-menopausal BC, but suggested that injected contraceptives may slightly increase the risk, whereas HRT had a significant effect on post-menopausal BC in this population. This study provides new information about the effects of HC and HRT on BC risk in a Mexican population, which may be of relevance for the population of Latin America as a whole.
| S-EPMC3829873 | biostudies-other
Project description:The risk of breast cancer transiently increases immediately following pregnancy; peaking between 3-7 years. The biology that underlies this risk window and the effect on the natural history of the disease is unknown. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to be dysregulated in breast cancer. We conducted miRNA profiling of 56 tumors from a case series of multiparous Hispanic women and assessed the pattern of expression by time since last full-term pregnancy. A data-driven splitting analysis on the pattern of 355 miRNAs separated the case series into two groups: a) an early group representing women diagnosed with breast cancer ? 5.2 years postpartum (n = 12), and b) a late group representing women diagnosed with breast cancer ? 5.3 years postpartum (n = 44). We identified 15 miRNAs with significant differential expression between the early and late postpartum groups; 60% of these miRNAs are encoded on the X chromosome. Ten miRNAs had a two-fold or higher difference in expression with miR-138, miR-660, miR-31, miR-135b, miR-17, miR-454, and miR-934 overexpressed in the early versus the late group; while miR-892a, miR-199a-5p, and miR-542-5p were underexpressed in the early versus the late postpartum group. The DNA methylation of three out of five tested miRNAs (miR-31, miR-135b, and miR-138) was lower in the early versus late postpartum group, and negatively correlated with miRNA expression. Here we show that miRNAs are differentially expressed and differentially methylated between tumors of the early versus late postpartum, suggesting that potential differences in epigenetic dysfunction may be operative in postpartum breast cancers.
| S-EPMC4395255 | biostudies-literature
Project description:BackgroundBreast cancer cell lines are frequently used as model systems to study the cellular properties and biology of breast cancer. Our objective was to characterize a large, commonly employed panel of breast cancer cell lines obtained from the American Type Culture Collection (ATCC 30-4500 K) to enable researchers to make more informed decisions in selecting cell lines for specific studies. Information about these cell lines was obtained from a wide variety of sources. In addition, new information about cellular pathways that are activated within each cell line was generated.MethodsWe determined key protein expression data using immunoblot analyses. In addition, two analyses on serum-starved cells were carried out to identify cellular proteins and pathways that are activated in these cells. These analyses were performed using a commercial PathScan array and a novel and more extensive phosphopeptide-based kinome analysis that queries 1290 phosphorylation events in major signaling pathways. Data about this panel of breast cancer cell lines was also accessed from several online sources, compiled and summarized for the following areas: molecular classification, mRNA expression, mutational status of key proteins and other possible cancer-associated mutations, and the tumorigenic and metastatic capacity in mouse xenograft models of breast cancer.ResultsThe cell lines that were characterized included 10 estrogen receptor (ER)-positive, 12 human epidermal growth factor receptor 2 (HER2)-amplified and 18 triple negative breast cancer cell lines, in addition to 4 non-tumorigenic breast cell lines. Within each subtype, there was significant genetic heterogeneity that could impact both the selection of model cell lines and the interpretation of the results obtained. To capture the net activation of key signaling pathways as a result of these mutational combinations, profiled pathway activation status was examined. This provided further clarity for which cell lines were particularly deregulated in common or unique ways.ConclusionsThese two new kinase or "Kin-OMIC" analyses add another dimension of important data about these frequently used breast cancer cell lines. This will assist researchers in selecting the most appropriate cell lines to use for breast cancer studies and provide context for the interpretation of the emerging results.
| S-EPMC5460504 | biostudies-literature
Project description:The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, functions in cellular processes essential to the development of cancer. Overexpression of EGFR in primary breast tumors has been linked with poor prognosis. We investigated the associations between 34 EGFR tagging SNPs and breast cancer risk and breast cancer-specific mortality in 4,703 Hispanic and 3,030 non-Hispanic white women from the Breast Cancer Health Disparities Study. We evaluated associations with risk of breast cancer defined by estrogen/progesterone receptor (ER/PR) tumor phenotype. Only one association remained statistically significant after adjusting for multiple comparisons. Rs2075112GA/AA was associated with reduced risk for ER-/PR+ tumor phenotype (odds ratio (OR), 0.34; 95% confidence interval (CI) 0.18-0.63, p adj=0.01). All additional results were significant prior to adjustment for multiple comparisons. Two of the EGFR polymorphisms were associated with breast cancer risk in the overall study population (rs11770531TT: OR, 0.56, 95% CI 0.37-0.84; and rs2293348AA: OR, 1.20, 95% CI 1.04-1.38) and two polymorphisms were associated with risk among Hispanics: rs6954351AA: OR, 2.50, 95% CI 1.32-4.76; and rs845558GA/AA: OR, 1.15, 95% CI 1.01-1.30. With regard to breast cancer-specific mortality, we found positive associations with rs6978771TT hazard ratio (HR), 1.68; 95% CI 1.11-2.56; rs9642391CC HR, 1.64; 95% CI 1.04-2.58; rs4947979AG/GG HR, 1.36; 95% CI 1.03-1.79; and rs845552GG HR, 1.62; 95% CI 1.05-2.49. Our findings provide additional insight for the role of EGFR in breast cancer development and prognosis. Further research is needed to elucidate EGFR's contribution to ethnic disparities in breast cancer.
| S-EPMC3852643 | biostudies-literature
Project description:The transcription factor 7-like 2 (TCF7L2) gene is part of the Wnt/β-catenin signaling pathway and plays a critical role in cell development and growth regulation. TCF7L2 variants rs12255372 and rs7903146 have been associated with risk of Type 2 diabetes. Few epidemiological studies have examined the association between TCF7L2 and breast cancer risk. We investigated the associations between 25 TCF7L2 single nucleotide polymorphisms (SNPs) and breast cancer in Hispanic and non-Hispanic white (NHW) women from the 4-Corner's Breast Cancer Study, the San Francisco Bay Area Breast Cancer Study, and the Mexico Breast Cancer Study. A total of 4,703 Hispanic (2,093 cases, 2,610 controls) and 3,031 NHW (1,431 cases, 1,600 controls) women were included. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated using logistic regression to estimate the association between the TCF7L2 SNPs and breast cancer risk. We also examined effect modification by self-reported ethnicity, genetic admixture, and diabetes history. After adjusting for multiple comparisons, four TCF7L2 SNPs were significantly associated with breast cancer overall: rs7903146 (OR(TT) 1.24; 95 % CI 1.03-1.49), rs3750805 (OR(AT/TT) 1.15; 95 % CI 1.03-1.28), rs7900150 (OR(AA) 1.23; 95 % 1.07-1.42), and rs1225404 (OR(CC) 0.82; 95 % 0.70-0.94). Among women with a history of diabetes, the TT genotype of rs3750804 increased breast cancer risk (OR, 2.46; 95 % CI 1.28-4.73). However, there was no association among women without a diabetes history (OR, 1.06; 95 % CI 0.85-1.32). We did not find significant interactions by ethnicity or by genetic admixture. Findings support an association between TCF7L2 and breast cancer and history of diabetes modifies this association for specific variants.
| S-EPMC3662467 | biostudies-literature
Project description:BackgroundHispanic/Latina women are less likely to be diagnosed with local stage breast cancer than White women. Additionally, foreign-born women have lower mammography rates than US-born women. We evaluated the combined effect of birthplace and race/ethnicity on screening habits of women at higher-than-average risk of breast cancer.MethodsMultinomial logistic regression was used to evaluate breast cancer screening in 44,524 women in the Sister Study cohort. Screening methods ascertained at enrollment (2003-2009) included mammography, ultrasound, and magnetic resonance imaging. Timing of screening was assessed as recently (≤2 years ago), formerly (>2 years ago), and never screened. Adjustments included sociodemographic, socioeconomic, and health variables.ResultsMost women in the sample were US-born non-Hispanic/Latina White (92%), were ≥50 years old (73%), had one first-degree female relative with breast cancer (73%), and were screened in the past two years (97%). US-born Hispanic/Latina women had higher odds (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.08-2.00) than US-born non-Hispanic/Latina White women of not having received a breast cancer screening in the past 2 years, relative to a recent screening. Similarly, foreign-born Hispanic/Latina women had higher odds (OR = 1.63, 95% CI = 1.10-2.41) than US-born non-Hispanic/Latina White women of never having received a breast cancer screening.ConclusionWe observed that Hispanic/Latina women have higher odds of never and dated breast cancer screenings compared to US-born White women. Birthplace and race/ethnicity each contribute to disparities in who receives preventative health care in the United States. It is critical to include birthplace when evaluating health behaviors in minority groups.
| S-EPMC9041086 | biostudies-literature
Project description:BackgroundThere is no model to estimate absolute invasive breast cancer risk for Hispanic women.MethodsThe San Francisco Bay Area Breast Cancer Study (SFBCS) provided data on Hispanic breast cancer case patients (533?US-born, 553 foreign-born) and control participants (464?US-born, 947 foreign-born). These data yielded estimates of relative risk (RR) and attributable risk (AR) separately for US-born and foreign-born women. Nativity-specific absolute risks were estimated by combining RR and AR information with nativity-specific invasive breast cancer incidence and competing mortality rates from the California Cancer Registry and Surveillance, Epidemiology, and End Results program to develop the Hispanic risk model (HRM). In independent data, we assessed model calibration through observed/expected (O/E) ratios, and we estimated discriminatory accuracy with the area under the receiver operating characteristic curve (AUC) statistic.ResultsThe US-born HRM included age at first full-term pregnancy, biopsy for benign breast disease, and family history of breast cancer; the foreign-born HRM also included age at menarche. The HRM estimated lower risks than the National Cancer Institute's Breast Cancer Risk Assessment Tool (BCRAT) for US-born Hispanic women, but higher risks in foreign-born women. In independent data from the Women's Health Initiative, the HRM was well calibrated for US-born women (observed/expected [O/E] ratio = 1.07, 95% confidence interval [CI] = 0.81 to 1.40), but seemed to overestimate risk in foreign-born women (O/E ratio = 0.66, 95% CI?=?0.41 to 1.07). The AUC was 0.564 (95% CI?=?0.485 to 0.644) for US-born and 0.625 (95% CI?=?0.487 to 0.764) for foreign-born women.ConclusionsThe HRM is the first absolute risk model that is based entirely on data specific to Hispanic women by nativity. Further studies in Hispanic women are warranted to evaluate its validity.
| S-EPMC5174188 | biostudies-literature
Project description:PURPOSE:There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women. METHODS:The study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case-control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels. RESULTS:When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05-1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95% CI 1.18-1.71; trend p < 0.001), and between white meat (OR 0.80; 95% CI 0.67-0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models and were restricted to estrogen receptor-positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups. CONCLUSIONS:Our results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities.
| S-EPMC4821634 | biostudies-literature