Insulin resistance contributes to racial disparities in breast cancer prognosis in US women.
Ontology highlight
ABSTRACT:
SUBMITTER: Gallagher EJ
PROVIDER: S-EPMC7216707 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
Publications
Insulin resistance contributes to racial disparities in breast cancer prognosis in US women.
Gallagher Emily J EJ Fei Kezhen K Feldman Sheldon M SM Port Elisa E Friedman Neil B NB Boolbol Susan K SK Killelea Brigid B Pilewskie Melissa M Choi Lydia L King Tari T Nayak Anupma A Franco Rebeca R Cruz Daliz D Antoniou Irini M IM LeRoith Derek D Bickell Nina A NA
Breast cancer research : BCR 20200512 1
<h4>Background</h4>Racial disparities in breast cancer survival between Black and White women persist across all stages of breast cancer. The metabolic syndrome (MetS) of insulin resistance disproportionately affects more Black than White women. It has not been discerned if insulin resistance mediates the link between race and poor prognosis in breast cancer. We aimed to determine whether insulin resistance mediates in part the association between race and breast cancer prognosis, and if insulin ...[more]
Similar Datasets
Project description:PurposeEarly diagnosis is fundamental to reducing breast cancer (BC) mortality, and understanding potential barriers from initial screening to confirmed diagnosis is essential. The aim of this study was to evaluate patient characteristics that contribute to delay in diagnosis of screen-detected cancers and the contribution of delay to tumor characteristics and BC mortality.MethodsThree hundred sixty-two White and 368 Black women were identified who were screened and received subsequent BC diagnoses within Emory Healthcare, a part of Emory University health care system (2010-2014). Multivariable-adjusted logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) associating patient characteristics with delay to diagnostic evaluation (≥30 versus <30 days), delay to biopsy (≥15 versus <15 days), and total delay (≥45 versus <45 days). Additionally, the ORs and 95% CIs associating delay with tumor characteristics and BC mortality were computed.ResultsBlack women and women diagnosed at later stages, with larger tumor sizes, and with triple-negative tumors were more likely to experience ≥45 days to diagnosis. In multivariable-adjusted models, Black women had at least a two-fold increase in the odds of delay to diagnostic evaluation (OR, 1.98; 95% CI, 1.45-2.71), biopsy delays (OR, 2.41; 95% CI, 1.67-3.41), and total delays ≥45 days (OR, 2.22; 95% CI, 1.63-3.02) compared with White women. A 1.6-fold increased odds of BC mortality was observed among women who experienced total delays ≥45 days compared with women without delays in diagnosis (OR, 1.57, 95% CI, 0.96-2.58).ConclusionsThe study demonstrated racial disparities in delays in the diagnostic process for screen-detected malignancies. Total delay in diagnosis was associated with an increase in BC mortality.
| S-EPMC8492512 | biostudies-literature
Project description:African-American women are more likely than white women to have functional impairments after breast cancer (BC) surgery; however, no differences were found in self-reported health status surveys at 12+ months postsurgery.This analysis compared white and African-American BC survivors' (BCS) health status, health-related quality of life, and the occurrence of physical impairments after BC treatment.One hundred sixty-six women (130 white, 28 African-American, 8 other) were assessed for impairments preoperatively and at 1, 3, 6, 9, and 12+ months postsurgery. Health status was assessed at 12+ months using the Short Form Health Survey (SF36v2™). Analysis of variance estimated differences between groups for health status and impairment occurrence.No differences were found between groups for BC type, stage, grade, or tumor size; surgery type; or number of lymph nodes sampled. African-American BCS had more estrogen/progesterone receptor-negative tumors (p < 0.001; p = 0.036) and received radiation more frequently (p = 0.03). More African-American BCS were employed (p = 0.022) and reported higher rates of social activities (p = 0.011) but less recreational activities (p = 0.020) than white BCS. African-American BCS had higher rates of cording (p = 0.013) and lymphedema (p = 0.011) postoperatively. No differences were found in self-reported health status.In a military healthcare system, where access to care is ubiquitous, there were no significant differences in many BC characteristics commonly attributed to race. African-American women had more ER/PR-negative tumors; however, no other BC characteristics differed between racial groups. African-American women exhibited more physical impairments, although their BC treatment only differed regarding radiation therapy. This suggests that African-American BCS may be at higher risk for physical impairments and should be monitored prospectively for early identification and treatment.
| S-EPMC5558212 | biostudies-other
Project description:Breast cancer stem cells (BCSCs) promote endocrine therapy (ET) resistance, also known as endocrine resistance in hormone receptor (HR) positive breast cancer. Endocrine resistance occurs via mechanisms that are not yet fully understood. In vitro, in vivo and clinical data suggest that signaling cascades such as Notch, hypoxia inducible factor (HIF), and integrin/Akt promote BCSC-mediated endocrine resistance. Once HR positive breast cancer patients relapse on ET, targeted therapy agents such as cyclin dependent kinase inhibitors are frequently implemented, though secondary resistance remains a threat. Here, we discuss Notch, HIF, and integrin/Akt pathway regulation of BCSC activity and potential strategies to target these pathways to counteract endocrine resistance. We also discuss a plausible link between elevated BCSC-regulatory gene levels and reduced survival observed among African American women with basal-like breast cancer which lacks HR expression. Should future studies reveal a similar link for patients with luminal breast cancer, then the use of agents that impede BCSC activity could prove highly effective in improving clinical outcomes among African American breast cancer patients.
| S-EPMC7872014 | biostudies-literature
Project description:The cardiotoxic effects of breast cancer therapies are well documented in clinical trials. However, clinical trials often underrepresent those at highest risk for cardiovascular disease (CVD)related outcomes and have limited generalizability to the larger breast cancer population. In addition, racial differences in treatment-associated CVD mortality have yet to be explored. In this study, we sought to quantify the relationship between breast cancer therapies and CVD mortality, and explore whether this effect differed between non-Hispanic black (NHB) and white (NHW) women. Using data from the Georgia Cancer Registry, we identified women diagnosed with a first primary invasive breast cancer [2010-2014], residing in the metropolitan Atlanta area (n=3,580 NHB; n=4,923 NHW), and followed them for mortality through December 31, 2018. Exposures of interest included therapies with potential cardiotoxic effects including chemotherapy and hormone therapy, which are routinely collected by the GCR. Individual agents are not captured within the GCR, therefore trastuzumab was identified using natural language processing of textual descriptions. We used propensity score weighted Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between each treatment modality and CVD mortality among the overall cohort and by race. In the overall cohort, similar hazards of CVD mortality were found among women treated with chemotherapy (HR =1.10, 95% CI: 0.62, 1.96) and hormone therapy (HR =0.94, 95% CI: 0.59, 1.50), compared to women who did not receive the respective treatments. In contrast, women treated with trastuzumab had a higher hazard of CVD mortality compared to women not treated with trastuzumab (HR =2.05, 95% CI: 0.76, 5.52). In race-specific models, hormone therapy was associated with a higher hazard of CVD mortality among NHB women (HR =2.18, 95% CI: 0.78, 6.12), but not NHW women (HR =0.66, 95% CI: 0.39, 1.13). Similar, albeit attenuated, associations were found for chemotherapy. We were unable to investigate race-specific effects of trastuzumab due to low prevalence and insufficient number of events. In our study, we observed more pronounced associations of chemotherapy and hormone therapy with CVD mortality among NHB women, for whom we know have greater CVD-related comorbidities at breast cancer diagnosis. Patients may benefit from treatment plans that find a balance between curative breast cancer treatment and prevention of CVD-related events and mortality. CVD-related outcomes may be most relevant for women with hormone receptor positive disease due to shared risk factors (e.g., obesity, tobacco use, physical activity) and longer survival.
| S-EPMC7497843 | biostudies-literature
Project description:PurposeTumors of the inner quadrants of the breast are associated with poorer survival than those of the upper-outer quadrant. It is unknown whether racial differences in breast cancer outcomes are modified by breast quadrant, in addition to comparisons among Asian subgroups.MethodsUsing the Surveillance, Epidemiology, and End Results database, we analyzed data among women diagnosed with non-metastatic invasive breast cancer between 1990 and 2014. We performed Cox proportional hazards regression models to assess the associations of race with breast cancer-specific survival and overall survival, stratified by breast quadrants. The models were adjusted for age, year of the diagnosis, tumor size, grade, histological type, tumor laterality, lymph node, estrogen receptor, progesterone receptor, and treatments.ResultsAmong 454,154 patients (73.0% White, 10.0% Black, 7.8% Asian/PI, and 9.2% Hispanic), 54.3% had tumors diagnosed in the upper-outer quadrant of the breast. Asian/PI women were more likely than White to have tumors diagnosed in the nipple/central portion of the breast and were less likely to have diagnosed in the upper-outer quadrant (P < 0.001), despite a similar distribution of breast quadrant between Black, Hispanic, and White women. Compared with White women, the multivariable-adjusted hazard ratios of breast cancer-specific mortality were 1.41 (95% CI 1.37-1.44) in Black women, 0.82 (95% CI 0.79-0.85) in Asian women, and 1.05 (95% CI 1.02-1.09) in Hispanic women. Among Asian subgroups, Japanese American women had a lower risk of breast cancer-specific mortality (HR = 0.68, 95% CI 0.62-0.74) compared with White women. Overall survival was similar to breast cancer-specific survival in each race group. The race-associated risks did not vary significantly by breast quadrants for breast cancer-specific mortality and all-cause mortality.ConclusionsDifferences in breast cancer survival by race could not be attributed to tumor locations. Understanding the cultural, biological, and lifestyle factors that vary between White, African American, and ethnic subgroups of Asian American women may help explain these survival differences.
| S-EPMC6924513 | biostudies-literature
Project description:Breast cancer (BCa) has long been a health burden to women across the globe. However, the burden is not equally carried across races. Though the manifestation and behavior of BCa differs among racial groups, the racial representation of models used in preclinical trials and clinical trial participants lacks this heterogeneity. Women of African Ancestry (WAA) are disproportionately afflicted by having an increased risk of developing BCas that are more aggressive in nature, and consequently suffer from poorer outcomes relative to women of European ancestry (WEA). Notwithstanding this, one of the most commonly used tools in studying BCa, cell lines, exhibit a sizeable gap in cell line derivatives of WEA relative to WAA. In this review, we summarize the available BCa cell lines grouped by race by major suppliers, American Type Culture Collection (ATCC) and the European Collection of Authenticated Cell Cultures (ECACC). Next, examined the enrollment of WAA in clinical trials for BCa. Of the cell lines found provided by ATCC and ECACC, those derived from WEA constituted approximately 80% and 94%, respectively. The disparity is mirrored in clinical trial enrollment where, on average, WEA made up more than 70% of participants in trials found where ancestry information was provided. As both experimental models and clinical trial participants primarily consist of WEA, results may have poorer translatability toward other races. This highlights the need for greater racial diversity at the preclinical and clinical levels to more accurately represent the population and strengthen the translatability of results.
| S-EPMC9354441 | biostudies-literature
Project description:BACKGROUND:Human epidermal growth factor receptor 2 (HER2)-targeted therapies are highly effective at preventing breast cancer recurrence but are associated with cardiotoxicity in some patients, and minimal data are available regarding racial disparities in the incidence of this toxicity. The authors conducted a retrospective study to analyze the association of black or white race with treatment-induced cardiotoxicity and incomplete therapy among patients with HER2-positive early breast cancer. METHODS:Women with HER2-positive, stage I through III breast cancer who initiated (neo)adjuvant HER2-targeted therapy (trastuzumab with or without pertuzumab) from January 2005 to March 2015 at the authors' institution were eligible. We analyzed differences in the incidence of cardiotoxicity (a decline in the left ventricular ejection fraction to <50% AND an absolute drop in the left ventricular ejection fraction of ?10% from baseline) and incomplete therapy (<52 weeks of HER2-targeted therapy) between black and white women in univariate and multivariable analyses. RESULTS:The authors identified 59 black patients and 157 white patients who had a median follow-up 5.2 years. The median patient age was 53 years and was similar for black and white patients. The 1-year cardiotoxicity incidence was 12% overall (95% confidence interval [CI], 7%-16%), 24% in black women (95% CI, 12%-34%), and 7% in white women (95% CI, 3%-11%). Black patients had a significantly greater probability of incomplete therapy compared with white patients (odds ratio, 4.61; 95% CI, 1.70-13.07; P = .002). High correlation was observed between a cardiotoxicity event and incomplete therapy (96% concordance). CONCLUSIONS:Black patients have a higher rate of cardiotoxicity and resultant incomplete adjuvant HER2-targeted therapy than white patients. This patient population may benefit from enhanced cardiac surveillance, cardioprotective strategies, and early referral to cardiology when appropriate. Cancer 2018;124:1904-11. © 2018 American Cancer Society.
| S-EPMC5910274 | biostudies-literature
Project description:PurposeRacial disparities in BRCA1/2 testing have been documented, but causes of these disparities are poorly understood. The study objective was to investigate whether the distribution of black and white patients across cancer providers contributes to disparities in BRCA1/2 testing.Patients and methodsWe conducted a population-based study of women in Pennsylvania and Florida who were 18 to 64 years old and diagnosed with invasive breast cancer between 2007 and 2009, linking cancer registry data, the American Medical Association Physician Masterfile, and patient and physician surveys. The study included 3,016 women (69% white, 31% black), 808 medical oncologists, and 732 surgeons.ResultsBlack women were less likely to undergo BRCA1/2 testing than white women (odds ratio [OR], 0.40; 95% CI, 0.34 to 0.48; P < .001). This difference was attenuated but not eliminated by adjustment for mutation risk, clinical factors, sociodemographic characteristics, and attitudes about testing (OR, 0.66; 95% CI, 0.53 to 0.81; P < .001). The care of black and white women was highly segregated across surgeons and oncologists (index of dissimilarity 64.1 and 61.9, respectively), but adjusting for clustering within physician or physician characteristics did not change the size of the testing disparity. Black women were less likely to report that they had received physician recommendation for BRCA1/2 testing even after adjusting for mutation risk (OR, 0.66; 95% CI, 0.54 to 0.82; P < .001). Adjusting for physician recommendation further attenuated the testing disparity (OR, 0.76; 95% CI, 0.57 to 1.02; P = .06).ConclusionAlthough black and white patients with breast cancer tend to see different surgeons and oncologists, this distribution does not contribute to disparities in BRCA1/2 testing. Instead, residual racial differences in testing after accounting for patient and physician characteristics are largely attributable to differences in physician recommendations. Efforts to address these disparities should focus on ensuring equity in testing recommendations.
| S-EPMC5012689 | biostudies-literature
Project description:The multifaceted involvement of centrosome amplification (CA) in tumorigenesis is coming into focus following years of meticulous experimentation, which have elucidated the powerful abilities of CA to promote cellular invasion, disrupt stem cell division, drive chromosomal instability (CIN) and perturb tissue architecture, activities that can accelerate tumor progression. Integration of the extant in vitro, in vivo and clinical data suggests that in some tissues CA may be a tumor-initiating event, in others a consequential 'hit' in multistep tumorigenesis, and in some others, non-tumorigenic. However, in vivo data are limited and primarily focus on PLK4 (which has CA-independent mechanisms by which it promotes aggressive cellular phenotypes). In vitro breast cancer models suggest that CA can promote tumorigenesis in breast cancer cells in the setting of p53 loss or mutation, which can both trigger CA and promote cellular tolerance to its tendency to slow proliferation and induce aneuploidy. It is thus our perspective that CA is likely an early hit in multistep breast tumorigenesis that may sometimes be lost to preserve aggressive karyotypes acquired through centrosome clustering-mediated CIN, both numerical and structural. We also envision that the robust link between p53 and CA may underlie, to a considerable degree, racial health disparity in breast cancer outcomes. This question is clinically significant because, if it is true, then analysis of centrosomal profiles and administration of centrosome declustering drugs could prove highly efficacious in risk stratifying breast cancers and treating African American (AA) women with breast cancer.
| S-EPMC5837860 | biostudies-literature
Project description:ImportanceRacial disparities exist in many aspects of breast cancer care. Sentinel lymph node biopsy (SLNB) was developed to replace axillary lymph node dissection (ALND) for staging early breast cancer to minimize complications. Racial disparities in the use of SLNB remain incompletely characterized, and their effect on lymphedema risk is not known.ObjectiveTo determine racial differences in SLNB use among patients with pathologically node-negative breast cancer during the period when SLNB became the preferred method for axillary staging as well as whether such differences affect lymphedema risk.Design, setting, and participantsA retrospective study was conducted using the Surveillance, Epidemiology, and End Results-Medicare-linked database from 2002 through 2007 to identify cases of incident, nonmetastatic, pathologically node-negative breast cancer in women aged 66 years or older.Main outcomes and measuresSentinel lymph node biopsy use and 5-year cumulative incidence of lymphedema by race.ResultsOf 31 274 women identified, 1767 (5.6%) were black, 27 856 (89.1%) were white, and 1651 (5.3%) were of other or unknown race. Sentinel lymph node biopsy was performed in 73.7% of white patients and 62.4% of black patients (P < .001). The use of SLNB increased by year for both black and white patients (P < .001); however, a fixed disparity of approximately 12 percentage points in SLNB use persisted through 2007. In adjusted analysis, black patients were significantly less likely than white patients to undergo SLNB (odds ratio, 0.67; 95% CI, 0.60-0.75; P < .001). Overall, the 5-year cumulative lymphedema risk was 8.2% in whites and 12.3% in blacks (hazard ratio [HR], 1.43; 95% CI, 1.23-1.67; P < .001). When stratified by type of axillary surgery, 5-year lymphedema risk was 6.8% in whites undergoing SLNB (HR, 1 [reference]), 8.8% in blacks undergoing SLNB (HR, 1.28; 95% CI, 1.02-1.60; P = .03), 12.2% in whites undergoing ALND (1.79; 1.63-1.96; P < .001), and 18.0% in blacks undergoing ALND (2.76; 2.25-3.39; P < .001).Conclusions and relevanceAlthough SLNB use increased in both black and white patients with pathologically node-negative breast cancer from 2002 through 2007, the rates of SLNB remained lower in black than white patients during this entire period by approximately 12 percentage points. This racial disparity in SLNB use contributed to racial disparities in lymphedema risk. Improvements in the dissemination of new techniques are needed to avoid disparities in breast cancer care and patient outcomes, particularly in disadvantaged groups.
| S-EPMC5853102 | biostudies-literature