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Insulin resistance contributes to racial disparities in breast cancer prognosis in US women.

ABSTRACT: BACKGROUND: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 receptor (IR) and insulin-like growth factor receptor (IGF-1R) expression differs between tumors from Black and White women. METHODS:We conducted a cross-sectional, multi-center study across ten hospitals. Self-identified Black women and White women with newly diagnosed invasive breast cancer were recruited. The primary outcome was to determine if insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR), mediated the effect of race on prognosis using the multivariate linear mediation model. Demographic data, anthropometric measurements, and fasting blood were collected. Poor prognosis was defined as a Nottingham Prognostic Index (NPI) >?4.4. Breast cancer pathology specimens were evaluated for IR and IGF-1R expression by immunohistochemistry (IHC). RESULTS:Five hundred fifteen women were recruited (83% White, 17% Black). The MetS was more prevalent in Black women than in White women (40% vs 20%, p?? 1: 4.2?±?0.8 vs IR/IGF-1R?=?1: 3.9?±?0.8 vs IR/IGF-1R?

SUBMITTER: Gallagher EJ

PROVIDER: S-EPMC7216707 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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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]

PMID: 32393319

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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.

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.

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.

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.

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.

Dataset Information

Insulin resistance contributes to racial disparities in breast cancer prognosis in US women.

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Insulin resistance contributes to racial disparities in breast cancer prognosis in US women.

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