Implications of Statin Use on Vasopressor Therapy in the Setting of Septic Shock.

Background: Pleiotropic anti-inflammatory and immunomodulatory effects of statins have been associated with improved outcomes in the critically ill population. Objective: To evaluate the implications of prior statin use on the duration of vasopressor therapy in the setting of septic shock. Methods: This was a retrospective, multicenter study of adult patients who were diagnosed with septic shock. Patients were included if they were treated with any vasopressor for greater than 6 hours from the time of admission. The primary outcome was to compare the duration of vasopressor therapy in patients with septic shock with and without previous statin exposure. Results: A total of 88 statin-exposed cases and 205 unexposed controls were included in the analysis. Despite 92% of statin-exposed patients being reinitiated on therapy within 24 hours, the duration of vasopressors did not differ between groups (44 hours, statin group vs 53 hours, control group, P = .51). There were also no mortality differences between the statin group and the controls (40% vs 47%, P = .27). Conclusions: Long-term statin exposure does not impact the duration of vasopressor therapy in septic shock. The lack of differences in clinical outcomes supports the concept that sepsis involves pro- and anti-inflammatory pathways as well as other nonimmunologic pathways. Results lend further credence to the recent conceptualization of sepsis, with complications leading to organ dysfunction caused not primarily due to inflammatory responses but by a dysregulated response to infection.

Obesity, ethnicity, and quality of life among breast cancer survivors and women without breast cancer: the long-term quality of life follow-up study.

PURPOSE: The purpose of this study was to examine the relationship between obesity and quality of life (QOL) among Hispanic and non-Hispanic white breast cancer survivors and population-based controls from the 'Long-Term Quality of Life Study'--a 12- to 15-year follow-up study of breast cancer cases/survivors and controls from New Mexico (n = 451). METHODS: Using multiple linear regressions, obesity measures [body mass index (BMI) ≥ 30 kg/m(2)] at baseline and follow-up interview were modeled with composite scores for physical and mental health from the SF-36 Quality of Life Survey. Interaction between ethnicity and BMI and change in BMI were evaluated. All models were adjusted for age, ethnicity, Charlson Index, depression, fatigue, and physical activity. RESULTS: Baseline obesity (ß = -6.58, p = 0.04) was significantly associated with decreased mental health among survivors, but not among controls. Obesity at baseline and follow-up were significantly associated with decreased physical health among survivors (baseline ß = -10.51, p = 0.004; follow-up ß = -7.16, p = 0.02) and controls (baseline ß = -11.07, p < 0.001; follow-up ß = -5.18, p = 0.04). No significant interactions between ethnicity and BMI were observed. CONCLUSIONS: Our findings provide unique information about a diverse population of breast cancer survivors and controls and the impact of obesity on the mental and physical aspects of QOL.

Simeprevir and sofosbuvir with or without ribavirin to treat recurrent genotype 1 hepatitis C virus infection after orthotopic liver transplantation.

Although combination simeprevir (SIM) plus sofosbuvir (SOF) is an approved regimen for genotype 1 chronic hepatitis C virus (HCV), data regarding its safety and efficacy in liver transplant recipients remain limited. A multicenter retrospective study was performed to determine the efficacy and tolerability of a 12-week regimen of SIM/SOF with or without ribavirin (RBV) in 56 consecutive liver transplant recipients in 2014; 79% of patients had genotype 1a, 14% had cirrhosis, and 73% were treatment experienced. Sustained virological response at 12 weeks (SVR12) was 88% by intention to treat analysis (95% confidence interval, 84%-90%). Four patients relapsed, but no on-treatment virological failures occurred. The Q80K polymorphism did not impact SVR12, but there was a trend toward decreased sustained virological response with advanced fibrosis (P = 0.18). HCV RNA was detectable at treatment week 4 in 21% of patients, and those who had detectable levels were less likely to achieve SVR12 (58% versus 95%; P = 0.003). Five patients had baseline Child-Pugh class B cirrhosis, and 2 of them died (1 following early discontinuation of therapy). An additional discontinuation resulted from a severe photosensitivity reaction in a patient on concomitant cyclosporine. Seven patients receiving RBV developed progressive anemia requiring intervention. Immunosuppression dose modifications were minimal. SIM/SOF for 12 weeks was effective and well tolerated by compensated liver transplant recipients especially when administered without concomitant RBV or cyclosporine. SIM/SOF appears to have a niche as the only 12-week RBV-free treatment regimen currently recommended by guidelines for compensated transplant recipients. However, 12 weeks may not be the optimal duration of therapy for those with detectable virus at week 4 or possibly for those with cirrhosis. These data require confirmation by prospective randomized clinical trials. Liver Transplantation 22 635-643 2016 AASLD.

Associations between ALOX, COX, and CRP polymorphisms and breast cancer among Hispanic and non-Hispanic white women: The breast cancer health disparities study.

Chronic inflammation is suggested to be associated with specific cancer sites, including breast cancer. Recent research has focused on the roles of genes involved in the leukotriene/lipoxygenase and prostaglandin/cyclooxygenase pathways in breast cancer etiology. We hypothesized that genes in ALOX/COX pathways and CRP polymorphisms would be associated with breast cancer risk and mortality in our sample of Hispanic/Native American (NA) (1430 cases, 1599 controls) and non-Hispanic white (NHW) (2093 cases, 2610 controls) women. A total of 104 Ancestral Informative Markers was used to distinguish European and NA ancestry. The adaptive rank truncated product (ARTP) method was used to determine the significance of associations for each gene and the inflammation pathway with breast cancer risk and by NA ancestry. Overall, the pathway was associated with breast cancer risk (PARTP = 0.01). Two-way interactions with NA ancestry (P(adj) < 0.05) were observed for ALOX12 (rs2292350, rs2271316) and PTGS1 (rs10306194). We observed increases in breast cancer risk in stratified analyses by tertiles of polyunsaturated fat intake for ALOX12 polymorphisms; the largest increase in risk was among women in the highest tertile with ALOX12 rs9904779CC (Odds Ratio (OR), 1.49; 95% Confidence Interval (CI) 1.14-1.94, P(adj) = 0.01). In a sub-analysis stratified by NSAIDs use, two-way interactions with NSAIDs use were found for ALOX12 rs9904779 (P(adj) = 0.02), rs434473 (P(adj ) = 0.02), and rs1126667 (P(adj) = 0.01); ORs for ALOX12 polymorphisms ranged from 1.55 to 1.64 among regular users. Associations were not observed with breast cancer mortality. These findings could support advances in the discovery of new pathways related to inflammation for breast cancer treatment.

Associations between CYP19A1 polymorphisms, Native American ancestry, and breast cancer risk and mortality: the Breast Cancer Health Disparities Study.

The cytochrome p450 family 19 gene (CYP19A1) encodes for aromatase, which catalyzes the final step in estrogen biosynthesis and conversion of androgens to estrogens. Genetic variation in CYP19A1 is linked to higher circulating estrogen levels and increased aromatase expression. Using data from the Breast Cancer Health Disparities Study, a consortium of three population-based case-control studies in the United States (n = 3,030 non-Hispanic Whites; n = 2,893 Hispanic/Native Americans (H/NA) and Mexico (n = 1,810), we examined influence of 25 CYP19A1 tagging single-nucleotide polymorphisms (SNPs) on breast cancer risk and mortality, considering NA ancestry. Odds ratios (ORs) and 95 % confidence intervals (CIs) and hazard ratios estimated breast cancer risk and mortality. After multiple comparison adjustment, none of the SNPs were significantly associated with breast cancer risk or mortality. Two SNPs remained significantly associated with increased breast cancer risk in women of moderate to high NA ancestry (≥29 %): rs700518, ORGG 1.36, 95 % CI 1.11-1.67 and rs11856927, ORGG 1.35, 95 % CI 1.05-1.72. A significant interaction was observed for rs2470144 and menopausal status (p adj = 0.03); risk was increased in postmenopausal (ORAA 1.22, 95 % CI 1.05-1.14), but not premenopausal (ORAA 0.78, 95 % CI 0.64-0.95) women. The absence of an overall association with CYP19A1 and breast cancer risk is similar to previous literature. However, this analysis provides support that variation in CYP19A1 may influence breast cancer risk differently in women with moderate to high NA ancestry. Additional research is warranted to investigate the how variation in an estrogen-regulating gene contributes to racial/ethnic disparities in breast cancer.

Associations between genetic variants in the TGF-ß signaling pathway and breast cancer risk among Hispanic and non-Hispanic white women.

The TGF-ß signaling pathway has a significant role in breast cancer initiation and promotion by regulating various cellular processes. We evaluated whether genetic variation in eight genes (TGF-ß1, TGF-ß2, TGF-ßR1, TGF-ßR2, TGF-ßR3, RUNX1, RUNX2, and RUNX3) is associated with breast cancer risk in women from the Breast Cancer Health Disparities Study. A total of 3,524 cases (1,431 non-Hispanic whites (NHW); 2,093 Hispanics/Native Americans(NA)) and 4,209 population-based controls (1,599 NHWs; 2,610 Hispanics/NAs) were included in analyses. Genotypes for 47 single nucleotide polymorphisms (SNPs) were determined. Additionally, 104 ancestral informative markers estimated proportion of NA ancestry. Associations with breast cancer risk overall, by menopausal status, NA ancestry, and estrogen receptor (ER)/progesterone receptor tumor phenotype were evaluated. After adjustment for multiple comparisons, two SNPs were significantly associated with breast cancer risk: RUNX3 (rs906296 ORCG/GG = 1.15 95 % CI 1.04-1.26) and TGF-ß1 (rs4803455 ORCA/AA = 0.89 95 % CI 0.81-0.98). RUNX3 (rs906296) and TGF-ßR2 (rs3773644) were associated with risk in pre-menopausal women (p adj = 0.002 and 0.02, respectively) and in those with intermediate to high NA ancestry (p adj = 0.04 and 0.01, respectively). Self-reported race was strongly correlated with NA ancestry (r = 0.86). There was a significant interaction between NA ancestry and RUNX1 (rs7279383, p adj = 0.04). Four RUNX SNPs were associated with increased risk of ER- tumors. Results provide evidence that genetic variation in TGF-ß and RUNX genes are associated with breast cancer risk. This is the first report of significant associations between genetic variants in TGF-ß and RUNX genes and breast cancer risk among women of NA ancestry.

Sex hormone changes during weight loss and maintenance in overweight and obese postmenopausal African-American and non-African-American women.

INTRODUCTION: Changes in sex hormones with weight loss might have implications for breast cancer prevention but have not been examined extensively, particularly in African-American (AA) women. METHODS: We conducted a prospective study of 278 overweight/obese postmenopausal women (38% AA) not taking hormone therapy within the Weight Loss Maintenance Trial. All participants lost at least 4 kg after a 6-month weight-loss phase and attempted to maintain weight loss during the subsequent 12 months. We evaluated the percentage changes in estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) using generalized estimating equations. RESULTS: In all study phases, AA women had higher levels of estrogen and testosterone concentrations, independent of adiposity. On average, participants lost 7.7 kg during the weight-loss phase, and concentrations of estrone (-5.7%, P = 0.006), estradiol (-9.9%, P <0.001), free estradiol (-13.4%, P <0.0001), and free testosterone (-9.9%, P <0.0001) decreased, while the SHBG concentration (16.2%, P <0.001) increased. Weight change did not significantly affect total testosterone or other androgen concentrations. Compared with non-AA women, AA women experienced less change in estrogens per kilogram of weight change (that is, per 1 kg weight loss: estrone, -0.6% vs. -1.2%, P-interaction = 0.10; estradiol, -1.1% vs. -1.9%, P-interaction = 0.04; SHBG, 0.9% vs. 1.6%, P-interaction = 0.006; free estradiol, -1.4% vs. -2.1%, P-interaction = 0.01). CONCLUSION: To the best of our knowledge this is the first study to examine and compare the effects of intentional weight loss and maintenance on a panel of sex hormones in AA women and non-AA women. Although speculative, these data suggest hormonal differences may contribute to different racial patterns of breast cancer incidence and mortality and encourage further investigations to understand the long-term effects of weight loss on sex hormones in obese postmenopausal women. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00054925.

Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Survey.

BACKGROUND: Polychlorinated biphenyl (PCB) exposures have been associated with liver injury in human cohorts, and steatohepatitis with liver necrosis in model systems. MicroRNAs (miRs) maintain cellular homeostasis and may regulate the response to environmental stress. OBJECTIVES: We tested the hypothesis that specific miRs are associated with liver disease and PCB exposures in a residential cohort. METHODS: Sixty-eight targeted hepatotoxicity miRs were measured in archived serum from 734 PCB-exposed participants in the cross-sectional Anniston Community Health Survey. Necrotic and other liver disease categories were defined by serum keratin 18 (K18) biomarkers. Associations were determined between exposure biomarkers (35 ortho-substituted PCB congeners) and disease biomarkers (highly expressed miRs or previously measured cytokines), and Ingenuity Pathway Analysis was performed. RESULTS: The necrotic liver disease category was associated with four up-regulated miRs (miR-99a-5p, miR-122-5p, miR-192-5p, and miR-320a) and five down-regulated miRs (let-7d-5p, miR-17-5p, miR-24-3p, miR-197-3p, and miR-221-3p). Twenty-two miRs were associated with the other liver disease category or with K18 measurements. Eleven miRs were associated with 24 PCBs, most commonly congeners with anti-estrogenic activities. Most of the exposure-associated miRs were associated with at least one serum hepatocyte death, pro-inflammatory cytokine or insulin resistance bioarker, or with both. Within each biomarker category, associations were strongest for the liver-specific miR-122-5p. Pathways of liver toxicity that were identified included inflammation/hepatitis, hyperplasia/hyperproliferation, cirrhosis, and hepatocellular carcinoma. Tumor protein p53 and tumor necrosis factor α were well integrated within the top identified networks. DISCUSSION: These results support the human hepatotoxicity of environmental PCB exposures while elucidating potential modes of PCB action. The MiR-derived liquid liver biopsy represents a promising new technique for environmental hepatology cohort studies. https://doi.org/10.1289/EHP9467.

Serotonin-Modulating Antidepressants and Risk of Bleeding after Trauma.

Serotonin-modulating antidepressants have been associated with increased risk of gastrointestinal bleeding and increased blood loss during elective surgery. This study sought to investigate the effect of preinjury selective-serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) use on transfusion requirements after trauma, and to evaluate whether resumption of SSRI/SNRI after trauma may worsen bleeding risk. This was a retrospective matched-cohort study evaluating patients with solid organ injury. Preinjury SSRI/SNRI users were matched to non-SSRI/SNRI users based on age, preinjury aspirin use, Injury Severity Score, and abdominal Abbreviated Injury Severity Score. The primary endpoint was transfusion requirement during hospitalization. The absolute need for transfusion was higher in SSRI/SNRI users throughout hospitalization (50.9% vs 37.3%, P = 0.02). After logistic multivariate analysis, SSRI/SNRI users were more likely to require transfusion at 24 hours (odds ratio (95% confidence interval): 2.73 (1.41, 5.29), P = 0.003), but this difference did not persist for overall hospitalization (odds ratio (95% confidence interval): 1.32 (0.74, 2.36), P = 0.35). Fewer patients restarted on SSRI/SNRI therapy within 72 hours required packed red blood cell transfusion compared with those who were restarted later or not at all (43.2% vs 60.3%; P = 0.04). Preinjury use of serotonin-modulating antidepressants led to an increased requirement of blood transfusions after solid organ injury. Although clinicians should weigh bleeding risk before reinitiation of SSRI/SNRI, the results of this study indicate that reasonable efforts to restart these medications after stabilization do not result in further risk for transfusion.

Liver Disease in a Residential Cohort With Elevated Polychlorinated Biphenyl Exposures.

Endocrine and metabolism disrupting chemicals (EDCs/MDCs) have been associated with environmental liver diseases including toxicant-associated steatohepatitis (TASH). TASH has previously been characterized by hepatocellular necrosis, disrupted intermediary metabolism, and liver inflammation. Polychlorinated biphenyls (PCBs) are environmental EDCs/MDCs associated with the genesis and progression of steatohepatitis in animal models and human liver injury in epidemiology studies. The cross-sectional Anniston Community Health Survey (ACHS) investigates ortho-substituted PCB exposures and health effects near a former PCB manufacturing complex. The rates of obesity, diabetes, and dyslipidemia were previously determined to be high in ACHS. In this study, 738 ACHS participants were categorized by liver disease status using the serum cytokeratin 18 biomarker. Associations between PCB exposures and mechanistic biomarkers of intermediary metabolism, inflammation, and hepatocyte death were determined. The liver disease prevalence was high (60.2%), and 80.7% of these individuals were categorized as having TASH. Sex and race/ethnicity differences were noted. TASH was associated with increased exposures to specific PCB congeners, insulin resistance, dyslipidemia, proinflammatory cytokines, and liver necrosis. These findings are consistent with PCB-related steatohepatitis. ΣPCBs was inversely associated with insulin resistance/production, leptin, and hepatocyte apoptosis, while other adipocytokines were increased. This is possibly the largest environmental liver disease study applying mechanistic biomarkers ever performed and the most comprehensive analysis of PCBs and adipocytokines. It provides insight into the mechanisms of PCB-related endocrine and metabolic disruption in liver disease and diabetes. In the future, associations between additional exposures and liver disease biomarkers will be evaluated in the ACHS and follow-up ACHS-II studies.

Surgical Wound Classification and Surgical Site Infections in the Orthopaedic Patient.

INTRODUCTION: The Centers for Disease Control and Prevention created a surgical wound classification system (SWC: I, clean; II, clean/contaminated; III, contaminated; and IV, dirty) to preemptively identify patients at risk of surgical site infection (SSI). The validity of this system is yet to be demonstrated in orthopaedic surgery. We hypothesize a poor association between the SWC and the rate of subsequent SSI in orthopaedic trauma cases. METHODS: Nine hundred fifty-six orthopaedic cases were reviewed. Wounds were risk stratified intraoperatively using the SWC grades (I-IV). SSI was diagnosed clinically or with objective markers. The SWC was compared with SSI rates using a Fisher exact test. Significance was set at P < 0.05. RESULTS: Four hundred patients met the selection criteria. The rate of infection was not significantly different across the SWC grades (P = 0.270). There was a significantly higher risk of SSI among patients with diabetes (P = 0.028). CONCLUSIONS: The Centers for Disease Control and Prevention SWC showed poor utility in predicting and risk stratifying postoperative SSIs in orthopaedic surgical cases.

Associations between prior HPV4 vaccine doses and cervical cancer screening participation.

BACKGROUND: Cervical cancer screening, regardless of HPV vaccination, is a cornerstone of cancer prevention. This study evaluated associations between prior HPV vaccine doses and initiation and continued participation of screening by age at vaccination. METHODS: Using electronic medical records for a safety net healthcare system (Truman Medical Center), women aged 14-26y vaccinated (n=1123) between 07/01/2006 and 10/1/2009 were randomly selected and matched on birth year and health campus to unvaccinated (n=1123) women. Frequency of screening was determined through 07/01/2013. Hazard ratios (HR) for screening were estimated using Cox proportional hazards regression. RESULTS: Screening rates were higher after vaccination: unvaccinated (53%), first (62%), second (59%) or third (61%) doses. Women who initiated screening were less likely to complete the vaccine series, regardless of age. Women receiving one dose were more likely than unvaccinated women to initiate screening (HR=2.98 95% Confidence Interval (CI):2.45-3.61) and were more likely to screen than those receiving two (1 vs. 2, HR=2.94 95% CI:2.09-4.14) or three doses (1 vs. 3, HR=3.15 95% CI:2.21-4.48). Compared to unvaccinated women, women <21y who completed 3-doses were 1.8-times more likely to screen at ≥21y, whereas vaccinated women ≥21y were more likely to screen regardless of number of doses (p<0.0001). CONCLUSIONS: Women who were vaccinated were more likely to screen than unvaccinated women; screening rate was highest after and occurred closest to the first vaccine dose. Research evaluating the efficacy of a one-dose vaccine is warranted and may provide both higher vaccination and screening rates.

Cigarette Smoking and Breast Cancer Risk in Hispanic and Non-Hispanic White Women: The Breast Cancer Health Disparities Study.

OBJECTIVE: Few epidemiological studies have included Hispanics with the evaluation of the effects of cigarette smoking and breast cancer. We examined the relationship between cigarette smoking, ethnicity, and breast cancer risk using data from the Breast Cancer Health Disparities Study (BCHDS). MATERIALS AND METHODS: The BCHDS is a consortium of three population-based case-control studies, including U.S. non-Hispanic whites (NHWs) (1,525 cases; 1,593 controls), U.S. Hispanics/Native Americans (1,265 cases; 1,495 controls), and Mexican women (990 cases; 1,049 controls). Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Breast cancer risk was elevated among Mexican former smokers (OR 1.43, 95% CI 1.04-1.96) and among those who smoked ≥ 31 years (OR 1.95, 95% CI 1.13-3.35), compared to never smokers. In addition, Mexican former smokers with a history of alcohol consumption had increased breast cancer risk (OR 2.30, 95% CI 1.01-5.21). Among NHW premenopausal women, breast cancer risk was increased for smoking ≥ 20 cigarettes per day (OR 1.61, 95% CI 1.07-2.41). CONCLUSION: Our findings suggest the possibility of ethnic differences with the associations between cigarette smoking and breast cancer risk.

Physical activity and survival among Hispanic and non-Hispanic white long-term breast cancer survivors and population-based controls.

PURPOSE: We investigated the association of physical activity with survival for 601 Hispanic women and 682 non-Hispanic white women who participated in the population-based breast cancer case-control New Mexico Women's Health Study. METHODS: We identified 240 deaths among cases diagnosed with a first primary invasive breast cancer between 1992 and 1994, and 88 deaths among controls. Follow-up extended through 2012 for cases and 2008 for controls. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: Higher levels of total physical activity were inversely associated with all-cause mortality among Hispanic cases (Quartile (Q)4: HR = 0.55, 95% CI 0.31-0.99). A non-significant trend was observed for recreational activity in Hispanic cases also (Q4: HR = 0.50, 95% CI 0.23-1.09, p for trend = 0.08). No significant associations were noted for non-Hispanic white cases or for controls. CONCLUSIONS: The results suggest that increasing physical activity may be protective against mortality in Hispanic women with breast cancer, despite reporting lower levels of recreational activity than non-Hispanic white women or Hispanic controls. IMPLICATIONS FOR CANCER SURVIVORS: Public health programs in Hispanic communities should promote physical activity in women as a means of decreasing breast cancer risk and improving survival.

Treatment-related risk factors for arm lymphedema among long-term breast cancer survivors.

INTRODUCTION: Treatment-related factors may increase the risk for arm lymphedema, which may occur after surgery or even many years after initial treatment for breast cancer. The association between treatment-related risk factors and development of arm lymphedema was examined for women who participated in the long-term quality of life (LTQOL) study, a 12-15-year follow-up of a breast cancer case-control study of Hispanic and non-Hispanic white women. METHODS: Among 199 cases, 43 women (15 Hispanic, 28 non-Hispanic white) reported physician-diagnosed lymphedema during follow-up. Multivariable logistic regression analysis was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the association of risk factors with lymphedema, adjusting for relevant covariates. RESULTS: Tamoxifen had a non-significant, positive association with lymphedema (OR = 2.07, 95% CI 0.94-4.55, p =0.07). There were no significant associations with type of surgery, radiation, or chemotherapy. Risk was increased specifically in overweight and obese women (body mass index (BMI) > =25 kg/m(2)) treated with tamoxifen (OR = 2.62, 95% CI 0.99-6.93, p = 0.05). CONCLUSIONS: This study suggests that breast cancer survivors with a BMI >25 who report the use of tamoxifen therapy may be at increased risk for arm lymphedema. IMPLICATIONS FOR CANCER SURVIVORS: Larger case-control studies and clinical trials should investigate the long-term association of tamoxifen treatment with arm lymphedema especially in overweight and obese women. Lymphedema risk may be another indication to consider a weight reduction program in breast cancer survivors.

Active and passive cigarette smoking and mortality among Hispanic and non-Hispanic white women diagnosed with invasive breast cancer.

PURPOSE: Women who smoke at breast cancer diagnosis have higher risk of breast cancer-specific and all-cause mortality than nonsmokers; however, differences by ethnicity or prognostic factors and risk for noncancer mortality have not been evaluated. METHODS: We examined associations of active and passive smoke exposure with mortality among Hispanic (n = 1020) and non-Hispanic white (n = 1198) women with invasive breast cancer in the Breast Cancer Health Disparities Study (median follow-up of 10.6 years). RESULTS: Risk of breast cancer-specific (HR = 1.55, 95% CI = 1.11-2.16) and all-cause (HR = 1.68, 95% CI = 1.30-2.17) mortality was increased for current smokers, with similar results stratified by ethnicity. Ever smokers had an increased risk of noncancer mortality (HR = 1.68, 95% CI = 1.12-2.51). Associations were strongest for current smokers who smoked for 20 years or more were postmenopausal, overweight and/or obese, or reported moderate and/or high alcohol consumption; however, interactions were not significant. Breast cancer-specific mortality was increased two fold for moderate and/or high recent passive smoke exposure among never smokers (HR = 2.12, 95% CI = 1.24-3.63). CONCLUSIONS: Findings support associations of active-smoking and passive-smoking diagnosis with risk of breast cancer-specific and all-cause mortality and ever smoking with noncancer mortality, regardless of ethnicity, and other factors. Smoking is a modifiable lifestyle factor and effective smoking cessation, and maintenance programs should be routinely recommended for women with breast cancer.

Epidermal growth factor receptor (EGFR) polymorphisms and breast cancer among Hispanic and non-Hispanic white women: the Breast Cancer Health Disparities Study.

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.