Treatment-related side effects among Hispanic and non-Hispanic white long-term breast cancer survivors by tamoxifen use and duration.

PURPOSE: To determine the associations between ethnicity, age at diagnosis, obesity, multimorbidity, and odds of experiencing breast cancer (BC) treatment-related side effects among long-term Hispanic and non-Hispanic white (NHW) survivors from New Mexico and explore differences by tamoxifen use. METHODS: Lifestyle and clinical information including self-reported tamoxifen use and presence of treatment- related side effects were collected at follow-up interviews (12-15 years) for 194 BC survivors. Multivariable logistic regression models were used to examine associations between predictors and odds of experiencing side effects overall and by tamoxifen use. RESULTS: Women ranged in age at diagnosis (30-74, M = 49.3, SD = 9.37), most were NHW (65.4%) and had in-situ or localized BC (63.4%). Less than half reportedly used tamoxifen (44.3%), of which 59.3% reported using > 5 years. Overall, survivors who were overweight/obese at follow-up were 5.42 times more likely to experience treatment-related pain (95% CI 1.40-21.0) compared to normal weight survivors. Survivors with multimorbidity, compared to survivors without, were more likely to report treatment-related sexual health issues (aOR 6.90, 95% CI 1.43-33.2) and poorer mental health (aOR 4.51, 95% CI 1.06-19.1). The statistical interactions between ethnicity and overweight/obese with tamoxifen use were significant (p-interaction < 0.05) for treatment-related sexual health issues. CONCLUSION: Our results demonstrate that survivors with overweightness/obesity or multimorbidity may be more likely to experience BC treatment-related side effects. Tamoxifen use modifies associations between ethnicity, being overweight/obese, and sexual health issues following treatment. The likelihood of experiencing treatment-related side effects were more favorable for those on tamoxifen or those who had used tamoxifen for longer durations. These findings highlight the importance of fostering side effect awareness and applying appropriate interventions to assist with disease management throughout BC survivorship care.

Systemic inflammation and risk of all-cause mortality after invasive breast cancer diagnosis among Hispanic and non-Hispanic white women from New Mexico.

INTRODUCTION: Soluble tumor necrosis factor receptor-II (sTNF-R2), a pro-inflammatory biomarker, is associated with obesity and breast cancer (BC). The association between sTNF-R2 and risk of mortality after BC has not been studied, specifically among Hispanic women, an at-risk population due to their high prevalence of obesity and poor prognosis. We examined the association between sTNF-R2 and mortality among Hispanic and non-Hispanic white (NHW) BC survivors. METHODS: A total of 397 invasive BC survivors (96 Hispanic, 301 NHW) contributed baseline interview data and blood samples. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression models adjusting for clinical factors including body mass index. RESULTS: After a median follow-up time of 13 years, 133 deaths occurred. The association between high vs low levels of plasma sTNF-R2 and mortality was not statistically significant overall (HR, 1.32; 95% CI 0.89-1.98). However, when stratified the mortality risk among Hispanic women was nearly 3-fold (HR, 2.83; 95% CI 1.21-6.63), while risk among NHW women was attenuated (HR, 0.99; 95% CI 0.61-1.61) (p-interaction=0.10). CONCLUSION: Our results suggest Hispanic BC survivors with high sTNF-R2 levels may have increased risk of mortality and could inform targeted interventions to reduce inflammation and improve outcomes.

Self-reported symptoms of arm lymphedema and health-related quality of life among female breast cancer survivors.

We examined cross-sectional associations between arm lymphedema symptoms and health-related quality of life (HRQoL) in the Health, Eating, Activity and Lifestyle (HEAL) Study. 499 women diagnosed with localized or regional breast cancer at ages 35-64 years completed a survey, on average 40 months after diagnosis, querying presence of lymphedema, nine lymphedema-related symptoms, e.g., tension, burning pain, mobility loss, and warmth/redness, and HRQoL. Analysis of covariance models were used to assess HRQoL scores in relation to presence of lymphedema and lymphedema-related symptoms. Lymphedema was self-reported by 137 women, of whom 98 were experiencing lymphedema at the time of the assessment. The most common symptoms were heaviness (52%), numbness (47%), and tightness (45%). Perceived physical health was worse for women reporting past or current lymphedema than those reporting no lymphedema (P-value < 0.0001). No difference was observed for perceived mental health (P-value = 0.31). Perceived physical health, stress, and lymphedema-specific HRQoL scores worsened as number of symptoms increased (P-values ≤ 0.01). Women reporting tension in the arm had lower physical health (P-value = 0.01), and those experiencing burning pain, tension, heaviness, or warmth/redness in the arm had lower lymphedema-specific HRQoL (P-values < 0.05). Treatment targeting specific lymphedema-related symptoms in addition to size/volume reduction may improve some aspects of HRQoL among affected women.

Physical activity, ethnicity, and quality of life among breast cancer survivors and population-based controls: the long-term quality of life follow-up study.

PURPOSE: To explore the relationship between physical activity (PA) and quality of life (QOL) among Hispanic and non-Hispanic white breast cancer (BC) cases and population-based controls from the New Mexico 'Long-Term Quality of Life Study'. METHODS: Self-reported PA (low, moderate, vigorous MET hours/week) at baseline and follow-up interviews (12-15 years) were available for 391 cases and controls and modeled using multiple linear regressions with SF-36 mean composite scores for physical and mental health. The change in PA from baseline to follow-up and interactions with ethnicity were also examined. Models were adjusted for age at diagnosis/baseline interview, education, comorbidities, body mass index, and change in PA. RESULTS: PA intensities at each timepoint did not differ by case/control status; however, the change in vigorous PA was lower among cases (p = 0.03). At follow-up, low intensity PA increased mental health QOL scores among cases; however, the interaction between low intensity PA and ethnicity was statistically significant among controls indicating decreased mental health among Hispanics (p = 0.02). Change in moderate PA was associated with increased physical and mental health among cases (physical: ß = 0.186, p = 0.008; mental: ß = 0.225, p = 0.001) and controls (physical: ß = 0.220, p < 0.0001; mental: ß = 0.193, p = 0.002), when controlling for confounders. CONCLUSION: Our results demonstrate that all levels of PA are important for mental health among BC cases, while activities of higher intensity are important for physical health among women overall. The statistical interaction observed between ethnicity and low intensity PA among controls for mental health warrants further research to provide a meaningful interpretation.

Ethnic and biological differences in the association between physical activity and survival after breast cancer.

Physical activity is recommended for most cancer patients as a nonpharmacological therapy to improve prognosis. Few studies have investigated the association between physical activity and breast cancer prognosis by ethnicity, biological, and modifiable risk factors for mortality. We investigated the association between physical activity and long-term survival among breast cancer survivors. A total of 397 survivors (96 Hispanic and 301 non-Hispanic White (NHW)) from the New Mexico HEAL study contributed baseline and biological data approximately 6 months after diagnosis. Study outcomes included all-cause, breast cancer-specific, and non-breast cancer mortality. The exposure was self-reported physical activity within the past month. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox Proportional Hazards regression. A total of 133 deaths (53 breast cancer-specific deaths) were observed after a median follow-up time of 13 years. Engaging in >6.9 metabolic equivalent hours/week (MET-h/week) of moderate to vigorous physical activity (active) was inversely associated with all-cause mortality among all women (HR 0.66, 95% CI 0.43-0.99) and NHWs (HR 0.58, 95% CI 0.36-0.94). Active NHW women also had a reduced risk of non-breast cancer mortality (HR 0.56, 95% CI 0.31-0.99), compared to inactive women (0 MET-h/week). In subgroups, we observed the inverse associations with all-cause mortality among women >58 years old (p-interaction= 0.03) and with localized stage (p-interaction = 0.046). Our results confirm the protective association between physical activity and mortality after breast cancer diagnosis, and demonstrate that this association significantly differs by age and cancer stage. Larger studies are warranted to substantiate our findings.

Bayesian credible subgroup identification for treatment effectiveness in time-to-event data.

Due to differential treatment responses of patients to pharmacotherapy, drug development and practice in medicine are concerned with personalized medicine, which includes identifying subgroups of population that exhibit differential treatment effect. For time-to-event data, available methods only focus on detecting and testing treatment-by-covariate interactions and may not consider multiplicity. In this work, we introduce the Bayesian credible subgroups approach for time-to-event endpoints. It provides two bounding subgroups for the true benefiting subgroup: one which is likely to be contained by the benefiting subgroup and one which is likely to contain the benefiting subgroup. A personalized treatment effect is estimated by two common measures of survival time: the hazard ratio and restricted mean survival time. We apply the method to identify benefiting subgroups in a case study of prostate carcinoma patients and a simulated large clinical dataset.

Pyoderma Gangrenosum in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon but severe extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD). The incidence and risk factors for PG are disputed. AIMS: To assess the incidence of PG and identify factors associated with PG in IBD patients. METHODS: A search of electronic databases (Ovid and PubMed) was conducted between 1966 and 2019. Studies that calculated the incidence of PG in IBD patient cohorts were included. Patient demographics, IBD subtype, and EIM presence were recorded. A review of our institutional database of 1057 IBD patients was conducted. A multivariate regression model and meta-analysis were conducted to identify risk factors for PG. A random effects model was used to combine the data of included studies. RESULTS: Fourteen studies were included in addition to 1057 IBD patients and 26 PG cases from the Louisville cohort. In total, there were 379 cases of PG in the cumulative cohort of 61,695 IBD patients. The PG incidence in individual studies ranged from 0.4 to 2.6%. In the institutional cohort, ocular EIMs and a permanent stoma were significant risk factors for PG. In the meta-analysis, PG was associated with female gender (RR = 1.328, 95% CI 1.161-1.520), Crohn's disease (RR = 1.193, 95% CI 1.001-1.422), erythema nodosum (RR = 9.281, 95% CI 6.081-14.164), and ocular EIM (RR = 4.55, 95% CI 3.04-6.81). There was study heterogeneity when assessing IBD subtype, ocular, and joint EIMs. CONCLUSIONS: There are conflicting data on the incidence and risk factors for PG. This meta-analysis confirms an association between PG and female gender, Crohn's disease, erythema nodosum, and ocular EIM that have been described in smaller studies.

Fructosamine and diabetes as predictors of mortality among Hispanic and non-Hispanic white breast cancer survivors.

Epidemiologic studies have found that elevated insulin levels and chronic hyperglycemia among breast cancer (BC) survivors are associated with poor prognosis; few of these studies have included Hispanic women in whom diabetes is highly prevalent. We examined the associations between circulating fructosamine-a biomarker of hyperglycemia and blood glucose control, self-reported diabetes, and risk of BC-specific and all-cause mortality among Hispanic and non-Hispanic white (NHW) women diagnosed with invasive BC. A total of 399 BC survivors (96 Hispanic, 303 NHW) contributed baseline data and plasma samples. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable Cox proportional hazards regression models. After a median follow-up time of 13 years, a total of 134 deaths occurred, of which 56 deaths were from BC. Diabetes was associated with BC-specific (HR, 2.89; 95% CI 1.27-6.60) and all-cause (HR, 2.10; 95% CI 1.24-3.55) mortality. Associations were stronger among women with clinically high fructosamine levels (>285 µmol/L) (BC-specific: HR, 4.25; 95% CI 1.67-10.80; all-cause: HR, 2.32; 95% CI 1.30-4.14) compared to women with normal levels (≤285 µmol/L). In mediation analysis, fructosamine explained 47% of the association between diabetes and all-cause mortality and 41% of BC-specific mortality; the largest attenuation was among Hispanics for all-cause mortality (56%). Our results demonstrate that poor glycemic control explains a large extent of the relationship between diabetes and mortality among women with invasive BC, particularly among Hispanic women. The associations we observed for BC mortality should be confirmed in larger studies of ethnically diverse BC patients.

Healthy lifestyle impact on breast cancer-specific and all-cause mortality.

PURPOSE: While several studies have evaluated the association of combined lifestyle factors on breast cancer-specific mortality, few have included Hispanic women. We constructed a "healthy behavior index" (HBI) and evaluated its associations with mortality in non-Hispanic White (NHW) and Hispanic women diagnosed with breast cancer from the southwestern U.S. METHODS: Diet and lifestyle questionnaires were analyzed for 837 women diagnosed with invasive breast cancer (1999-2004) in New Mexico as part of the 4-Corners Women's Health Study. An HBI score ranging from 0 to 12 was based on dietary pattern, physical activity, smoking, alcohol consumption, and body size and shape, with increasing scores representing less healthy characteristics. Hazard ratios for mortality over 14 years of follow-up were estimated for HBI quartiles using Cox proportional hazards models adjusting for education and stratified by ethnicity and stage at diagnosis. RESULTS: A significant increasing trend was observed across HBI quartiles among all women, NHW women, and those diagnosed with localized or regional/distant stage of disease for all-cause (AC) mortality (p-trend = 0.006, 0.002, 0.03, respectively). AC mortality was increased >2-fold for all women and NHW women in HBI Q4 versus Q1 (HR = 2.18, 2.65, respectively). The association was stronger in women with regional/distant than localized stage of disease (HR = 2.62, 1.94, respectively). Associations for Hispanics or breast cancer-specific mortality were not significant. CONCLUSIONS: These findings indicate the associations between the HBI and AC mortality, which appear to differ by ethnicity and stage at diagnosis. Interventions for breast cancer survivors should address the combination of lifestyle factors on prognosis.

Genetic variation in TNFα, PPARγ, and IRS-1 genes, and their association with breast-cancer survival in the HEAL cohort.

PURPOSE: Tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPARγ), and insulin receptor substrate-1 (IRS-1) are associated with obesity, insulin resistance, and inflammation. Few data exist on associations between polymorphisms in these genes and mortality in breast cancer survivors. METHODS: We investigated associations between TNF-α -308G > A (rs1800629); PPARγ Pro12Ala (rs1801282); and IRS-1 Gly972Arg (rs1801278) polymorphisms and anthropometric variables, circulating levels of previously measured biomarkers, and tumor characteristics in 553 women enrolled in the Health, Eating, Activity, and Lifestyle Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer between 1995 and 1999 (median follow-up 14.7 years).  Using Cox proportional hazards models adjusted for possible confounders, we evaluated associations between these polymorphisms and mortality. RESULTS: Carriers of the PPARγ variant allele had statistically significantly lower rates of type 2 diabetes (P = 0.04), lower BMI (P = 0.01), and HOMA scores [P = 0.004; non-Hispanic White (NHWs) only]; carriers of the TNF-α variant A allele had higher serum glucose (P = 0.004, NHW only); and the IRS-1 variant was associated with higher leptin levels (P = 0.003, Hispanics only). There were no associations between any of the polymorphisms and tumor characteristics. Among 141 deaths, 62 were due to breast cancer. Carriers of the TNF-α-variant A allele had a decreased risk of breast-cancer-specific mortality [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.10-0.83] and all-cause mortality (HR 0.51; 95% CI 0.28-0.91). CONCLUSIONS: Neither the PPARγ nor the IRS-1 polymorphism was associated with mortality outcome. The TNF-α -308 G > A polymorphism was associated with reduced breast-cancer-specific and all-cause mortality.

Associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white women diagnosed with breast cancer: the Breast Cancer Health Disparities Study.

PURPOSE: ALDH1A1, one of the main isotopes of aldehyde dehydrogenase-1 is involved in the differentiation and protection of normal hematopoietic stem cells and functions in alcohol sensitivity and dependence. We evaluated the associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white (NHW) breast cancer (BC) cases from the Breast Cancer Health Disparities Study. METHODS: Nine SNPs in ALDH1A1 were evaluated in 920 Hispanic and 1372 NHW women diagnosed with incident invasive BC. Adjusted Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were stratified by Native American (NA) ancestry and alcohol consumption. RESULTS: A total of 443 deaths occurred over a median follow-up time of 11 years. After adjusting all results for multiple comparisons, rs7027604 was significantly associated with all-cause mortality (HRAA = 1.40; 95% CI 1.13-1.73, P adj = 0.018). The rs1424482 CC genotype (HRCC = 1.69; 95% CI 1.20-2.37, P adj = 0.027) and the rs7027604 AA genotype (HRAA = 1.65; 95% CI 1.21-2.26, P adj = 0.018) were positively associated with non-BC mortality. Among long-term light drinkers, rs1888202 was associated with decreased all-cause mortality (HRCG/GG = 0.36; 95% CI 0.20-0.64), while associations were not significant among non-drinkers or moderate/heavy drinkers (P interation = 0.218). The increased risk of all-cause mortality associated with rs63319 was limited to women with low NA ancestry (HRAA = 1.53; 95% CI 1.19-1.97). CONCLUSIONS: Multiple SNPs in ALDH1A1 were associated with increased risk of mortality after BC. Future BC studies examining the relationship between ALDH1A1 and mortality should consider the modifying effects of alcohol consumption and NA ancestry.

A comparison of confidence/credible interval methods for the area under the ROC curve for continuous diagnostic tests with small sample size.

The receiver operating characteristic (ROC) curve is frequently used as a measure of accuracy of continuous markers in diagnostic tests. The area under the ROC curve (AUC) is arguably the most widely used summary index for the ROC curve. Although the small sample size scenario is common in medical tests, a comprehensive study of small sample size properties of various methods for the construction of the confidence/credible interval (CI) for the AUC has been by and large missing in the literature. In this paper, we describe and compare 29 non-parametric and parametric methods for the construction of the CI for the AUC when the number of available observations is small. The methods considered include not only those that have been widely adopted, but also those that have been less frequently mentioned or, to our knowledge, never applied to the AUC context. To compare different methods, we carried out a simulation study with data generated from binormal models with equal and unequal variances and from exponential models with various parameters and with equal and unequal small sample sizes. We found that the larger the true AUC value and the smaller the sample size, the larger the discrepancy among the results of different approaches. When the model is correctly specified, the parametric approaches tend to outperform the non-parametric ones. Moreover, in the non-parametric domain, we found that a method based on the Mann-Whitney statistic is in general superior to the others. We further elucidate potential issues and provide possible solutions to along with general guidance on the CI construction for the AUC when the sample size is small. Finally, we illustrate the utility of different methods through real life examples.

Pre-diagnostic breastfeeding, adiposity, and mortality among parous Hispanic and non-Hispanic white women with invasive breast cancer: the Breast Cancer Health Disparities Study.

BACKGROUND: U.S. Hispanic women have high rates of parity, breastfeeding, and obesity. It is unclear whether these reproductive factors are associated with breast cancer (BC) mortality. We examined the associations between breastfeeding, parity, adiposity and BC-specific and overall mortality in Hispanic and non-Hispanic white (NHW) BC cases. METHODS: The study population included 2921 parous women (1477 Hispanics, 1444 NHWs) from the Breast Cancer Health Disparities Study with invasive BC diagnosed between 1995 and 2004. Information on reproductive history and lifestyle factors was collected by in-person interview. Overall and stratified Cox proportional hazard regression models by ethnicity, parity, and body mass index (BMI) at age 30 years were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: After a median follow-up time of 11.2 years, a total of 679 deaths occurred. Pre-diagnostic breastfeeding was associated with a 16% reduction in mortality (HR 0.84; 95% 0.72-0.99) irrespective of ethnicity. Parity significantly modified the association between breastfeeding duration and mortality (p interaction = 0.05), with longer breastfeeding duration associated with lower risk among women who had ≤2 births (p trend = 0.02). Breastfeeding duration was associated with reduced risk of both BC-specific and overall mortality among women with BMI <25 kg/m2, while positive associations were observed among women with BMI ≥25 kg/m2 (p interactions <0.01). CONCLUSION: Pre-diagnostic breastfeeding was inversely associated with risk of mortality after BC, particularly in women of low parity or normal BMI. These results provide another reason to encourage breastfeeding and weight management among young women.

Use of complementary and alternative medicine and breast cancer survival in the Health, Eating, Activity, and Lifestyle Study.

PURPOSE: Use of complementary and alternative medicine (CAM) is common among breast cancer patients, but less is known about whether CAM influences breast cancer survival. METHODS: Health Eating, Activity, and Lifestyle (HEAL) Study participants (n = 707) were diagnosed with stage I-IIIA breast cancer. Participants completed a 30-month post-diagnosis interview including questions on CAM use (natural products such as dietary and botanical supplements, alternative health practices, and alternative medical systems), weight, physical activity, and comorbidities. Outcomes were breast cancer-specific and total mortality, which were ascertained from the Surveillance Epidemiology and End Results registries in Western Washington, Los Angeles County, and New Mexico. Cox proportional hazards regression models were fit to data to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for mortality. Models were adjusted for potential confounding by sociodemographic, health, and cancer-related factors. RESULTS: Among 707 participants, 70 breast cancer-specific deaths and 149 total deaths were reported. 60.2 % of participants reported CAM use post-diagnosis. The most common CAM were natural products (51 %) including plant-based estrogenic supplements (42 %). Manipulative and body-based practices and alternative medical systems were used by 27 and 13 % of participants, respectively. No associations were observed between CAM use and breast cancer-specific (HR 1.04, 95 % CI 0.61-1.76) or total mortality (HR 0.91, 95 % CI 0.63-1.29). CONCLUSION: Complementary and alternative medicine use was not associated with breast cancer-specific mortality or total mortality. Randomized controlled trials may be needed to definitively test whether there is harm or benefit from the types of CAM assessed in HEAL in relation to mortality outcomes in breast cancer survivors.

Obesity, maternal smoking and SHBG in neonates.

BACKGROUND: Sex hormone binding globulin (SHBG), a glycoprotein produced by hepatocytes that transports testosterone and other steroids in plasma, is a marker for developing metabolic syndrome and T2DM. SHBG is present in umbilical cord blood where it may be epigenetically regulated. This study was conducted to investigate whether the fetal environment, based on maternal pre-pregnancy weight, pregnancy weight gain or smoking during pregnancy, influence SHBG in newborns. METHODS: Maternal and newborn characteristics and SHBG levels and other variables were measured in cord and day 2 heel-stick blood samples in 60 healthy full-term singleton babies (31 F, 29 M). RESULTS: SHBG levels varied nearly fivefold among male and female newborns and were unrelated to sex, neonatal adiposity, determined by the Ponderal index and skinfold thickness, nor TNF∝ in cord blood. There were also no statistically significant associations between pre-pregnancy weight or pregnancy weight gain and newborn SHBG levels. However, cord blood SHBG was higher and insulin levels were lower when mothers were smokers, but normalized by day 2. DISCUSSION: While SHBG levels are low in obese children and adults, and portend the development of metabolic syndrome and T2DM, our study of healthy babies born to normal women, found no connection between maternal obesity or newborn adiposity and SHBG levels in newborns. Insofar as women who smoked during pregnancy were thinner and had lower cord blood insulin levels than nonsmokers, higher SHBG in their newborns at birth might have been due to insulin sensitivity, or perhaps to an effect of smoking on placental gene expression. CONCLUSIONS: Factors other than maternal weight and pregnancy weight gain appear to be the major determinants of SHBG in newborns. Higher SHBG levels when mothers smoke during pregnancy may contribute to overweight beginning later in childhood. Whether newborn SHBG levels predict the development of overweight and metabolic syndrome remains to be determined.

Ethnic differences in the relationships between diabetes, early age adiposity and mortality among breast cancer survivors: the Breast Cancer Health Disparities Study.

The contribution of type 2 diabetes and obesity on mortality in breast cancer (BC) patients has not been well studied among Hispanic women, in whom these exposures are highly prevalent. In a multi-center population-based study, we examined the associations between diabetes, multiple obesity measures, and mortality in 1180 Hispanic and 1298 non-Hispanic white (NHW) women who were diagnosed with incident invasive BC from the San Francisco Bay Area, New Mexico, Utah, Colorado, and Arizona. Adjusted hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards regression models. The median follow-up time from BC diagnosis to death was 10.8 years. In ethnic-stratified results, the association for BC-specific mortality among Hispanics was significantly increased (HR 1.85 95 % CI 1.11, 3.09), but the ethnic interaction was not statistically significant. In contrast, obesity at age 30 increased BC-specific mortality risk in NHW women (HR 2.33 95 % CI 1.36, 3.97) but not Hispanics (p-interaction = 0.045). Although there were no ethnic differences for all-cause mortality, diabetes, obesity at age 30, and post-diagnostic waist-hip ratio were significantly associated with all-cause mortality in all women. This study provides evidence that diabetes and adiposity, both modifiable, are prognostic factors among Hispanic and NHW BC patients.

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.

Associations of sex steroid hormones with mortality in women with breast cancer.

Epidemiological studies have demonstrated associations between circulating levels of sex steroid hormones and risk of breast cancer in postmenopausal women. However, data on associations with breast cancer survival are limited. We measured levels of estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG), in serum collected on average 30 months after diagnosis from 358 postmenopausal women diagnosed with stage I-IIIA breast cancer between 1995 and 1998 who participated in a multiethnic, prospective cohort study. Women were followed through December, 2012. We evaluated associations between log-transformed analytes and breast cancer-specific and all-cause mortality fitting multivariable Cox proportional hazards models. Over a median of 14.5 years of follow-up, 102 deaths occurred; 43 of these were due to breast cancer. In models adjusted for ethnicity/study site, age, body mass index, and tumor stage, increased levels of log-transformed SHBG were associated with reduced risk of both breast cancer-specific mortality (hazard ratio, HR 0.48; 95 % confidence interval, CI 0.26-0.89) and all-cause mortality (HR 0.64, 95 % CI 0.43-0.97). There were no associations between levels of estradiol, estrone, or testosterone for either endpoint. In subgroup analyses, after correction for multiple testing, increased estrone was significantly associated with reduced risk for breast cancer-specific mortality among participants with ER-negative tumors (HR 0.16, 95 % CI 0.05-0.63) but not among participants with ER-positive tumors. Increased serum levels of SHBG were associated with decreased risk of breast cancer-specific and all-cause mortality in women with breast cancer. These results should be confirmed in larger breast cancer survivor cohorts.

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.