Publications by authors named "Kathy B Baumgartner"

113 Publications

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

NPJ Breast Cancer 2020 9;6:51. Epub 2020 Oct 9.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA.

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 (-interaction= 0.03) and with localized stage (-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.
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http://dx.doi.org/10.1038/s41523-020-00194-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547070PMC
October 2020

Menstrual and reproductive characteristics and breast cancer risk by hormone receptor status and ethnicity: The Breast Cancer Etiology in Minorities study.

Int J Cancer 2020 Oct 29;147(7):1808-1822. Epub 2020 Feb 29.

Department of Preventive Medicine, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA.

We pooled multiethnic data from four population-based studies and examined associations of menstrual and reproductive characteristics with breast cancer (BC) risk by tumor hormone receptor (HR) status [defined by estrogen receptor (ER) and progesterone receptor (PR)]. We estimated odds ratios and 95% confidence intervals using multivariable logistic regression, stratified by age (<50, ≥50 years) and ethnicity, for 5,186 HR+ (ER+ or PR+) cases, 1,365 HR- (ER- and PR-) cases and 7,480 controls. For HR+ BC, later menarche and earlier menopause were associated with lower risk in non-Hispanic whites (NHWs) and Hispanics, and higher parity and longer breast-feeding were associated with lower risk in Hispanics and Asian Americans, and suggestively in NHWs. Positive associations with later first full-term pregnancy (FTP), longer interval between menarche and first FTP and shorter time since last FTP were limited to younger Hispanics and Asian Americans. Except for nulliparity, reproductive characteristics were not associated with risk in African Americans. For HR- BC, lower risk was associated with later menarche, except in African Americans and older Asian Americans and with longer breast-feeding in Hispanics and Asian Americans only. In younger African Americans, HR- BC risk associated with higher parity (≥3 vs. 1 FTP) was increased fourfold in women who never breast-fed, but not in those with a breast-feeding history, suggesting that breast-feeding may mitigate the adverse effect of higher parity in younger African American women. Further work needs to evaluate why menstrual and reproductive risk factors vary in importance according to age and ethnicity.
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http://dx.doi.org/10.1002/ijc.32923DOI Listing
October 2020

A Pooled Analysis of Breastfeeding and Breast Cancer Risk by Hormone Receptor Status in Parous Hispanic Women.

Epidemiology 2019 05;30(3):449-457

From the Cancer Prevention Institute of California, Fremont, CA.

Background: Data on breastfeeding and breast cancer risk are sparse and inconsistent for Hispanic women.

Methods: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the United States and Mexico, we examined the association of breastfeeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, and the joint effects of breastfeeding, parity, and age at first birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression.

Results: Among parous Hispanic women, older age at first birth was associated with increased breast cancer risk, whereas parity was associated with reduced risk. These associations were found for hormone receptor positive (HR+) breast cancer only and limited to premenopausal women. Age at first birth and parity were not associated with risk of ER- and PR- breast cancer. Increasing duration of breastfeeding was associated with decreasing breast cancer risk (≥25 vs. 0 months: OR = 0.73; 95% CI = 0.60, 0.89; Ptrend = 0.03), with no heterogeneity by menopausal status or subtype. At each parity level, breastfeeding further reduced HR+ breast cancer risk. Additionally, breastfeeding attenuated the increase in risk of HR+ breast cancer associated with older age at first birth.

Conclusions: Our findings suggest that breastfeeding is associated with reduced risk of both HR+ and ER- and PR- breast cancer among Hispanic women, as reported for other populations, and may attenuate the increased risk in women with a first pregnancy at older ages.
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http://dx.doi.org/10.1097/EDE.0000000000000981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472273PMC
May 2019

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

NPJ Breast Cancer 2019 7;5. Epub 2019 Jan 7.

2Department of Epidemiology and Population Health and the James Graham Brown Cancer Center, University of Louisville, Louisville, KY USA.

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.
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http://dx.doi.org/10.1038/s41523-018-0099-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323117PMC
January 2019

Reproductive history, breast-feeding and risk of triple negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) study.

Int J Cancer 2018 06 30;142(11):2273-2285. Epub 2018 Jan 30.

Department of Preventive Medicine, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA.

Few risk factors have been identified for triple negative breast cancer (TNBC) which lacks expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). This more aggressive subtype disproportionately affects some racial/ethnic minorities and is associated with lower survival. We pooled data from three population-based studies (558 TNBC and 5,111 controls) and examined associations of TNBC risk with reproductive history and breast-feeding. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression. For younger women, aged <50 years, TNBC risk was increased two-fold for parous women who never breast-fed compared to nulliparous women (OR = 2.02, 95% CI = 1.12-3.63). For younger parous women, longer duration of lifetime breast-feeding was associated with a borderline reduced risk (≥24 vs. 0 months: OR = 0.52, 95% CI = 0.26-1.04, P  = 0.06). Considering the joint effect of parity and breast-feeding, risk was increased two-fold for women with ≥3 full-term pregnancies (FTPs) and no or short-term (<12 months) breast-feeding compared to women with 1-2 FTPs and breast-feeding ≥12 months (OR = 2.56, 95% CI = 1.22-5.35). None of these associations were observed among older women (≥50 years). Differences in reproductive patterns possibly contribute to the ethnic differences in TNBC incidence. Among controls aged <50 years, the prevalence of no or short-term breast-feeding and ≥3 FTPs was highest for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%) and non-Hispanic whites (6%). Breast-feeding is a modifiable behavioral factor that may lower TNBC risk and mitigate the effect of FTPs in women under age 50 years.
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http://dx.doi.org/10.1002/ijc.31258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893409PMC
June 2018

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

Breast Cancer Res Treat 2018 Apr 18;168(2):567-576. Epub 2017 Dec 18.

Epidemiology Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

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 G > A (rs1800629); PPARγ ProAla (rs1801282); and IRS-1 GlyArg (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 G > A polymorphism was associated with reduced breast-cancer-specific and all-cause mortality.
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http://dx.doi.org/10.1007/s10549-017-4621-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839976PMC
April 2018

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.

Breast Cancer Res Treat 2018 Apr 30;168(2):443-455. Epub 2017 Nov 30.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Office E-6144, Baltimore, MD, USA.

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 (HR = 1.40; 95% CI 1.13-1.73, P  = 0.018). The rs1424482 CC genotype (HR = 1.69; 95% CI 1.20-2.37, P  = 0.027) and the rs7027604 AA genotype (HR = 1.65; 95% CI 1.21-2.26, P  = 0.018) were positively associated with non-BC mortality. Among long-term light drinkers, rs1888202 was associated with decreased all-cause mortality (HR = 0.36; 95% CI 0.20-0.64), while associations were not significant among non-drinkers or moderate/heavy drinkers (P  = 0.218). The increased risk of all-cause mortality associated with rs63319 was limited to women with low NA ancestry (HR = 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.
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http://dx.doi.org/10.1007/s10549-017-4600-2DOI Listing
April 2018

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

Breast Cancer Res Treat 2018 01 31;167(1):171-181. Epub 2017 Aug 31.

Department of Epidemiology and Population Health, School of Public Health and Information Sciences, James Graham Brown Cancer Center, University of Louisville, 485 E. Gray St., Louisville, KY, 40202, USA.

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.
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http://dx.doi.org/10.1007/s10549-017-4467-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830105PMC
January 2018

The Interaction between Genetic Ancestry and Breast Cancer Risk Factors among Hispanic Women: The Breast Cancer Health Disparities Study.

Cancer Epidemiol Biomarkers Prev 2017 05 8;26(5):692-701. Epub 2016 Dec 8.

Department of Medicine, University of Utah, Salt Lake City, Utah.

Hispanic women have lower breast cancer incidence rates than non-Hispanic white (NHW) women. To what extent genetic versus nongenetic factors account for this difference is unknown. Using logistic regression, we evaluated the interactive influences of established risk factors and ethnicity (self-identified and identified by ancestral informative markers) on breast cancer risk among 2,326 Hispanic and 1,854 NHW postmenopausal women from the United States and Mexico in the Breast Cancer Health Disparities Study. The inverse association between the percentage of Native American (NA) ancestry and breast cancer risk was only slightly attenuated after adjusting for known risk factors [lowest versus highest quartile: odds ratio (OR) =1.39, 95% confidence interval (CI) = 1.00-1.92 among U.S. Hispanics; OR = 1.92 (95% CI, 1.29-2.86) among Mexican women]. The prevalence of several risk factors, as well as the associations with certain factors and breast cancer risk, differed according to genetic admixture. For example, higher body mass index (BMI) was associated with reduced risk among women with lower NA ancestry only [BMI <25 versus >30: OR = 0.65 (95% CI, 0.44-0.98) among U.S. Hispanics; OR = 0.53 (95% CI, 0.29-0.97) among Mexicans]. The average number of risk factors among cases was inversely related to the percentage of NA ancestry. The lower NA ancestry groups were more likely to have the established risk factors, with the exception of BMI. Although the majority of factors were associated with risk in the expected directions among all women, BMI had an inverse association among Hispanics with lower NA ancestry. These data suggest that the established risk factors are less relevant for breast cancer development among women with more NA ancestry. .
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http://dx.doi.org/10.1158/1055-9965.EPI-16-0721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413419PMC
May 2017

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

Breast Cancer Res Treat 2017 01 11;161(2):321-331. Epub 2016 Nov 11.

Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.

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/m, while positive associations were observed among women with BMI ≥25 kg/m (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.
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http://dx.doi.org/10.1007/s10549-016-4048-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226868PMC
January 2017

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

Breast Cancer Res Treat 2016 12 21;160(3):539-546. Epub 2016 Oct 21.

Office of Disease Prevention, National Institutes of Health, Bethesda, MD, USA.

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.
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http://dx.doi.org/10.1007/s10549-016-4010-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558457PMC
December 2016

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

Breast Cancer Res Treat 2016 05 26;157(1):167-78. Epub 2016 Apr 26.

Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.

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.
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http://dx.doi.org/10.1007/s10549-016-3810-3DOI Listing
May 2016

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

Cancer Epidemiol 2016 06 18;42:108-14. Epub 2016 Apr 18.

University of Louisville, School of Medicine, Departments of Community and Geriatric Medicine, Obstetrics & Gynecology, Louisville, KY, USA; University of Louisville, School of Public Health and Information Sciences, Departments of Epidemiology & Population Health and Health Promotion & Behavioral Health Sciences, Louisville, KY, USA; University of Louisville, School of Engineering, Department of Bioengineering, Louisville, KY, USA.

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.
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http://dx.doi.org/10.1016/j.canep.2016.04.003DOI Listing
June 2016

Red meat, poultry, and fish intake and breast cancer risk among Hispanic and Non-Hispanic white women: The Breast Cancer Health Disparities Study.

Cancer Causes Control 2016 Apr 22;27(4):527-43. Epub 2016 Feb 22.

Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine of USC, University of Southern California, 1441 Eastlake Avenue, Room 5421A, Los Angeles, CA, 90089, USA.

Purpose: There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women.

Methods: The study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case-control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels.

Results: When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05-1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95% CI 1.18-1.71; trend p < 0.001), and between white meat (OR 0.80; 95% CI 0.67-0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models and were restricted to estrogen receptor-positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups.

Conclusions: Our results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities.
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http://dx.doi.org/10.1007/s10552-016-0727-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821634PMC
April 2016

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

Breast Cancer Res Treat 2016 Feb 10;155(3):559-67. Epub 2016 Feb 10.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

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.
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http://dx.doi.org/10.1007/s10549-016-3704-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793898PMC
February 2016

Adherence to cervical cancer screening varies by human papillomavirus vaccination status in a high-risk population.

Prev Med Rep 2015 31;2:711-6. Epub 2015 Jul 31.

University of Louisville, School of Public Health and Information Sciences, Department of Epidemiology and Population Health, Louisville, KY, USA; University of Louisville, School of Medicine, Department of Family and Geriatric Medicine, Louisville, KY, USA; University of Louisville, School of Medicine, Department of Obstetrics and Gynecology, Louisville, KY, USA; University of Louisville, School of Public Health and Information Sciences, Department of Health Promotion and Behavioral Health Sciences, Louisville, KY, USA; University of Louisville, Speed School of Engineering, Department of Bioengineering, Louisville, KY, USA.

Cervical cancer screening has reduced the incidence of cervical cancer over the past 75 years. The primary aim of this study was to determine if women receiving Gardasil™ (HPV4 vaccine) participated in future cervical cancer screening at the same rate as that observed for unvaccinated women matched on birth year and health care campus. This is a retrospective cohort study of subjects selected from 27,786 females born from 1980 to 1992 who received health care in the Truman Medical Center safety net health system in Kansas City Missouri, USA. 1154 women 14-26 years old who received at least one dose of HPV4 vaccine between 2006 and 2009 were chosen at random from the vaccine records. 1154 randomly chosen unvaccinated women were age and health campus matched to the vaccinated women and all were followed until July 1, 2013. Women who were screened after 21 years and received three vaccine doses before 21 years, had the lowest screening rate of 24%. Their only predictive factor for screening, compared to the unvaccinated, was being closer to 21 years than 14 years at vaccination (aOR = 1.71 95% CI: 1.45, 2.00). Women vaccinated with three doses and screened at or after 21 years had the highest screening rate of 84% predicting a six-fold increase in screening participation over no vaccine received (aOR = 5.94 95% CI: 3.77, 9.35). Our results suggest that women who receive HPV4 vaccination closer to 21 years, not 14, are more likely to participate in cervical cancer screening in an underserved US population.
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http://dx.doi.org/10.1016/j.pmedr.2015.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721469PMC
February 2016

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

J Womens Health (Larchmt) 2016 Mar 18;25(3):299-310. Epub 2015 Dec 18.

8 Department of Internal Medicine, University of Utah , Salt Lake City, Utah.

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.
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http://dx.doi.org/10.1089/jwh.2015.5502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790199PMC
March 2016

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

Cancer Causes Control 2016 Jan 30;27(1):115-24. Epub 2015 Oct 30.

Department of Epidemiology and Population Health, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.

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 (β = -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 β = -10.51, p = 0.004; follow-up β = -7.16, p = 0.02) and controls (baseline β = -11.07, p < 0.001; follow-up β = -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.
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http://dx.doi.org/10.1007/s10552-015-0688-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871242PMC
January 2016

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

Ann Epidemiol 2015 Nov 28;25(11):824-31. Epub 2015 Aug 28.

Department of Internal Medicine, University of Utah, Salt Lake City.

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.
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http://dx.doi.org/10.1016/j.annepidem.2015.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609618PMC
November 2015

Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women.

Cancer Epidemiol Biomarkers Prev 2015 Nov 12;24(11):1731-8. Epub 2015 Sep 12.

Department of Medicine, University of Utah, Salt Lake City, Utah.

Background: Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population.

Methods: We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions.

Results: We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, <12 months, and >12 months breastfeeding, respectively, Pinteraction 0.014].

Conclusions: The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women.

Impact: These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-15-0392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633366PMC
November 2015

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

J Cancer Surviv 2015 Sep 26;9(3):422-30. Epub 2015 Apr 26.

Department of Epidemiology and Population Health, University of Louisville, Louisville, KY, 40202, USA.

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.
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http://dx.doi.org/10.1007/s11764-014-0416-9DOI Listing
September 2015

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

J Cancer Surviv 2015 Dec 5;9(4):650-9. Epub 2015 Mar 5.

Department of Epidemiology and Population Health, School of Public Health and Information Sciences, James Graham Brown Cancer Center, University of Louisville, 485 E. Gray St., Louisville, 40202, KY, USA.

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.
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http://dx.doi.org/10.1007/s11764-015-0441-3DOI Listing
December 2015

MAPK genes interact with diet and lifestyle factors to alter risk of breast cancer: the Breast Cancer Health Disparities Study.

Nutr Cancer 2015 28;67(2):292-304. Epub 2015 Jan 28.

a Department of Medicine , University of Utah , Salt Lake City , Utah , USA.

Mitogen-activated protein kinases (MAPK) are integration points for multiple biochemical signals. We evaluated 13 MAPK genes with breast cancer risk and determined if diet and lifestyle factors mediated risk. Data from 3 population-based case-control studies conducted in Southwestern United States, California, and Mexico included 4183 controls and 3592 cases. Percent Indigenous American (IA) ancestry was determined from 104 ancestry informative markers. The adaptive rank truncated product (ARTP) was used to determine the significance of each gene and the pathway with breast cancer risk, by menopausal status, genetic ancestry level, and estrogen receptor (ER)/progesterone receptor (PR) strata. MAP3K9 was associated with breast cancer overall (P(ARTP) = 0.02) with strongest association among women with the highest IA ancestry (P(ARTP) = 0.04). Several SNPs in MAP3K9 were associated with ER+/PR+ tumors and interacted with dietary oxidative balance score (DOBS), dietary folate, body mass index (BMI), alcohol consumption, cigarette smoking, and a history of diabetes. DUSP4 and MAPK8 interacted with calories to alter breast cancer risk; MAPK1 interacted with DOBS, dietary fiber, folate, and BMI; MAP3K2 interacted with dietary fat; and MAPK14 interacted with dietary folate and BMI. The patterns of association across diet and lifestyle factors with similar biological properties for the same SNPs within genes provide support for associations.
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http://dx.doi.org/10.1080/01635581.2015.990568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450722PMC
December 2015

Overall and abdominal adiposity and premenopausal breast cancer risk among hispanic women: the breast cancer health disparities study.

Cancer Epidemiol Biomarkers Prev 2015 Jan 28;24(1):138-47. Epub 2014 Oct 28.

Department of Medicine, University of Utah, Salt Lake City, Utah.

Background: Few studies in Hispanic women have examined the relation between adult body size and risk of premenopausal breast cancer defined by hormone receptor status.

Methods: The Breast Cancer Health Disparities Study pooled interview and anthropometric data from two large U.S. population-based case-control studies. We examined associations of overall and abdominal adiposity with risk of estrogen receptor- and progesterone receptor-positive (ER(+)PR(+)) and -negative (ER(-)PR(-)) breast cancer in Hispanic and non-Hispanic White (NHW) women, calculating ORs and 95% confidence intervals.

Results: Among Hispanics, risk of ER(+)PR(+) breast cancer was inversely associated with measures of overall adiposity, including young-adult and current body mass index (BMI). Risk was substantially reduced among those with high (above the median) young-adult BMI and current overweight or obesity. The findings for overall adiposity were similar for Hispanics and NHWs. In the subset of Hispanics with data on genetic ancestry, inverse associations of current BMI, and weight gain with ER(+)PR(+) breast cancer were limited to those with lower Indigenous American ancestry. For ER(-)PR(-) breast cancer, height was associated with increased risk, and young-adult BMI was associated with reduced risk. For all breast cancers combined, positive associations were seen for waist circumference, waist-to-hip ratio, and waist-to-height ratio in Hispanic women only.

Conclusions: Our findings of body size associations with specific breast cancer subtypes among premenopausal Hispanic women were similar to those reported for NHW women.

Impact: Adiposity throughout the premenopausal years has a major influence on breast cancer risk in Hispanic women.
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http://dx.doi.org/10.1158/1055-9965.EPI-13-1007-TDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294975PMC
January 2015

Body size throughout adult life influences postmenopausal breast cancer risk among hispanic women: the breast cancer health disparities study.

Cancer Epidemiol Biomarkers Prev 2015 Jan 28;24(1):128-37. Epub 2014 Oct 28.

Department of Medicine, University of Utah, Salt Lake City, Utah.

Background: Few studies have assessed the association of body size with postmenopausal breast cancer risk in Hispanic women. Findings are inconsistent and appear to contradict those reported for non-Hispanic white (NHW) women.

Methods: We pooled interview and anthropometric data for 2,023 Hispanic and 2,384 NHW women from two U.S. population-based case-control studies. Using logistic regression analysis, we examined associations of overall and abdominal adiposity with risk of postmenopausal breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status.

Results: Weight gain was associated with increased risk of ER(+)PR(+) breast cancer in Hispanics not currently using menopausal hormone therapy (HT), but only among those with a low young-adult body mass index (BMI). In the subset of Hispanics with data on genetic ancestry, the association with weight gain was limited to women with lower Indigenous American ancestry. Young-adult BMI was inversely associated with both ER(+)PR(+) and ER(-)PR(-) breast cancers for both ethnicities combined, with similar, although nonsignificant, inverse trends in Hispanics and NHWs. Among all Hispanics, regardless of HT use, height was associated with risk of ER(-)PR(-) breast cancer and hip circumference with risk of breast cancer overall.

Conclusions: Body size throughout adult life is associated with breast cancer risk among postmenopausal Hispanic women, as has been reported for NHW women. Associations were specific for breast cancer subtypes defined by hormone receptor status.

Impact: Avoiding weight gain and maintaining a healthy weight are important strategies to reduce the risk of postmenopausal ER(+)PR(+) breast cancer, the most common breast cancer subtype.
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http://dx.doi.org/10.1158/1055-9965.EPI-14-0560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295775PMC
January 2015

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

Mol Carcinog 2015 Dec 22;54(12):1541-53. Epub 2014 Oct 22.

Department of Internal Medicine, University of Utah, Salt Lake City, Utah.

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.
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http://dx.doi.org/10.1002/mc.22228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406776PMC
December 2015

Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study.

Breast Cancer Res 2014 Aug 22;16(4):414. Epub 2014 Aug 22.

Introduction: Lymphedema is a potentially debilitating condition that occurs among breast cancer survivors. This study examines the incidence of self-reported lymphedema, timing of lymphedema onset, and associations between sociodemographic, clinical and lifestyle factors and lymphedema risk across racial-ethnic groups using data from a multicenter, multiethnic prospective cohort study of breast cancer survivors, the Health, Eating, Activity and Lifestyle Study.

Methods: A total of 666 women diagnosed with breast cancer staged as in situ, localized or regional disease at ages 35 to 64 years were recruited through the Surveillance, Epidemiology, and End Results registries in New Mexico (non-Hispanic white and Hispanic white), Los Angeles County (black), and Western Washington (non-Hispanic white) and followed for a median of 10.2 years. We evaluated sociodemographic factors, breast cancer- and treatment-related factors, comorbidities, body mass index (BMI), hormonal factors, and lifestyle factors in relation to self-reported lymphedema by fitting Cox proportional hazards models, estimating hazard ratios (HR) and 95% confidence intervals (CI).

Results: Over the follow-up period, 190 women (29%) reported lymphedema. The median time from breast cancer diagnosis to onset of lymphedema was 10.5 months (range: 0.5 to 134.9 months). Factors independently associated with lymphedema were total/modified radical mastectomy (versus partial/less than total mastectomy; HR = 1.37, 95% CI: 1.01 to 1.85), chemotherapy (versus no chemotherapy; HR = 1.48, 95% CI: 1.09 to 2.02), no lymph nodes removed (versus ≥10 lymph nodes removed; HR = 0.17, 95% CI: 0.08 to 0.33), pre-diagnostic BMI ≥30 kg/m2 (versus BMI <25 kg/m2; HR = 1.59, 95% CI: 1.09 to 2.31), and hypertension (versus no hypertension; HR = 1.49, 95% CI: 1.06 to 2.10). After adjusting for demographics and breast cancer- and treatment-related factors, no significant difference in lymphedema risk was observed across racial/ethnic groups. Analyses stratified by race/ethnicity showed that hypertension and chemotherapy were lymphedema risk factors only for black women.

Conclusions: Breast cancer patients who have undergone extensive surgery or extensive lymph node dissection, or who have a higher BMI should be closely monitored for detection and treatment of lymphedema. Further studies are needed to understand the roles of chemotherapy and hypertension in the development of lymphedema.
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http://dx.doi.org/10.1186/s13058-014-0414-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189147PMC
August 2014

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

Cancer Causes Control 2014 Nov 5;25(11):1461-71. Epub 2014 Aug 5.

Department of Epidemiology and Population Health, James Graham Brown Cancer Center, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray St., Louisville, KY, 40202, USA,

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.
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http://dx.doi.org/10.1007/s10552-014-0448-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435673PMC
November 2014

Central adiposity after breast cancer diagnosis is related to mortality in the Health, Eating, Activity, and Lifestyle study.

Breast Cancer Res Treat 2014 Aug 24;146(3):647-55. Epub 2014 Jul 24.

Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA,

We examined whether waist circumference (WC) and waist-to-hip ratio (WHR) after breast cancer diagnosis are associated with all-cause or breast cancer-specific mortality and explored potential biological pathways mediating these relationships. Our analysis included 621 women diagnosed with local or regional breast cancer who participated in the Health, Eating, Activity, and Lifestyle study. At 30 (±4) months postdiagnosis, trained staff measured participants' waist and hip circumferences and obtained fasting serum samples for biomarker assays for assays of insulin, glucose, C-peptide, insulin growth factor-1 and binding protein-3, C-reactive protein (CRP), and adiponectin. We estimated multivariate hazard ratios (HR) and 95 % confidence intervals (CI) for death over ~9.5 years of follow-up. After adjustment for measured body mass index, treatment, comorbidities, race/ethnicity, diet quality, and postdiagnosis physical activity, WC was positively associated with all-cause mortality (HRq4:q1: 2.99, 95 % CI 1.14, 7.86) but its positive association with breast cancer-specific mortality was not statistically significant (HRq4:q1: 2.69, 95 % CI 0.69, 12.01). WHR was positively associated with all-cause mortality (HRq4:q1: 2.10, 95 % CI 1.08, 4.05) and breast cancer-specific mortality (HRq4:q1: 4.02, 95 % CI 1.31, 12.31). After adjustment for homeostatic model assessment (HOMA) score and C-reactive protein, risk estimates were attenuated and not statistically significant. In this diverse breast cancer survivor cohort, postdiagnosis WC and WHR were associated with all-cause mortality. Insulin resistance and inflammation may mediate the effects of central adiposity on mortality among breast cancer patients.
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http://dx.doi.org/10.1007/s10549-014-3048-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996589PMC
August 2014