Sedentary time and breast cancer incidence in African American women

Purpose

The objective of this study was to evaluate whether time spent sitting at work or watching television was associated with breast cancer risk among African American women.

Methods

The Black Women’s Health Study (analytic cohort = 46,734) is an ongoing prospective cohort study of African American women ages 21–69 at baseline (1995). Questionnaire data were used to estimate sedentary time. Total time spent sitting at work and watching television (individually and combined) at baseline and updated through follow-up (1995–2001) and breast cancer incidence (n = 2,041 incident cases, 1995–2013) was evaluated using proportional hazards regression.

Results

Higher total time spent sitting at baseline (≥10 vs. <5 h/day, HR 1.27, 95 % CI 1.06, 1.53) and updated through follow-up (≥10 vs. <5 h/day, HR 1.38, 95 % CI 1.14, 1.66) was associated with an increased breast cancer risk. Associations were stronger for hormone receptor-negative tumors (≥10 vs. <5 h/day, HR 1.70, 95 % CI 1.12, 2.55) compared to hormone receptor-positive tumors (≥10 vs. <5 h/day, HR 1.16, 95 % CI 0.88, 1.52), but tests for heterogeneity were not statistically significant (p heterogeneity = 0.31). Positive associations between total time spent sitting and breast cancer incidence did not differ by physical activity level or body composition measurements.

Conclusions

Our findings suggest that high sedentary time may increase risk for breast cancer among African American women.

     

Alcohol intake and invasive breast cancer risk by molecular subtype and race in the Carolina Breast Cancer Study

Purpose

Alcohol is an established breast cancer risk factor, but there is little evidence on whether the association differs between African Americans and whites.

Methods

Invasive breast cancers (n = 1,795; 1,014 white, 781 African American) and age- and race-matched controls (n = 1,558; 844 white, 714 African American) from the Carolina Breast Cancer Study (Phases I–II) were used to estimate odds ratios (ORs) and 95 % confidence interval (CI) for pre-diagnosis drinks per week and breast cancer risk.

Results

African American controls reported lower alcohol intake than white controls across all age groups. Light drinking (0 to ≤2 per week) was more prevalent among African American controls. Moderate-to-heavy drinking was more prevalent in white controls. African Americans who reported drinking >7 drinks per week had an elevated risk compared to light drinkers [adjusted OR, 95% CI 1.62 (1.03–2.54)]. A weaker association was observed among whites [adjusted OR, 95% CI 1.20 (0.87–1.67)]. The association of >7 drinks per week with estrogen receptor-negative [adjusted OR, 95% CI 2.17 (1.25–3.75)] and triple-negative [adjusted OR, 95% CI 2.12 (1.12–4.04)] breast cancers was significant for African American, but not white women. We observed significantly elevated ORs for heavy intake at ages <25 and >50 years of age for African American women only. We found no evidence of statistical interaction between alcohol intake and oral contraceptive use or smoking.

Conclusions

Drinking more than seven alcoholic beverages per week increased invasive breast cancer risk among white and African American women, with significant increases only among African American women. Genetic or environmental factors that differ by race may mediate the alcohol–breast cancer risk association.

     

Swedish prospective multicenter trial evaluating sentinel lymph node biopsy after neoadjuvant systemic therapy in clinically node-positive breast cancer

Purpose

The clinical significance of nodal micrometastasis is debated. Our primary objective was to determine whether, among women with early-stage breast cancer, regional lymph node micrometastasis is an independent risk factor for mortality. The secondary objective was to identify subgroups of women who have the highest risk of death from early-stage breast cancer with micrometastases.

Methods

206,625 women diagnosed with early-stage breast cancer (IA, IB, and IIA) from 2004 to 2012 were identified in the Surveillance, epidemiology, and end results database. Nodal status was classified as node-negative, isolated-tumor cells, micrometastases, and macrometastases. Women were classified into eight ethnic groups. Logistic regression was performed to estimate the odds ratio of being diagnosed with micrometastases. The Cox proportional hazard model was used to estimate the hazard ratio (HR) of breast cancer-specific death associated with micrometastases for each ethnic group.

Results

The 8-year breast cancer-specific survival was 96.6 % for women with node-negative breast cancers and was 94.6 % for women with micrometastases (adjusted HR 1.49; 95 % CI 1.31–1.69; P < .001). Among women with micrometastases, the 8-year breast cancer-specific survival was 95.1 % for white women and was 90.6 % for black women (HR 1.80; 95 % CI 1.29–2.52; P = .0006).

Conclusion(s)

Nodal micrometastasis is an independent risk factor for breast cancer mortality among women with early-stage breast cancer. Black women are more likely to die from breast cancer with micrometastases than white women.

     

African American patients with breast cancer have worse prognosis than white patients in certain subtypes and stages

Purpose

Racial disparity of breast cancer in each subtype and substage is not clear.

Methods

We reviewed 156,938 patients with breast cancer from 2010 to 2012 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Breast cancer was subtyped by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status as HR+/HER2?, HR+/HER2+, HR?/HER2+, and HR?/HER2?.

Results

African American (AA) patients had worse overall survival (OS) and breast cancer cause-specific survival (BCSS) in HR+/HER2? stages III and IV breast cancer and HR?/HER2+ stage IV cancer; they had worse OS but not BCSS in HR+ /HER2? stage II cancer and HR?/HER2? stage II cancer.

Conclusion

AA patients with breast cancer had worse survival in certain subtype and stage, especially in ER+ breast cancer.

     

Racial differences in prostate cancer risk in young HIV-positive and HIV-negative men: a prospective cohort study

Purpose

African American men have the highest incidence of prostate cancer among ethnic groups, and racial disparity is highest in younger men. Prostate cancer prevalence is rising in HIV-infected men due to improved survival on antiretroviral therapies, yet little is known about racial differences in prostate cancer risk by HIV-infection status and age.

Methods

This is a prospective cohort study of prostate cancer risk in 2,800 HIV-infected and -uninfected men who have sex with men (MSM) aged 40–70 years (22% African American) who were enrolled in the multicenter AIDS cohort study from 1996 to 2010. Poisson regression models were used to examine associations between race and HIV-infection status and prostate cancer risk among men aged 40–70, 40–55, and 56–70 years.

Results

Among men aged 40–70 years, incidence rates (IR) per 100,000 person-years were 169 among all men and 276 among African American HIV-infected men. Prostate cancer risk was similar by HIV-infection status (IRR 1.0, 95% CI 0.55–1.82), but nearly threefold higher in African Americans compared to non-African Americans in adjusted models (IRRs 2.66 and 3.22, 95% CIs 1.36–5.18 and 1.27–8.16 for all or HIV-infected men, respectively). Racial disparity in prostate cancer risk was greatest in African American men aged 40–55 years (adjusted IRR 3.31, 95% CI 1.19–9.22). Prostate cancer risk showed associations with family history of prostate cancer (p = 0.001), but not heavy smoking, androgen supplement use, or HIV-related factors.

Conclusions

Among MSM, African American HIV-positive and HIV-negative men aged 40–55 years have threefold increased risk of young-onset prostate cancer compared to non-African American men, highlighting the need to make informed decisions about screening in this population.

     

Trastuzumab uptake and its relation to efficacy in an animal model of HER2-positive breast cancer brain metastasis

Purpose

To examine whether baseline sleep duration or changes in sleep duration are associated with breast cancer prognosis among early-stage breast cancer survivors in the multi-center Women’s Healthy Eating and Living Study.

Methods

Data were collected from 1995 to 2010. Analysis included 3047 women. Sleep duration was self-reported at baseline and follow-up intervals. Cox proportional hazard models were used to investigate whether baseline sleep duration was associated with breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality. Time-varying models investigated whether changes in sleep duration were associated with breast cancer prognosis.

Results

Compared to women who slept 7–8 h/night at baseline, sleeping ≥9 h/night was associated with a 48% increased risk of breast cancer recurrence (Hazard ratio [HR] 1.48, 95% Confidence interval [CI] 1.01, 2.00), a 52% increased risk of breast cancer-specific mortality (HR 1.52, 95% CI 1.09, 2.13), and a 43% greater risk of all-cause mortality (HR 1.43, 95% CI 1.07, 1.92). Time-varying models showed analogous increased risk in those who inconsistently slept ≥9 h/night (all P < 0.05), but not in those who consistently slept ≥9 h/night.

Conclusions

Consistent long or short sleep, which may reflect inter-individual variability in the need for sleep, does not appear to influence prognosis among early-stage breast cancer survivors.

     

Development of mammary hyperplasia,dysplasia, and invasive ductal carcinoma in transgenic mice expressing the 8p11 amplicon oncogene NSD3

Purpose

Tobacco smoking is a risk factor in several cancers, yet its roles as a putative etiologic exposure or poor prognostic factor in breast cancer are less clear. Altered DNA methylation contributes to breast cancer development and may provide a mechanistic link between smoking and gene expression changes leading to cancer development or progression.

Methods

Using a cancer-focused array, we examined methylation at 933 CpGs in 517 invasive breast tumors in the Carolina Breast Cancer Study to determine whether methylation patterns differ by exposure to tobacco smoke. Multivariable generalized linear regression models were used to compare tumor methylation profiles between smokers and never smokers, overall, or stratified on hormone receptor (HR) status.

Results

Modest differences in CpG methylation were detected at p < 0.05 in breast tumors from current or ever smokers compared with never smokers. In stratified analyses, HR- tumors from smokers exhibited primarily hypomethylation compared with tumors from never smokers; hypomethylation was similarly detected within the more homogeneous basal-like subtype. Most current smoking-associated CpG loci exhibited methylation levels in former smokers that were intermediate between those in current and never smokers and exhibited progressive changes in methylation with increasing duration of smoking. Among former smokers, restoration of methylation toward baseline (never smoking) levels was observed with increasing time since quitting. Moreover, smoking-related hypermethylation was stronger in HR+ breast tumors from blacks than in whites.

Conclusions

Our results suggest that breast tumor methylation patterns differ with tobacco smoke exposure; however, additional studies are needed to confirm these findings.

     

Health-related behaviors and mortality outcomes in women diagnosed with ductal carcinoma in situ

Purpose

Women diagnosed with ductal carcinoma in situ (DCIS) of the breast are at greater risk of dying from cardiovascular disease and other causes than from breast cancer, yet associations between health-related behaviors and mortality outcomes after DCIS have not been well studied.

Methods

We examined the association of body mass index, physical activity, alcohol consumption, and smoking with mortality among 1925 women with DCIS in the Wisconsin In Situ Cohort study. Behaviors were self-reported through baseline interviews and up to three follow-up questionnaires. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality after DCIS, with adjustment for patient sociodemographic, comorbidity, and treatment factors.

Results

Over a mean of 6.7 years of follow-up, 196 deaths occurred. All-cause mortality was elevated among women who were current smokers 1 year prior to diagnosis (HR?=?2.17 [95% CI 1.48, 3.18] vs. never smokers) and reduced among women with greater physical activity levels prior to diagnosis (HR?=?0.55 [95% CI: 0.35, 0.87] for ≥5 h per week vs. no activity). Moderate levels of post-diagnosis physical activity were associated with reduced all-cause mortality (HR?=?0.31 [95% CI 0.14, 0.68] for 2–5 h per week vs. no activity). Cancer-specific mortality was elevated among smokers and cardiovascular disease mortality decreased with increasing physical activity levels.

Conclusions

There are numerous associations between health-related behaviors and mortality outcomes after a DCIS diagnosis.

Implications for cancer survivors

Women diagnosed with DCIS should be aware that their health-related behaviors are associated with mortality outcomes.

     

Contribution of clinical and socioeconomic factors to differences in breast cancer subtype and mortality between Hispanic and non-Hispanic white women

Purpose

To assess tumor subtype distribution and the relative contribution of clinical and sociodemographic factors on breast cancer survival between Hispanic and non-Hispanic whites (NHWs).

Methods

We analyzed data from the California Cancer Registry, which included 29,626 Hispanic and 99,862 NHW female invasive breast cancer cases diagnosed from 2004 to 2014. Logistic regression was used to assess ethnic differences in tumor subtype, and Cox proportional hazard modeling to assess differences in breast cancer survival.

Results

Hispanics compared to NHWs had higher odds of having triple-negative (OR = 1.29; 95% CI 1.23–1.35) and HER2-overexpressing tumors (OR = 1.19; 95% CI 1.14–1.25 [HR?] and OR = 1.39; 95% CI 1.31–1.48 [HR+]). In adjusted models, Hispanic women had a higher risk of breast cancer mortality than NHW women (mortality rate ratio [MRR] = 1.24; 95% CI 1.19–1.28). Clinical factors accounted for most of the mortality difference (MRR = 1.05; 95% CI 1.01–1.09); however, neighborhood socioeconomic status (SES) and health insurance together accounted for all of the mortality difference (MRR = 1.01; 95% CI 0.97–1.05).

Conclusions

Addressing SES disparities, including increasing access to health care, may be critical to overcoming poorer breast cancer outcomes in Hispanics.

     

Pre-diagnostic aspirin use and mortality after breast cancer

Background

Whether aspirin or other nonsteroidal anti-inflammation drug (NSAID) use is associated with mortality following breast cancer remains unclear. Consideration of use patterns and interaction with obesity may help to clarify the inconsistent results.

Methods

Pre-diagnosis NSAID use, weight, and height were assessed?~?3 months after diagnosis through in-person interviews with a population-based cohort of 1,442 women with first primary breast cancer. Vital status was determined through the national death index after ~?18 years of follow-up (N?=?237/597 breast cancer-specific/all-cause deaths). We used Cox proportional hazards regression to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Multiplicative interaction by body mass index (BMI) was evaluated using the likelihood ratio test.

Results

Ever aspirin use was inversely associated with breast cancer-specific mortality (HR 0.87, 95% CI 0.59–1.29), but positively associated with all-cause mortality (HR 1.21, 95% CI 0.99–1.48); the CIs included the null values. The HRs, however, were more pronounced for the highest level of duration, frequency, regularity, and timing for all-cause, but not breast cancer-specific mortality. Interactions with BMI revealed no significant heterogeneity (p_interaction = 0.37 and p_interaction = 0.36, respectively).

Conclusion

Pre-diagnosis aspirin use was not strongly associated with mortality following breast cancer. The all-cause mortality associations, however, were slightly stronger when we considered patterns of use.

     

Occurrence and outcome of de novo metastatic breast cancer by subtype in a large,diverse population

Purpose

To examine the occurrence and outcomes of de novo metastatic (Stage IV) breast cancer, particularly with respect to tumor HER2 expression.

Methods

We studied all 6,268 de novo metastatic breast cancer cases diagnosed from 1 January 2005 to 31 December 2011 and reported to the California Cancer Registry. Molecular subtypes were classified according to HER2 and hormone receptor (HR, including estrogen and/or progesterone receptor) expression. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) of Stage IV versus Stage I–III breast cancer; Cox proportional hazards regression was used to assess relative hazard (RH) of mortality.

Results

Five percent of invasive breast cancer was metastatic at diagnosis. Compared to patients with earlier stage disease, patients with de novo metastatic disease were significantly more likely to have HER2+ tumors (HR+/HER2+: OR 1.29, 95 % CI 1.17–1.42; HR?/HER2+: OR 1.40, 95 %CI 1.25–1.57, vs. HR+/HER2?). Median survival improved over time, but varied substantially across race/ethnicity (Asians: 34 months; African Americans: 6 months), neighborhood socioeconomic status (SES) (highest: 34 months, lowest: 20 months), and molecular subtype (HR+/HER2+: 45 months; triple negative: 12 months). In a multivariable model, triple negative (RH 2.85, 95 % CI 2.50–3.24) and HR?/HER2+ (RH 1.60, 95 % CI 1.37–1.87) had worse, while HR+/HER2+ had similar, risk of all-cause death compared to HR+/HER2? breast cancer.

Conclusions

De novo metastatic breast cancer was more likely to be HER2+. Among metastatic tumors, those that were HER2+ had better survival than other subtypes.

     

Inverse relationship between Ki67 and survival in early luminal breast cancer: confirmation in a multivariate analysis

Introduction

Ki67 is a prognostic marker in early breast cancer, but its real usefulness remains controversial. The standard cut-off values for Ki67 have not been universally accepted and different values may be used depending on the type of biopsy (fine needle biopsy versus surgical specimen biopsy). The objective of this study was to evaluate the prognostic significance of Ki67 and to determine the most accurate prognostic cut-off.

Materials and methods

495 tissue samples from patients with luminal tumours who underwent breast surgery between 2005 and 2011 were collected from the Department of Pathology at Hospital de la Santa Creu i Sant Pau, Barcelona. Patients with stage IV, HER2-positive tumours or triple-negative breast carcinoma were excluded from the study. Pathology data including tumour grading and ki67 percentage were obtained retrospectively from clinical records. In all cases, the percentage of ki67 was evaluated in fine needle biopsies.

Results

In the multivariate analysis, Ki67 as a continuous variable was associated with poor overall survival (OS) and cancer-specific survival (CSS) (OS p = 0.0001, HR 1.037, CI 1.014–1.059; CSS p = 0.0001, HR 1.063, CI 1.031–1.096) (Cox regression model). CSS was poor when associated with a KI67 cut-off point >14% (p = 0.013, HR 14.85; CI 1.074–120.53) (Cox regression model). Disease-free survival (DFS) was not associated with Ki67

Conclusions

Prognosis of luminal breast carcinoma can be predicted using Ki67 as a continuous variable and a standard cut-off value of 14%. Information about the specimen type used to determine ki67 should be recorded in the pathological report.

     

Breast cancer and exposure to tobacco smoke during potential windows of susceptibility

Purpose

An association between smoking and breast cancer is unresolved, although a higher risk from exposure during windows of susceptibility has been proposed. The objective of this prospective study was to evaluate the association between tobacco smoke and breast cancer with a focus on timing of exposure, especially during early life.

Methods

Sister study participants (n = 50,884) aged 35–74 were enrolled from 2003 to 2009. Women in the United States and Puerto Rico were eligible if they were breast cancer-free but had a sister with breast cancer. Participants completed questionnaires on smoking and environmental tobacco smoke (ETS) exposure. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for breast cancer risk.

Results

During follow-up (mean = 6.4 years), 1,843 invasive breast cancers were diagnosed. Neither active smoking nor adult ETS was associated with breast cancer risk. However, never smoking women exposed to ETS throughout their childhood had a 17% higher risk of breast cancer (95% CI 1.00–1.36) relative to those with no exposure. In utero ETS exposure was also associated with breast cancer (HR = 1.16, 95% CI 1.01–1.32) and the HR was most elevated for women born in earlier birth cohorts (<1940, HR = 1.44, 95% CI 1.02–2.02; 1940–1949, HR = 1.28, 95% CI 1.01–1.62).

Conclusion

In utero ETS and ETS exposure during childhood and adolescence were associated with increased risk of breast cancer and associations varied by birth cohort.

     

Estrogen receptor quantitative measures and breast cancer survival

Purpose

While the estrogen receptor (ER) is the single most widely used biomarker to evaluate breast cancer outcomes, aspects of ER marker biology remain poorly understood. We sought to determine whether quantitative measures of ER, such as protein expression and intensity, were associated with survival, or with survival disparities experienced by Hispanic women.

Methods

A case-cohort study included a 15% random sample of invasive breast cancer cases diagnosed from 1997 to 2009 in six New Mexico counties and all deaths due to breast cancer-related causes. Pathology reports and tissue microarrays served as sources of ER information. Analyses were restricted to women with ≥1% ER immunohistochemical staining. Hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer death were estimated using Cox proportional hazards models.

Results

Included women represented 4336 ER+ breast cancer cases and 448 deaths. Median follow-up was 93 months. ER percent expression was not associated with breast cancer survival after adjustment for standard prognostic factors (p trend = 0.76). ER intensity remained a strong and independent risk factor for breast cancer survival in multivariate analyses: Women whose tumors expressed ER at intensity = 2 (HR 0.6; 95% CI 0.4–1.0) or 3 (HR 0.5; 95% CI 0.2–0.9) had a reduced risk of breast cancer mortality, compared to ER intensity = 1 (p trend = 0.02). Neither ER protein expression nor intensity influenced Hispanic survival disparities.

Conclusions

Estrogen receptor percent positive staining is not independently related to breast cancer survival after adjustment for other survival-related factors. ER intensity, in contrast, demonstrates promise for prognostic utility.

     

Active smoking and risk of Luminal and Basal-like breast cancer subtypes in the Carolina Breast Cancer Study

Purpose

Growing evidence suggests an association between active cigarette smoking and increased breast cancer risk. However, the weak magnitude of association and conflicting results have yielded uncertainty and it is unknown whether associations differ by breast cancer subtype.

Methods

Using population-based case–control data from phases I and II of the Carolina Breast Cancer Study, we examined associations between self-reported measures of smoking and risk of Luminal and Basal-like breast cancers. We used logistic regression models to estimate case–control odds ratios (OR) and 95 % confidence intervals (CI).

Results

Ever smoking (current and former) was associated with a weakly increased risk of Luminal breast cancer (OR 1.12, 95 % CI 0.92–1.36) and was not associated with risk of Basal-like breast cancer (OR 0.96, 95 % CI 0.69–1.32). Similarly, smoking duration of more than 20 years was associated with increased risk of Luminal (OR 1.51, 95 % CI 1.19–1.93), but not Basal-like breast cancer (OR 0.90, 95 % CI 0.57–1.43). When stratified by race, elevated odds ratios between smoking and Luminal breast cancer risk were found among black women across multiple exposure measures (ever smoking, duration, and dose); conversely, among white women odds ratios were attenuated or null.

Conclusions

Results from our study demonstrate a positive association between smoking and Luminal breast cancer risk, particularly among black women and women with long smoking histories. Addressing breast cancer heterogeneity in studies of smoking and breast cancer risk may elucidate associations masked in prior studies.

     

Cigarette smoking and the association with serous ovarian cancer in African American women: African American Cancer Epidemiology Study (AACES)

Background

Smoking is a risk factor for mucinous ovarian cancer (OvCa) in Caucasians. Whether a similar association exists in African Americans (AA) is unknown.

Methods

We conducted a population-based case–control study of incident OvCa in AA women across 11 geographic locations in the US. A structured telephone interview asked about smoking, demographic, health, and lifestyle factors. Odds ratios and 95% confidence intervals (OR, 95% CI) were estimated from 613 cases and 752 controls using unconditional logistic regression in multivariable adjusted models.

Results

Associations were greater in magnitude for serous OvCa than for all OvCa combined. Compared to never smokers, increased risk for serous OvCa was observed for lifetime ever smokers (1.46, 1.11–1.92), former smokers who quit within 0–2 years of diagnosis (5.48, 3.04–9.86), and for total pack-years smoked among lifetime ever smokers (0–5 pack-years: 1.79, 1.23–2.59; >5–20 pack-years: 1.52, 1.05–2.18; >20 pack-years: 0.98, 0.61–1.56); however, we observed no dose–response relationship with increasing duration or consumption and no significant associations among current smokers. Smoking was not significantly associated with mucinous OvCa. Associations for all OvCa combined were consistently elevated among former smokers. The proportion of ever smokers who quit within 0–2 years was greater among cases (23%) than controls (7%).

Conclusions

Cigarette smoking may be associated with serous OvCa among AA, which differs from associations reported among Caucasians. Exposure misclassification or reverse causality may partially explain the absence of increased risk among current smokers and lack of dose–response associations. Better characterization of smoking patterns is needed in this understudied population.

     

Association between carotenoids and outcome of cervical intraepithelial neoplasia: a prospective cohort study

Background

It has been suggested that micronutrients such as alpha-tocopherol, retinol, lutein, cryptoxanthin, lycopene, and alpha- and beta-carotene may help in the prevention of cervical cancer. Our aim was to investigate whether serum concentrations and/or dietary intake of micronutrients influence the regression or progression of low-grade cervical abnormalities.

Methods

In a prospective cohort study of 391 patients with cervical intraepithelial neoplasia (CIN) grade 1–2 lesions, we measured serum micronutrient concentrations in addition to a self-administered questionnaire about dietary intake. We evaluated the hazard ratio (HR) adjusted for CIN grade, human papillomavirus genotype, total energy intake and smoking status.

Results

In non-smoking regression subjects, regression was significantly associated with serum levels of zeaxanthin/lutein (HR 1.25, 0.78–2.01, p = 0.024). This benefit was abolished in current smokers. Regression was inhibited by high serum levels of alpha-tocopherol in smokers (p = 0.042). In progression subjects, a significant protective effect against progression to CIN3 was observed in individuals with a medium level of serum beta-carotene [HR 0.28, 95 % confidence interval (CI) 0.11–0.71, p = 0.007), although any protective effect from a higher level of serum beta-carotene was weaker or abolished (HR 0.52, 95 % CI 0.24–1.13, p = 0.098). Increasing beta-carotene intake did not show a protective effect (HR 2.30, 95 % CI 0.97–5.42, p = 0.058).

Conclusions

Measurements of serum levels of carotenoids suggest that regression is modulated by smoking status. Maintaining a medium serum level of beta-carotene has a protective effect for progression; however, carotene intake is not correlated with serum levels of carotenoids.

     

Racial differences in the effects of comorbidity on breast cancer-specific survival

Purpose

In an effort to explain racial disparities in breast cancer survival, this study aimed to investigate how comorbidity affects breast cancer-specific mortality by race.

Methods

A retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results—Medicare linked data including 68,090 women 66+ years, who were diagnosed with stage I–III breast cancer in the United States from 1994 to 2004. Hospital and outpatient claims from the year prior to breast cancer diagnosis were used to identify comorbid conditions and patients were followed for survival through 2010.

Results

Competing risk survival analysis failed to demonstrate any negative comorbidity effects on breast cancer-specific survival for black women. An increased breast cancer-specific mortality hazard was observed for white women who had diabetes without complication relative to white women without this condition after adjusting for age and year of diagnosis (hazard ratio: 1.22, 95% confidence interval 1.13, 1.30). The Cochran–Armitage Test showed diabetes was associated with a later stage of diagnosis (p < 0.01) and a more aggressive tumor grade (p < 0.01) among white women in the study population.

Conclusion

Race specific comorbidity effects do not explain breast cancer-specific survival disparities. However, the relationship between diabetes and breast cancer, including the role of aggressive tumor characteristics, warrants special attention.

     

Obesity and mortality after locoregional breast cancer diagnosis

Purpose

Higher mortality after a breast cancer diagnosis has been observed among women who are obese. We investigated the relationships between body mass index (BMI) and all-cause or breast cancer-specific mortality after a diagnosis of locoregional breast cancer.

Methods

Women diagnosed in 2004 with AJCC Stage I, II, or III breast cancer (n?=?5394) were identified from a population-based National Program of Cancer Registries (NPCR) patterns of care study (POC-BP) drawing from registries in seven U.S. states. Differences in overall and breast cancer-specific mortality were investigated using Cox proportional hazards regression models adjusting for demographic and clinical covariates, including age- and stage-based subgroup analyses.

Results

In women 70 or older, higher BMI was associated with lower overall mortality (HR for a 5 kg/m² difference in BMI?=?0.85, 95% CI 0.75–0.95). There was no significant association between BMI and overall mortality for women under 70. BMI was not associated with breast cancer death in the full sample, but among women with Stage I disease; those in the highest BMI category had significantly higher breast cancer mortality (HR for BMI?≥?35 kg/m² vs. 18.5–24.9 kg/m²?=?4.74, 95% CI 1.78–12.59).

Conclusions

Contrary to our hypothesis, greater BMI was not associated with higher overall mortality. Among older women, BMI was inversely related to overall mortality, with a null association among younger women. Higher BMI was associated with breast cancer mortality among women with Stage I disease, but not among women with more advanced disease.

     

Smoking status,usual adult occupation,and risk of recurrent urothelial bladder carcinoma: data from The Cancer Genome Atlas (TCGA) Project

Purpose

Tobacco smoking and occupational exposures are the leading risk factors for developing urothelial bladder carcinoma (UBC), yet little is known about the contribution of these two factors to risk of UBC recurrence. We evaluated whether smoking status and usual adult occupation are associated with time to UBC recurrence for 406 patients with muscle-invasive bladder cancer submitted to The Cancer Genome Atlas (TCGA) project.

Methods

Kaplan–Meier and Cox proportional hazard methods were used to assess the association between smoking status, employment in a high-risk occupation for bladder cancer, occupational diesel exhaust exposure, and 2010 Standard Occupational Classification group and time to UBC recurrence.

Results

Data on time to recurrence were available for 358 patients over a median follow-up time of 15 months. Of these, 133 (37.2%) experienced a recurrence. Current smokers who smoked for more than 40 pack-years had an increased risk of recurrence compared to never smokers (HR 2.1, 95% CI 1.1, 4.1). Additionally, employment in a high-risk occupation was associated with a shorter time to recurrence (log-rank p = 0.005). We found an increased risk of recurrence for those employed in occupations with probable diesel exhaust exposure (HR 1.8, 95% CI 1.1, 3.0) and for those employed in production occupations (HR 2.0, 95% CI 1.1, 3.6).

Conclusions

These findings suggest smoking status impacts risk of UBC recurrence, although several previous studies provided equivocal evidence regarding this association. In addition to the known causal relationship between occupational exposure and bladder cancer risk, our study suggests that occupation may also be related to increased risk of recurrence.