Despite limited evidence on the association of vitamin D with outcomes in breast cancer survivors, some clinicians advise breast cancer patients to use vitamin D supplements. More evidence is needed to inform these recommendations.
In the Health, Eating, Activity and Lifestyle Study, we examined associations of post-treatment serum concentrations of 25-hydroxyvitamin D (25(OH)D) on overall and breast-cancer-specific mortality in 585 breast cancer survivors from western Washington State, New Mexico, and Los Angeles County. 25(OH)D was measured in stored blood collected 2 years post-enrollment. Outcomes were ascertained from the Surveillance, Epidemiology, and End Results registries and medical records. Cox proportional hazards models were fit to assess associations of serum 25(OH)D with overall and breast-cancer-specific mortality.
After a median follow-up of 9.2 years; 110 women died, including 48 from breast cancer. Standard cut points classified 211 (31.6%) women as serum 25(OH)D deficient (<20 ng/mL), 189 (32.2%) as insufficient (20–30 ng/mL), and 185 (36.2%) as sufficient (>30 ng/mL). Compared to women with deficient 25(OH)D, those in the sufficient ranges had a decreased risk of overall mortality (age-adjusted HR=0.58; 95%CI 0.36–0.96); however multivariate adjustments attenuated the association (HR=0.90; 95%CI 0.50–1.61). No association was found between serum 25(OH)D and breast-cancer-specific mortality (sufficient: HR=1.21; 95%CI 0.52–2.80) in multivariate models.
In this breast cancer cohort, higher serum 25(OH)D may be associated with improved survival, but results were not statistically significant and must be interpreted with caution. The potential prognostic effect of vitamin D from diet, supplements or both should be evaluated in future larger studies with additional endpoints from breast cancer patients.
25-hydroxyvitamin D; overall mortality; breast-cancer-specific mortality; vitamin D
Case-control and cohort studies are almost always complicated by nonrandom exposure allocation, which must be minimized in the design and analysis phases. Tubal sterilization is a common gynecological procedure that may be associated with other reproductive organ surgeries, which in turn may be associated with breast cancer risk. In this issue of the Journal, Gaudet et al. (Am J Epidemiol. 2013;177(6):492–499) argue successfully that tubal sterilization is unassociated with breast cancer risk. Scrutiny of the heterogeneous studies included in their meta-analysis underscores the role of confounding and effect modification in observational epidemiologic studies. Specifically, tubal sterilization is unassociated with breast cancer risk, but either oophorectomy or hysterectomy, or both, and the timing of these procedures warrant careful consideration in the design, analysis, and interpretation of observational research on reproductive factors.
breast neoplasms; case-control studies; cohort studies; hysterectomy; meta-analysis; oophorectomy; tubal sterilization
Although physical activity modulates the hypothalamic-ovarian-pituitary axis, the few studies investigating whether physical activity is associated with age at natural menopause have had mixed results. We set out to determine whether physical activity is associated with the timing of natural menopause in a large cohort of California women, overall, and by smoking history.
We investigated the association between long-term physical activity (hours/week/year) and age at natural menopause among 97,945 women in the California Teachers Study. Multivariable Cox proportional hazards regression methods were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). The impact of cigarette smoking (never smoker, former-light smoker, former-heavy smoker, current-light smoker, current-heavy smoker) as an effect modifier was evaluated.
In a multivariable model adjusting for body mass index at age 18, age at menarche, race/ethnicity, and age at first full-term pregnancy, increased physical activity was statistically significantly associated with older age at natural menopause (ptrend=0.005). Higher body mass index at age 18 (ptrend=0.0003) and older age at menarche (ptrend=0.0003) were also associated with older age at natural menopause. Hispanic ethnicity (vs. non-Hispanic whites, HR 1.17, 95% CI 1.09–1.26), current smokers (vs. never smokers, HR 1.68, 95% CI 1.60–1.75 for current-light smokers; HR 1.38, 95% CI 1.33–1.44 for current-heavy smokers) and older age at first full-term pregnancy (HR≥29, 2+ full-term pregnancies vs. <29, 2+ full-term pregnancies 1.10, 95% CI 1.06–1.14) were associated with earlier age at natural menopause. Upon stratification by smoking history, increased physical activity was statistically significantly associated with older natural menopause among heavy smokers only (HRHighest vs. Lowest quartile 0.88, 95% CI 0.81–0.97, ptrend=0.02 for former-heavy smokers; HRHighest vs. Lowest quartile 0.89, 95% CI 0.80–0.99, ptrend=0.04 for current-heavy smokers).
Age at natural menopause is a complex trait; the determinants of age at natural menopause, including physical activity, may differ by smoking status.
Physical activity; smoking status; age at natural menopause; reproductive factors; cohort studies
Elevated circulating insulin-like growth factor-1 (IGF-1), a breast epithelial cell mitogen, is associated with breast cancer development. However, its association with breast cancer survival is not established. Circulating concentrations of IGF-1 are controlled via binding proteins, including IGF Binding Protein-3 (IGFBP-3), that may modulate the association of IGF1 with breast-cancer outcomes.
We measured IGF-1 and IGFBP-3 concentrations in serum from 600 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between IGF-1 and IGFBP-3, and as a ratio, modeled using quintile cut-points, with risk of breast cancer-specific (n=42 deaths) and all-cause mortality (n=87 deaths) using Cox proportional hazards models. In models adjusted for body mass index, ethnicity, tamoxifen use at time of blood draw, treatment received at diagnosis, and IGFBP-3, women in the highest quintile of IGF-1 level had an increased risk of all-cause mortality (Hazard Ratio (HR)=3.10 95% CI 1.21-7.93, p=0.02), although no dose-response association was evident. The IGF-1/IGFBP-3 ratio, an indicator of free IGF-I levels, was significantly associated with increasing risk of all-cause mortality (HR=2.83 95% CI 1.25-6.36 Ptrend=0.01, upper vs. lower quintile) in a fully adjusted model.
In conclusion, high serum levels of IGF-1 and the IGF-1/IGFBP-3 ratio were associated with increased risk of all-cause mortality in women with breast cancer. These results need to be confirmed in larger breast cancer survivor cohorts.
IGF-1; IGFBP-3; breast cancer survival; mortality
Many cancer survivors experience declines in health-related quality of life (HRQOL) and increases in fatigue as a result of cancer and its treatment. Exercise is linked to improvements in these outcomes, but little is known about the role of sedentary behavior. In a large, ethnically-diverse cohort of breast cancer survivors, we examined the relationship between sedentary time, HRQOL, and fatigue, and examined if that relationship differed by recreational moderate-vigorous physical activity (MVPA) level.
Participants were 710 women diagnosed with stage 0-IIIA breast cancer in the Health, Eating, Activity, and Lifestyle Study. Women completed questionnaires at approximately 30-months postdiagnosis (sedentary time; recreational MVPA) and 41-months postdiagnosis (HRQOL; fatigue). In multivariate models, we regressed these outcomes linearly on quartiles of daily sedentary time, and a variable jointly reflecting sedentary time quartiles and MVPA categories (0; > and <; ≥9 MET-hrs/wk).
Sedentary time was not independently related to subscales or summary scores of HRQOL or fatigue. Additionally, comparisons of women with high vs. low (Q4:Q1) sedentary time by MVPA level did not result in significant differences in HRQOL or fatigue.
In this breast cancer survivor cohort, self-reported sedentary time was not associated with HRQOL or fatigue, 3.5 years postdiagnosis.
health behavior; survivorship; epidemiology
Reconstruction rates after mastectomy have been reported to range from 25–40 %; however, most studies have focused on patients treated in an inpatient setting. We sought to determine the utilization of outpatient mastectomy and use of breast reconstruction in Southern California.
Postmastectomy reconstruction rates were determined from the California Office of Statewide Health Planning and Development database from 2006–2009 using CPT codes and similarly from an inpatient database using ICD-9 codes. Reconstruction rates were compared between the inpatient and outpatient setting. For the outpatient setting, univariate and multivariate odds ratios with 95 % confidence intervals were estimated for relative odds of immediate reconstruction versus mastectomy alone.
The percentage of patients undergoing outpatient mastectomy ranged from 20.4 to 23.9 % of the total number of all patients undergoing mastectomy. Whereas immediate inpatient reconstruction increased from 29.2 to 41.6 % (overall rate 35.5 %), the proportion of outpatients undergoing reconstruction only increased from 7.7 to 10.3 % (overall rate 9.1 %). Similar to the inpatient setting, in multivariate analysis, age, insurance status, race/ethnicity, and type of hospital were significantly associated with the use of reconstruction in the outpatient setting.
A substantial number of patients undergo outpatient mastectomy with low rates of reconstruction. Although the choice of an outpatient mastectomy may certainly represent a selection bias for those not choosing reconstruction, an increase in the use of outpatient mastectomy may result in decreases in the use of post-mastectomy reconstruction.
To measure the association between use of estrogenic botanical supplements and serum sex hormones in postmenopausal breast cancer survivors.
502 postmenopausal women were queried 2-3 years after breast cancer diagnosis about their use of botanical supplements, and supplements were categorized according to their estrogenic properties. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS) and sex hormone-binding globulin. Adjusted means of the serum hormones were calculated by use of estrogenic supplements.
Women reporting use of any estrogenic botanical supplement had significantly lower levels of estrone (20.8 v 23.6 pg/mL), estradiol (12.8 v 14.7 pg/mL), free estradiol (0.29 v 0.35 pg/mL), and DHEAS (47.7 v 56.2 ug/dL) compared to women reporting no use.
Data from this cross-sectional study suggest the use of estrogenic botanical supplements may be associated with sex hormone concentrations in breast cancer survivors. Considering the high use of these supplements among breast cancer patients, further research is needed to clarify the relative estrogenicity/antiestrogenicity of these compounds and their relation with prognosis.
Sleep duration among breast cancer survivors correlates with fatigue, depression, and health-related quality of life (HRQOL); however, this has not been studied longitudinally. This study investigated patterns of sleep duration change across the early breast cancer survivorship period, their demographic and clinical predictors, and their relationships with subsequent cancer-related symptoms and HRQOL.
Breast cancer survivors (n=572), were assessed 6 months post-diagnosis (current sleep & retrospective reports of pre-diagnosis sleep), 30 months post-diagnosis (sleep), and 39 months post-diagnosis (symptoms, HRQOL). Sleep duration change was determined by examining sleep at each time point in relation to published norms. Analysis of variance and logistic regression models tested demographic and clinical differences between the sleep change groups; linear regression models tested differences in symptoms and HRQOL.
Half of the survivors reported no sleep duration change over time; however, 25% reported sleep changes indicating a temporary (5.6%), late-occurring (14%), or sustained (5.9%) change. Survivors reporting sustained or temporary sleep changes were more likely to have been treated with chemotherapy (OR=2.62, p<.001) or gained weight after diagnosis (OR=1.82, p=.04) than those with no sleep change. Sustained sleep changes were related to greater subsequent severity, affective, and sensory aspects of fatigue (βs=2.0, 2.3, 1.8; all p <.0001) and lower vitality (β=−10.8, p=.005).
Survivors treated with chemotherapy and those who gain weight after diagnosis may have increased risk for sustained sleep duration changes, which may increase their fatigue. These results point to the need for routine assessment of sleep as part of survivorship care.
Breast Cancer; Survivors; Long-term Effects; Sleep; Quality of Life
Nutritional status is known to alter immune function, a suspected risk factor for non-Hodgkin lymphoma (NHL). To investigate whether long-term over, or under, nutrition is associated with NHL self-reported anthropometric data on weight and height from over 10000 cases of NHL and 16000 controls were pooled across 18 case-control studies identified through the International Lymphoma Epidemiology Consortium. Study-specific odds ratios (OR) were estimated using logistic regression and combined using a random-effects model. Severe obesity, defined as BMI of 40 kg m−2 or more, was not associated with NHL overall (pooled OR=1.00, 95% confidence interval (CI) 0.70–1.41) or the majority of NHL subtypes. An excess was however observed for diffuse large B-cell lymphoma (pooled OR=1.80, 95% CI 1.24–2.62), although not all study-specific ORs were raised. Among the overweight (BMI 25–29.9 kg m−2) and obese (BMI 30–39.9 kg m−2), associations were elevated in some studies and decreased in others, while no association was observed among the underweight (BMI<18.5 kg m−2). There was little suggestion of increasing ORs for NHL or its subtypes with every 5 kg m−2 rise in BMI above 18.5 kg m−2. BMI components height and weight were also examined, and the tallest men, but not women, were at marginally increased risk (pooled OR=1.19, 95% CI 1.06–1.34). In summary, whilst we conclude that there is no evidence to support the hypothesis that obesity is a determinant of all types of NHL combined, the association between severe obesity and diffuse large B-cell lymphoma may warrant further investigation.
non-Hodgkin lymphoma; lymphoma; body mass index; weight; height; epidemiology
Estrogen receptor–negative (ER−) breast cancer has few known
or modifiable risk factors. Because ER− tumors account for only 15% to
20% of breast cancers, large pooled analyses are necessary to evaluate precisely the
suspected inverse association between fruit and vegetable intake and risk of
ER− breast cancer.
Among 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19
869 estrogen receptor positive (ER+) and 4821 ER−
breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95%
confidence intervals (CIs) using Cox proportional hazards regression analyses and then
combined them using a random-effects model. All statistical tests were two-sided.
Total fruit and vegetable intake was statistically significantly inversely associated
with risk of ER− breast cancer but not with risk of breast cancer
overall or of ER+ tumors. The inverse association for
ER− tumors was observed primarily for vegetable consumption. The
pooled relative risks comparing the highest vs lowest quintile of total vegetable
consumption were 0.82 (95% CI = 0.74 to 0.90) for ER− breast
cancer and 1.04 (95% CI = 0.97 to 1.11) for ER+ breast cancer
common-effects by ER status < .001). Total fruit consumption was
non-statistically significantly associated with risk of ER− breast
cancer (pooled multivariable RR comparing the highest vs lowest quintile = 0.94,
95% CI = 0.85 to 1.04).
We observed no association between total fruit and vegetable intake and risk of overall
breast cancer. However, vegetable consumption was inversely associated with risk of
ER− breast cancer in our large pooled analyses.
There is a paucity of data on familial risk of developing esophageal adenocarcinoma, gastric cardia adenocarcinoma and distal gastric adenocarcinoma from population-based studies.
A population-based case–control study of newly diagnosed gastroesophageal adenocarcinoma was conducted in Los Angeles County. This analysis included data of case-patients whom we were able to interview directly (147 patients with esophageal adenocarcinoma, 182 with gastric cardia adenocarcinoma, and 285 with distal gastric adenocarcinoma) and 1,309 control participants. Multivariate polytomous logistic regression was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the three cancer types.
Risk of esophageal adenocarcinoma was positively associated with a family history of prostate cancer (OR = 2.84; 95% CI = 1.50-5.36) and a family history of hiatal hernia (OR = 2.04; 95% CI = 1.12-3.71). Risk of gastric cardia adenocarcinoma was strongly associated with a family history of esophageal cancer (OR = 5.18; 95% CI = 1.23-21.79) and a family history of hiatal hernia (OR = 2.31; 95% CI = 1.37-3.91). Risk of distal gastric adenocarcinoma was positively associated with a family history of gastric cancer (OR = 2.15; 95% CI = 1.18-3.91), particularly early-onset (before age 50) gastric cancer (OR = 2.82; 95% CI = 1.11-7.15).
This study provides evidence that family history of hiatal hernia is a risk factor for esophageal adenocarcinoma and gastric cardia adenocarcinoma and that cancer in specific sites is associated with risk of esophageal adenocarcinoma, gastric cardia adenocarcinoma, and distal gastric adenocarcinoma. It is important to determine the extent to which shared environmental and genetic factors explain these familial associations.
Hiatal hernia; Family history; Esophageal adenocarcinoma, Gastric cardia; Distal gastric cancer
Little is known about the relationship between physical activity and thyroid cancer risk, and few cohort data on this association exist. Thus, the present study aimed to prospectively examine long-term activity and risk of papillary thyroid cancer among women.
116,939 women in the California Teachers Study, aged 22 to 79 years with no history of thyroid cancer at cohort entry, were followed from 1995-1996 through 2009; 275 were diagnosed with invasive papillary thyroid cancer. Cox proportional-hazards regression provided relative risk (RR) estimates and 95% confidence intervals (CI) for associations between thyroid cancer and combined strenuous and moderate recreational physical activity both in the long-term (high school through age 54 years or current age if younger than 54 years) and recently (during the three years prior to joining the cohort).
Overall, women whose long-term recreational physical activity averaged at least 5.5 MET-hours/week (i.e. were active) had a non-significant 23% lower risk of papillary thyroid cancer than inactive women (RR=0.77, 95% CI: 0.57, 1.04). RR estimates were stronger among normal weight or underweight women (body mass index, BMI<25.0 kg/m2, trend p=0.03) than among overweight or obese women (trend p=0.35; homogeneity-of-trends p=0.03). A similar pattern of risk was observed for recent activity (BMI<25 kg/m2, trend p=0.11; BMI≥25 kg/m2, trend p=0.16; homogeneity-of-trends p=0.04). Associations for long-term activity did not appear to be driven by activity in any particular life period (e.g. youth, adulthood).
Long-term physical activity may reduce papillary thyroid cancer risk among normal weight and underweight women.
Physical activity; thyroid cancer; cancer prevention; women; overweight/obesity; Body Mass Index
To fully characterize the risk of contralateral breast cancer (CBC) in patients with breast cancer with a family history who test negative for BRCA1 and BRCA2 mutations.
Patients and Methods
From our population-based case-control study comparing women with CBC to women with unilateral breast cancer (UBC), we selected women who tested negative for BRCA1 and BRCA2 mutations (594 patients with CBC/1,119 control patients with UBC). Rate ratios (RRs) and 95% CIs were estimated to examine the association between family history of breast cancer and risk of asynchronous CBC. Age- and family history–specific 10-year cumulative absolute risks of CBC were estimated.
Family history of breast cancer was associated with increased CBC risk; risk was highest among young women (< 45 years) with first-degree relatives affected at young ages (< 45 years; RR, 2.5; 95% CI, 1.1 to 5.3) or women with first-degree relatives with bilateral disease (RR, 3.6; 95% CI, 2.0 to 6.4). Women diagnosed with UBC before age 55 years with a first-degree family history of CBC had a 10-year risk of CBC of 15.6%.
Young women with breast cancer who have a family history of breast cancer and who test negative for deleterious mutations in BRCA1 and BRCA2 are at significantly greater risk of CBC than other breast cancer survivors. This risk varies with diagnosis age, family history of CBC, and degree of relationship to an affected relative. Women with a first-degree family history of bilateral disease have risks of CBC similar to mutation carriers. This has important implications for the clinical management of patients with breast cancer with family history of the disease.
Endotoxin, a component of the outer membrane of gram-negative bacteria, elicits a strong innate and inflammatory immune response associated with secretion of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α). Because TNF-α polymorphisms that increase TNF-α production are associated with an increased risk of non-Hodgkin lymphoma (NHL), we hypothesized that increased levels of household endotoxin would be associated with an increased NHL risk.
We evaluated this association in the National Cancer Institute/Surveillance, Epidemiology and End Result (NCI/SEER) NHL multi-center population-based case-control study. Used vacuum cleaner bags were collected from participants during a home interview. Dust samples from the bags of 594 cases and 442 controls were analyzed for endotoxin (Endotoxin Unit [EU]/mg of dust) using the kinetic chromogenic Limulus amebocyte lysate assay. Multivariable logistic regression was used to estimate the effect of endotoxin on NHL risk adjusted for age, sex, race, education, study center, and farm exposure.
Endotoxin was not associated with NHL overall (odds ratio [OR] for highest quartile of endotoxin levels = 0.81, 95% confidence interval [CI]= 0.55,1.20; P for trend=0.35), or with diffuse large B-cell lymphoma (OR= 0.63, 95% CI= 0.34, 1.16; P= 0.31) or follicular lymphoma (OR= 0.1.07, 95% CI=0.61, 1.89; P=0.73) subtypes. Both working and living on a farm were associated with higher household endotoxin levels compared to never working (P=0.009) or living (P=0.01) on a farm. Excluding farmers from the analysis did not change the results.
We found no evidence of a role for household endotoxin in NHL etiology.
Endotoxin; Non-Hodgkin lymphoma; Epidemiology; Farming; Risk; Case-control
Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of > 1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10−6 and 10−5 in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3×10−6; rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5×10−5). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample.
GWAS; breast cancer; African ancestry; common genetic variation
Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10-5 in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10−8) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10–6) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10−9), and with both ER-positive (OR = 1.09; P = 1.5 × 10−5) and ER-negative (OR = 1.16, P = 2.5 × 10−7) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.
Evidence is inconsistent regarding whether dietary fat influences sex hormone concentrations. This issue is important for breast cancer survivors since clinical recommendations suggest maintaining low hormone levels primarily via pharmacologic agents. This study examines associations between dietary fat and circulating sex hormones among participants in the HEAL (Health, Eating, Activity and Lifestyle) Study, a cohort of breast cancer survivors (n=511). During a post-diagnosis interview, detailed data were collected on diet, physical activity, lifestyle habits, and medication use (including tamoxifen). Staff measured height and weight and collected fasting bloods. Multivariate linear regression modeled associations of dietary fat with serum sex hormones. Among women using tamoxifen, we observed modest inverse associations of dietary fat with estrone (p< 0.01), estradiol (p< 0.05), testosterone (p< 0.01), free testosterone (p< 0.01), and DHEA (p< 0.01) for higher vs. lower fat intake, but there was no evidence for a trend. Associations were consistent across measures (percent energy from fat, total, saturated and polyunsaturated fat) and modest effect modification was observed between fat intake and tamoxifen in relation to hormones. Among women not using tamoxifen, fat intake was not associated with hormone concentrations. Further work is needed to confirm the findings and to understand the clinical implications of these observations.
Diet; dietary fat; sex steroid hormones; estrogen; testosterone; postmenopausal breast cancer; tamoxifen
Body mass index (BMI), a known breast cancer risk factor, could influence breast risk through mechanistic pathways related to sex hormones, insulin resistance, chronic inflammation and altered levels of adipose derived hormones. Results from studies of the relationship between BMI and second primary breast cancer have been mixed. To explore the relationship between BMI and asynchronous contralateral breast cancer (CBC), we examined whether variants in genes related to obesity, weight and weight change are associated with CBC risk.
Variants in twenty genes (182 single nucleotide polymorphisms) involved in adipose tissue metabolism, energy balance, insulin resistance and inflammation, as well as those identified through genome-wide association studies of BMI and type II diabetes were evaluated. We examined the association between variants in these genes and the risk of CBC among Caucasian participants (643 cases with CBC and 1,271 controls with unilateral breast cancer) in the population-based Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study using conditional logistic regression.
After adjustment for multiple comparisons, no statistically significant associations between any variant and CBC risk were seen. Stratification by menopausal or estrogen receptor status did not alter these findings.
Among women with early onset disease who survive a first breast cancer diagnosis there was no association between variation in obesity-related genes and risk of CBC.
Genetic variants in genes related to obesity are not likely to strongly influence subsequent risk of developing a second primary breast cancer.
genetic variation; obesity; weight; weight change; contralateral breast cancer
Epidemiological evidence continues to accumulate on the benefits of physical activity in relation to cancer risk, progression and mortality. Recent studies suggest that sedentary behavior may independently affect cancer risk; they also focus on factors that may explain associations with physical activity, including cancer risk factors and whether associations exist for precancerous lesions. Despite enormous efforts to examine associations between physical activity and cancer, the literature is hindered by inconsistent assessment of physical activity across studies, and incomplete consideration of variation of effects across population subgroups (for example, defined by body size, age or sex) or tumors subgroups (organ location, receptor status, or molecular subtype), and whether other factors explain study results. Clearly, public health recommendations for appropriate changes in activity levels are needed; unfortunately, at this time, we have no exact physical activity prescription to give to the public.
Review; Physical activity; Cancer risk; Cancer survival; Recreational activity; Occupational activity; Exercise; Biological mechanisms; Methodology; Sedentary behavior; Sitting time; Breast cancer; Colon cancer
This study aimed to determine the prevalence of sarcopenia and examine whether sarcopenia was associated with overall and breast-cancer-specific mortality in a cohort of women diagnosed with breast cancer (stages I–IIIA).
A total of 471 breast cancer patients from western Washington State and New Mexico who participated in the prospective Health, Eating, Activity, and Lifestyle Study were included in this study. Appendicular lean mass was measured using dual X-ray absorptiometry scans at study inception, on average, 12 months after diagnosis. Sarcopenia was defined as two standard deviations below the young healthy adult female mean of appendicular lean mass divided by height squared (<5.45 kg/m2). Total and breast-cancer-specific mortality data were obtained from Surveillance Epidemiology and End Results registries. Multivariable Cox proportional hazard models assessed the associations between sarcopenia and mortality.
Median follow-up was 9.2 years; 75 women were classified as sarcopenic, and among 92 deaths, 46 were attributed to breast cancer. In multivariable models that included age, race-ethnicity/study site, treatment type, comorbidities, waist circumference, and total body fat percentage, sarcopenia was independently associated with overall mortality (hazard ratio (HR)=2.86; 95 % CI, 1.67– 4.89). Sarcopenic women had increased risk of breast-cancer-specific mortality, although the association was not statistically significant (HR=1.95, 95 % CI, 0.87–4.35).
Sarcopenia is associated with an increased risk of overall mortality in breast cancer survivors and may be associated with breast-cancer-specific mortality. The development of effective interventions to maintain and/or increase skeletal muscle mass to improve prognosis in breast cancer survivors warrants further study.
Implications for Cancer Survivors
Such interventions may help breast cancer patients live longer.
Sarcopenia; Appendicular lean mass; Mortality; Breast cancer survivor
To investigate the association between physical activity, body mass
index (BMI) and mammographic density in an ethnically-diverse
population-based sample of 522 postmenopausal women diagnosed with stage
0–IIIA breast cancer and enrolled in the Health, Eating, Activity,
and Lifestyle Study.
We collected information on BMI and physical activity during a clinic
visit two to three years after diagnosis. Weight and height were measured in
a standard manner. Using an interview-administered questionnaire,
participants recalled the type, duration, and frequency of physical
activities in the past year. We estimated dense area and percent density as
a continuous measure using a computer-assisted software program from
mammograms imaged approximately one to two years after diagnosis. Analysis
of covariance methods were used to obtain mean density across World Health
Organization BMI categories and physical activity tertiles adjusted for
We observed a statistically significant decline in percent density (p
for trend = .0001), and mammographic dense area (p for trend = 0.0052), with
increasing level of BMI adjusted for potential covariates. We observed a
statistically significant decline in mammographic dense area (p for trend =
.036) with increasing level of sports/recreational physical activity in
women with a BMI ≥ 30 kg/m2. Conversely, in women with a
BMI < 25 kg/m2, we observed a nonstatistically significant
increase in mammographic dense area and percent density with increasing
level of sports/recreational physical activity.
Increasing physical activity among obese postmenopausal breast cancer
survivors may be a reasonable intervention approach to reduce mammographic
breast cancer; body fat; exercise; obesity; weight; breast tissue; breast density
There is growing evidence linking genetic variations to non–Hodgkin lymphoma (NHL) etiology. To complement ongoing agnostic approaches for identifying susceptibility genes, we evaluated 488 candidate gene regions and their relation to risk for NHL and NHL subtypes.
We genotyped 6,679 tag single nucleotide polymorphisms (SNPs) in 947 cases and 826 population-based controls from a multicenter U.S. case–control study. Gene-level summary of associations were obtained by computing the minimum P value (“minP test”) on the basis of 10,000 permutations. We used logistic regression to evaluate the association between genotypes and haplotypes with NHL. For NHL subtypes, we conducted polytomous multivariate unconditional logistic regression (adjusted for sex, race, age). We calculated P-trends under the codominant model for each SNP.
Fourteen gene regions were associated with NHL (P < 0.01). The most significant SNP associated with NHL maps to the SYK gene (rs2991216, P-trend = 0.00005). The three most significant gene regions were on chromosome 6p21.3 (RING1/RXRB; AIF1; BAT4). Accordingly, SNPs in RING1/RXRB (rs2855429), AIF1 (rs2857597), and BAT4 (rs3115667) were associated with NHL (P-trends ≤ 0.0002) and both diffuse large B-cell and follicular lymphomas (P-trends < 0.05).
Our results suggest potential importance for SYK on chromosome 9 with NHL etiology. Our results further implicate 6p21.3 gene variants, supporting the need for full characterization of this chromosomal region in relation to lymphomagenesis.
Gene variants on chromosome 9 may represent a new region of interesting for NHL etiology. The independence of the reported variants in 6p21.3 from implicated variants (TNF/HLA) supports the need to confirm causal variants in this region
Alcohol consumption increases breast cancer risk, but its effect may be modified by hormone therapy (HT) use, such that exposure to both may be synergistic. Because many women stopped taking HT after mid-2002, it is important to quantify risks associated with alcohol consumption in the context of HT cessation, as these risks may be more relevant to cancer prevention efforts today.
Among 40,680 eligible postmenopausal California Teachers Study cohort participants, 660 were diagnosed with invasive breast cancer before 2010. Multivariate Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI).
Increased breast cancer risk associated with alcohol consumption was observed among postmenopausal women who were current HT users (RR=1.60, 95% CI: 1.13–2.26 and RR=2.11, 95% CI: 1.41–3.15 for <20 and ≥20 g/d of alcohol), with risks being similar by HT preparation. Alcohol did not increase risk among women who had stopped using HT within 3 years or 3–4 years before completing the follow-up questionnaire or in the more distant past. Results were similar for ER+ and ER+PR+ tumors; while power was limited, no increase in risk was observed for ER- tumors.
Following the cessation of HT use, alcohol consumption is not significantly associated with breast cancer risk, although a non-significant increased risk was observed among women who never used HT.
Our findings confirm that concurrent exposure to HT and alcohol has a substantial adverse impact on breast cancer risk. However, after HT cessation, this risk is reduced.
breast cancer; alcohol; hormone therapy; cessation; epidemiology
Brief, valid measures of fatigue, a prevalent and distressing cancer symptom, are needed for use in research. This study’s primary aim was to create a shortened version of the revised Piper Fatigue Scale (PFS-R) based on data from a diverse cohort of breast cancer survivors. A secondary aim was to determine whether the PFS captured multiple distinct aspects of fatigue (a multidimensional model) or a single overall fatigue factor (a unidimensional model).
Breast cancer survivors (n=799; stages in situ through IIIa; ages 29–86 yrs) were recruited through 3 SEER registries (New Mexico, Western Washington, and Los Angeles, CA) as part of the Health, Eating, Activity, and Lifestyle (HEAL) study. Fatigue was measured approximately 3 years post-diagnosis using the 22-item PFS-R that has 4 subscales (Behavior, Affect, Sensory, and Cognition). Confirmatory factor analysis was used to compare unidimensional and multidimensional models. Six criteria were used to make item selections to shorten the PFS-R: scale’s content validity, items’ relationship with fatigue, content redundancy, differential item functioning by race and/or education, scale reliability, and literacy demand.
Factor analyses supported the original 4-factor structure. There was also evidence from the bi-factor model for a dominant underlying fatigue factor. Six items tested positive for differential item functioning between African-American and Caucasian survivors. Four additional items either showed poor association, local dependence, or content validity concerns. After removing these 10 items, the reliability of the PFS-12 subscales ranged from 0.87–0.89, compared to 0.90–0.94 prior to item removal.
The newly developed PFS-12 can be used to assess fatigue in African-American and Caucasian breast cancer survivors and reduces response burden without compromising reliability or validity. This is the first study to determine PFS literacy demand and to compare PFS-R responses in African-Americans and Caucasian breast cancer survivors. Further testing in diverse populations is warranted.
fatigue; breast cancer survivors; patient-reported outcomes; Piper Fatigue Scale; psychometrics
Testicular germ cell tumor (TGCT) incidence increased steadily in recent decades, but causes remain elusive. Germ cell function may be influenced by cannabinoids, and two prior epidemiologic studies report that use of marijuana may be associated with non-seminomatous TGCT. Here we evaluate the relationship between TGCTs and exposure to marijuana and other recreational drugs using a population-based case-control study.
163 TGCT cases diagnosed in Los Angeles County from December 1986 to April 1991 were enrolled with 292 controls matched on age, race/ethnicity and neighborhood. Participants were asked about drug use by structured in-person interview. Odds ratios and 95% confidence intervals were estimated using conditional logistic regression, adjusted for history of cryptorchidism; education; religiosity; and reported use of marijuana, cocaine and amyl nitrite.
Compared to never use, ever use of marijuana had two-fold increased risk (OR=1.94, 95%CI: 1.02–3.68) while ever use of cocaine was negatively associated with TGCT (OR=0.54, 95%CI: 0.32–0.91). Stratification on tumor histology revealed a specific association of marijuana use with non-seminoma and mixed histology tumors (OR=2.42, 95%CI: 1.08–5.42).
We observed a specific association of marijuana use with risk of non-seminoma and mixed tumors. This is the first report of a negative association between cocaine use and TGCT risk. Results warrant mechanistic studies of marijuana’s effect on the endocannabinoid system and TGCT risk, and caution that recreational and therapeutic cannabinoids by young men may confer malignant potential to testicular germ cells.
Testicular Germ Cell Tumors; Non-Seminoma; Marijuana; Cannabis; Δ9-Tetrahydrocannabinol (THC); cocaine; amyl nitrite; recreational drug use; tobacco; alcohol