IntroductionAssociations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use.MethodsWithin the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed.ResultsFor risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime.ConclusionsAn elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors.

BackgroundThe association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain.MethodsWithin the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors.ResultsA later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] ptrend < 0.001 for ER+PR+ tumors; ≥35 vs. ≤19 years HR: 0.93 [95% CI 0.53-1.65] ptrend = 0.96 for ER-PR- tumors; P het = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (phet = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk.ConclusionOur study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant.

Associations of breast cancer overall with indicators of exposures during puberty are reasonably well characterized; however, uncertainty remains regarding the associations of height, leg length, sitting height and menarcheal age with hormone receptor‐defined malignancies. Within the European Prospective Investigation into Cancer and Nutrition cohort, Cox proportional hazards models were used to describe the relationships of adult height, leg length and sitting height and age at menarche with risk of estrogen and progesterone receptor negative (ER‐PR‐) (n = 990) and ER+PR+ (n = 3,524) breast tumors. Height as a single risk factor was compared to a model combining leg length and sitting height. The possible interactions of height, leg length and sitting height with menarche were also analyzed. Risk of both ER‐PR‐ and ER+PR+ malignancies was positively associated with standing height, leg length and sitting height and inversely associated with increasing age at menarche. For ER+PR+ disease, sitting height (hazard ratios: 1.14[95% confidence interval: 1.08–1.20]) had a stronger risk association than leg length (1.05[1.00–1.11]). In comparison, for ER‐PR‐ disease, no distinct differences were observed between leg length and sitting height. Women who were tall and had an early menarche (≤13 years) showed an almost twofold increase in risk of ER+PR+ tumors but no such increase in risk was observed for ER‐PR‐ disease. Indicators of exposures during rapid growth periods were associated with risks of both HR‐defined breast cancers. Exposures during childhood promoting faster development may establish risk associations for both HR‐positive and −negative malignancies. The stronger associations of the components of height with ER+PR+ tumors among older women suggest possible hormonal links that could be specific for postmenopausal women.

Physical activity is associated with reduced risks of invasive breast cancer. However, whether this holds true for breast cancer subtypes defined by the estrogen receptor (ER) and the progesterone receptor (PR) status is controversial. The study included 257,805 women from the multinational EPIC-cohort study with detailed information on occupational, recreational and household physical activity and important cofactors assessed at baseline. During 11.6 years of median follow-up, 8,034 incident invasive breast cancer cases were identified. Data on ER, PR and combined ER/PR expression were available for 6,007 (67.6%), 4,814 (54.2%) and 4,798 (53.9%) cases, respectively. Adjusted hazard ratios (HR) were estimated by proportional hazards models. Breast cancer risk was inversely associated with moderate and high levels of total physical activity (HR 5 0.92, 95% confidence interval (CI): 0.86-0.99, HR 5 0.87, 95%-CI: 0.79-0.97, respectively; p-trend 5 0.002), compared to the lowest quartile. Among women diagnosed with breast cancer after age 50, the largest risk reduction was found with highest activity (HR 5 0.86, 95%-CI: 0.77-0.97), whereas for cancers diagnosed before age 50 strongest associations were found for moderate total physical activity (HR 5 0.78, 95%-CI: 0.64-0.94). Analyses by hormone receptor status suggested differential associations for total physical activity (p-heterogeneity 5 0.04), with a somewhat stronger inverse relationship for ER1/PR1 breast tumors, primarily driven by PR1 tumors (p-heterogeneity < 0.01). Household physical activity was inversely associated with ER-/PR-tumors. The results of this largest prospective study on the protective effects of physical activity indicate that moderate and high physical activity are associated with modest decreased breast cancer risk. Heterogeneities by receptor status indicate hormone-related mechanisms.

Background and objectives Indigenous Australians experience a heavy burden of CKD. To address this burden, the eGFR Follow-Up Study recruited and followed an Indigenous Australian cohort from regions of Australia with the greatest ESRD burden. We sought to better understand factors contributing to the progression of kidney disease. Specific objectives were to assess rates of progression of eGFR in Indigenous Australians with and without CKD and identify factors associated with a decline in eGFR.Design, setting, participants, & measurements This observational longitudinal study of Indigenous Australian adults was conducted in .20 sites. The baseline cohort was recruited from community and primary care clinic sites across five strata of health, diabetes status, and kidney function. Participants were then invited to follow up at 2-4 years; if unavailable, vital status, progression to RRT, and serum creatinine were obtained from medical records. Primary outcomes were annual eGFR change and combined renal outcome (first of $30% eGFR decline with follow-up eGFR,60 ml/min per 1.73 m 2 , progression to RRT, or renal death).Results Participants (n=550) were followed for a median of 3.0 years. Baseline and follow-up eGFR (geometric mean [95% confidence interval], 83.9 (80.7 to 87.3) and 70.1 (65.9 to 74.5) ml/min per 1.73 m 2 , respectively. Overall mean annual eGFR change was 23.1 (23.6 to 22.5) ml/min per 1.73 m 2 . Stratified by baseline eGFR ($90, 60-89, ,60 ml/min per 1.73 m 2 ), annual eGFR changes were 23.0 (23.6 to 22.4), 21.9 (23.3 to 20.5), and 25.0 (26.5 to 23.6) ml/min per 1.73 m 2 . Across baseline eGFR categories, annual eGFR decline was greatest among adults with baseline albumin-to-creatinine ratio (ACR) .265 mg/g (30 mg/mmol). Baseline determinants of the combined renal outcome (experienced by 66 participants) were higher urine ACR, diabetes, lower measured GFR, and higher C-reactive protein.Conclusions The observed eGFR decline was three times higher than described in nonindigenous populations. ACR was confirmed as a powerful predictor for eGFR decline across diverse geographic regions.

BackgroundGlobally, trachoma is the leading cause of infectious blindness and Australia is the only developed country with endemic trachoma. It is found in remote Indigenous communities burdened with poverty, overcrowding and poor hygiene. Lack of culturally appropriate health promotion, a small trachoma workforce and lack of awareness and support for trachoma elimination in general, were early barriers.MethodsA cross-sectional pre-post study using a convenience sample, was conducted in clinics, schools and community work-settings from 63 of the 82 remote Aboriginal communities identified as being at risk of trachoma in the Northern Territory (NT). The study assessed the effect of a multi-component health promotion strategy aimed at increasing knowledge, attitude and practice amongst health, education and community support settings staff. Data were collected between 2010 and 2012. The health promotion initiatives were introduced in communities in staggered delivery over a one-year period; 272 participants were surveyed at baseline and 261 at follow-up.ResultsTrachoma related knowledge, attitudes and practice increased across all settings and for all primary outcome measures. Across all settings, there was a significant increase in the proportion of participants reporting the most important thing to do if a child has a ‘dirty’ face is to ‘wash it every time its dirty’ (61.6% cf 69.7%; X2p = 0.047), a significant reduction in the proportion of respondents answering ‘no’ to the question “Is it normal for kids to have dirty faces in your community’ (40.5% cf 29.6%; X2p = 0.009) and a significant increase in reported capacity to teach others about trachoma prevention (70.8% cf 83.3%; X2p <0.001).ConclusionHealth promotion was associated with increased trachoma knowledge, attitude and practice amongst health, education and community support staff working with children and in remote NT communities. In the early stages of the trachoma health promotion program, this increased trachoma awareness and improved local workforce capacity and support for trachoma elimination in three health promotion settings in remote communities in the NT.

Objectives: To investigate rates of ‘any’ and ‘predominant’ breastfeeding in hospital among Indigenous and non‐Indigenous women with and without gestational diabetes mellitus (GDM). Methods: A retrospective study of singleton infants born from July 2007 to December 2010 at Cairns Hospital, Australia, following GDM pregnancy, using linked hospital and birth data (n=617 infants), with a subsample of medical record reviews (n=365 infants). Aggregate data were used to compare to breastfeeding rates among infants born following non‐GDM pregnancy (n=7,894 infants). Results: More than 90% of all women reported any breastfeeding before hospital discharge. About 80% of women without GDM reported predominant breastfeeding. Despite significant increases over time (p<0.0001), women with GDM were less likely to predominantly breastfeed (OR 0.32, 95%CI 0.27–0.38, p<0.0001); with lower rates among Indigenous women (53%) compared with non‐Indigenous (60%) women (OR 0.78, 0.70–0.88, p<0.0001); and women having a caesarean birth or pre‐term infant. Conclusions: Rates of predominant in‐hospital breastfeeding were lower among women with GDM, particularly among Indigenous women and women having a caesarean or pre‐term birth. Implications: Strategies are needed to support predominant in‐hospital breastfeeding among women with GDM.

Background: Physical activity has been identified as protective factor for invasive breast cancer risk, whereas comparable studies on in situ carcinoma are rare.Methods: The study included data from 283,827 women of the multinational European Prospective Investigation into C7ancer and Nutrition (EPIC)-cohort study. Detailed information on different types of physical activity conducted during the prior year, such as occupational, recreational, and household activity, as well as on important cofactors, was assessed at baseline. Adjusted HRs for in situ breast cancer were estimated by Cox proportional hazards models.Results: During a median follow-up period of 11.7 years, 1,059 incidents of breast carcinoma in situ were identified. In crude and adjusted multivariable models, no associations were found for occupational, household, and recreational physical activity. Furthermore, total physical activity was not associated with risk of in situ breast cancer. Comparing moderately inactive, moderately active, and active participants with inactive study participants resulted in adjusted HRs of 0.99 [95% confidence interval (CI), 0.83-1.19], 0.99 (95% CI, 0.82-1.20), and 1.07 (95% CI, 0.81-1.40), respectively (P value of trend test: 0.788). No inverse associations were found in any substrata defined by age at diagnosis or body mass index (BMI) status.Conclusions: In this large prospective study, we did not find any evidence of an association between physical activity and in situ breast cancer risk. If not by chance, the contrast between our results for carcinoma in situ and the recognized inverse association for invasive breast cancer suggests that physical activity may have stronger effects on proliferation and late stage carcinogenesis.