Association between antihypertensive medicine use and risk of ovarian cancer in women aged 50 years and older.

BACKGROUND: Epithelial ovarian cancer (EOC) has few modifiable risk factors. There is evidence that some antihypertensive medicines may have cancer preventive and/or therapeutic actions; therefore, we assessed the associations between use of different antihypertensive medicines and risk of specific EOC histotypes. METHODS: Our nested case-control study of linked administrative health data included 6070 Australian women aged over 50 years diagnosed with EOC from 2004 to 2013, and 30,337 matched controls. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between ever use of each antihypertensive medicine group, including beta-adrenergic blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, and alpha blockers, and the risk of EOC overall and separately for the serous, endometrioid, mucinous, clear cell and other histotypes. RESULTS: We found that most antihypertensive medicines were not associated with risk of EOC. However, women who used calcium channel blockers had a reduced risk of serous EOC (OR= 0.89, 95 % CI:0.81,0.98) and use of combination thiazide and potassium-sparing diuretics was associated with an increased risk of endometroid EOC (OR= 2.09, 95 % CI:1.15,3.82). CONCLUSION: Our results provide little support for a chemo-preventive role for most antihypertensives, however, the histotype-specific associations we found warrant further investigation.

Breast cancer treatment disparities in patients with severe mental illness: A systematic review and meta-analysis.

OBJECTIVE: The incidence and mortality rates of breast cancer in individuals with pre-existing severe mental illness (SMI), such as schizophrenia, bipolar disorder, and major depression, are higher than in the general population. Reduced screening is one factor but there is less information on possible barriers to subsequent treatment following diagnosis. METHODS: We undertook a systematic review and meta-analysis on access to guideline-appropriate care following a diagnosis of breast cancer in people with SMI including the receipt of surgery, endocrine, chemo- or radiotherapy. We searched for full-text articles indexed by PubMed, EMBASE, PsycInfo and CINAHL that compared breast cancer treatment in those with and without pre-existing SMI. Study designs included population-based cohort or case-control studies. RESULTS: There were 13 studies included in the review, of which 4 contributed adjusted outcomes to the meta-analyses. People with SMI had a reduced likelihood of guideline-appropriate care (RR = 0.83, 95% CI = 0.77-0.90). Meta-analyses were not possible for the other outcomes but in adjusted results from a single study, people with SMI had longer wait-times to receiving guideline-appropriate care. The results for specific outcomes such as surgery, hormone, radio- or chemotherapy were mixed, possibly because results were largely unadjusted for age, comorbidities, or cancer stage. CONCLUSIONS: People with SMI receive less and/or delayed guideline-appropriate care for breast cancer than the general population. The reasons for this disparity warrant further investigation, as does the extent to which differences in treatment access or quality contribute to excess breast cancer mortality in people with SMI.

Circadian rhythm disrupting behaviours and cancer outcomes in breast cancer survivors: a systematic review.

PURPOSE: Circadian rhythm disruptors (e.g., night-shift work) are risk factors for breast cancer, however studies on their association with prognosis is limited. A small but growing body of research suggests that altered sleep patterns and eating behaviours are potential mechanistic links between circadian rhythm disruptors and breast cancer. We therefore systematically summarised literature examining the influence of circadian rhythm disrupting behaviours on cancer outcomes in women with breast cancer. METHODS: A systematic search of five databases from inception to January 2021 was conducted. Original research published in English, assessing the relationship between post-diagnosis sleep patters and eating behaviours, and breast cancer outcomes were considered. Risk of bias was assessed using the Newcastle-Ottawa Assessment Scale for Cohort Studies. RESULTS: Eight studies published original evidence addressing sleep duration and/or quality (k = 7) and, eating time and frequency (k = 1). Longer sleep duration (≥ 9 h versus [referent range] 6-8 h) was consistently associated with increased risk of all outcomes of interest (HR range: 1.37-2.33). There was limited evidence to suggest that measures of better sleep quality are associated with lower risk of all-cause mortality (HR range: 0.29-0.97). Shorter nightly fasting duration (< 13 h versus ≥ 13 h) was associated with higher risk of all breast cancer outcomes (HR range: 1.21-1.36). CONCLUSION: Our review suggests that circadian rhythm disrupting behaviours may influence cancer outcomes in women with breast cancer. While causality remains unclear, to further understand these associations future research directions have been identified. Additional well-designed studies, examining other exposures (e.g., light exposure, temporal eating patterns), biomarkers, and patient-reported outcomes, in diverse populations (e.g., breast cancer subtype-specific, socio-demographic diversity) are warranted.

Colorectal cancer treatment in people with severe mental illness: a systematic review and meta-analysis.

AIMS: People with severe mental illness (SMI) have a greater risk of dying from colorectal cancer (CRC), even though the incidence is lower or similar to that of the general population This pattern is unlikely to be solely explained by lifestyle factors, while the role of differences in cancer healthcare access or treatment is uncertain. METHODS: We undertook a systematic review and meta-analysis on access to guideline-appropriate care following CRC diagnosis in people with SMI including the receipt of surgery, chemo- or radiotherapy. We searched for full-text articles indexed by PubMed, EMBASE, PsychInfo and CINAHL that compared CRC treatment in those with and without pre-existing SMI (schizophrenia, schizoaffective, bipolar and major affective disorders). Designs included cohort or population-based case-control designs. RESULTS: There were ten studies (sample size = 3501-591 561). People with SMI had a reduced likelihood of surgery (RR = 0.90, 95% CI 0.92-0.97; p = 0.005; k = 4). Meta-analyses were not possible for the other outcomes but in results from individual studies, people with SMI were less likely to receive radiotherapy, chemotherapy or sphincter-sparing procedures. The disparity in care was greatest for those who had been psychiatric inpatients. CONCLUSIONS: People with SMI, including both psychotic and affective disorders, receive less CRC care than the general population. This might contribute to higher case-fatality rates for an illness where the incidence is no higher than that of the general population. The reasons for this require further investigation, as does the extent to which differences in treatment access or quality contribute to excess CRC mortality in people with SMI.

Nitrogen-based Bisphosphonate Use and Ovarian Cancer Risk in Women Aged 50 Years and Older.

BACKGROUND: There are few readily modifiable risk factors for epithelial ovarian cancer; preclinical studies suggest bisphosphonates could have chemopreventive actions. Our study aimed to assess the association between use of nitrogen-based bisphosphonate medicine and risk of epithelial ovarian cancer, overall and by histotype. METHODS: We conducted a case-control study nested within a large, linked administrative dataset including all Australian women enrolled for Medicare, Australia's universal health insurance scheme, between July 2002 and December 2013. We included all women with epithelial ovarian cancer diagnosed at age 50 years and older between July 1, 2004, and December 31, 2013 (n = 9367) and randomly selected up to 5 controls per case, individually matched to cases by age, state of residence, area-level socioeconomic status, and remoteness of residence category (n = 46 830). We used prescription records to ascertain use of nitrogen-based bisphosphonates (ever use and duration of use), raloxifene, and other osteoporosis medicines (no nitrogen-based bisphosphonates, strontium and denosumab). We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression. RESULTS: Ever use of nitrogen-based bisphosphonates was associated with a reduced risk of epithelial ovarian cancer compared with no use (OR = 0.81, 95% CI = 0.75 to 0.88). There was a reduced risk of endometrioid (OR = 0.51, 95% CI = 0.33 to 0.79) and serous histotypes (OR = 0.84, 95% CI = 0.75 to 0.93) but no association with the mucinous or clear cell histotypes. CONCLUSION: Use of nitrogen-based bisphosphonates was associated with a reduced risk of endometrioid and serous ovarian cancer. This suggests the potential for use for prevention, although validation of our findings is required.

Metabolic syndrome and its effect on the outcomes of rheumatoid arthritis in a multi-ethnic cohort in Singapore.

INTRODUCTION: Over-expression of common inflammatory mediators in the metabolic syndrome (MetS) and in rheumatoid arthritis (RA) may lead to mutually adverse outcomes. AIM: We investigate the prevalence of MetS in a multi-ethnic population of RA patients and its effect on clinical and patient-reported outcomes. METHOD: Six hundred sixty RA (561 women) patients from a public-sector specialist clinic in a hospital in Singapore were assessed for MetS according to the 2009 Joint Consensus (JC) and the 2004 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definitions. Univariable and multivariable regression modelling were used to investigate the associations between patients' demographics with MetS and MetS with RA outcomes. RESULTS: The prevalence of MetS in our RA cohort was 49.4% and 44.9% according to the JC and NCEP ATP III definitions, respectively. The diagnosis of MetS was largely due to hypertriglyceridemia, hypertension, and obesity. MetS was associated with older age (OR 1.06 [95% CI 1.04-1.08]), Malay ethnicity (OR 1.78 [95% CI 1.02-3.09]), or Indian ethnicity (OR 3.07 [95% CI 1.68-5.59]). No significant associations between MetS and RA outcomes were observed. RA patients with MetS are more likely to suffer from stroke and ischemic heart disease. CONCLUSION: The prevalence of MetS in RA patients in Singapore was almost double that in the general population. MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease. RA patients, especially those older and of Indian and Malay ethnicities, should be routinely screened for MetS. Any MetS-defining condition should be actively controlled. Key Points • Approximately half of the RA sample from the Singapore RA population can be diagnosed with MetS. • Older patients, and patients of Malay and Indian ethnicities have higher odds of MetS. • MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease.

Intersectional (in) equities in contact coverage of maternal and newborn health services in Nepal: insights from a nationwide cross-sectional household survey.

BACKGROUND: Persistent inequities in coverage of maternal and newborn health (MNH) services continue to pose a major challenge to the health-care system in Nepal. This paper uses a novel composite indicator of intersectional (dis) advantages to examine how different (in) equity markers intersect to create (in) equities in contact coverage of MNH services across the continuum of care (CoC) in Nepal. METHODS: A secondary analysis was conducted among 1978 women aged 15-49 years who had a live birth in the two years preceding the survey. Data were derived from the Nepal Demographic and Health Survey (NDHS) 2016. The three outcome variables included were 1) at least four antenatal care (4ANC) visits, 2) institutional delivery, and 3) postnatal care (PNC) consult for newborns and mothers within 48 h of childbirth. Independent variables were wealth status, education, ethnicity, languages, residence, and marginalisation status. Intersectional (dis) advantages were created using three socioeconomic variables (wealth status, level of education and ethnicity of women). Binomial logistic regression analysis was employed to identify the patterns of (in) equities in contact coverage of MNH services across the CoC. RESULTS: The contact coverage of 4ANC visits, institutional delivery, and PNC visit was 72, 64, and 51% respectively. Relative to women with triple disadvantage, the odds of contact coverage of 4ANC visits was more than five-fold higher (Adjusted Odds Ratio (aOR) = 5.51; 95% CI: 2.85, 10.64) among women with triple forms of advantages (literate and advantaged ethnicity and higher wealth status). Women with triple advantages were seven-fold more likely to give birth in a health institution (aOR = 7.32; 95% CI: 3.66, 14.63). They were also four times more likely (aOR = 4.18; 95% CI: 2.40, 7.28) to receive PNC visit compared to their triple disadvantaged counterparts. CONCLUSIONS: The contact coverage of routine MNH visits was low among women with social disadvantages and lowest among women with multiple forms of socioeconomic disadvantages. Tracking health service coverage among women with multiple forms of (dis) advantage can provide crucial information for designing contextual and targeted approaches to actions towards universal coverage of MNH services and improving health equity.

Colorectal cancer Outcomes in people with Severe Mental Illness Cohort (COSMIC): a protocol for an Australian retrospective cohort using linked administrative data.

INTRODUCTION: Colorectal cancer (CRC) mortality is significantly higher in those with severe mental illness (SMI) compared with the general population, despite similar incidence rates, suggesting that barriers to optimal screening and cancer care may contribute to disparities in CRC mortality in those with SMI. This study aims to compare participation in Australia's National Bowel Cancer Screening Programme (NBCSP) in those with SMI and those in the general population. We will also investigate treatment pathways after diagnosis to determine whether treatment variations could explain differences in CRC mortality. METHODS AND ANALYSIS: We will undertake a retrospective cohort study of Australians using linked administrative data to assess differences in screening and cancer care between those with and without SMI, aged 50-74 years on or after 1 January 2006. People with SMI will be defined using antipsychotic medication prescription data. The comparison group will be people enrolled in Medicare (Australia's universal healthcare system) who have not been prescribed antipsychotic medication. Data on outcomes (NBCSP participation, follow-up colonoscopy, CRC incidence and CRC-cause and all-cause mortality) and confounders will be obtained from national-based and state-based administrative health datasets. All people in New South Wales, aged 50-74 with a new diagnosis of CRC on or after 1 January 2006, will be ascertained to examine stage at diagnosis and cancer treatment in those with and without SMI. Poisson regression will be used to calculate incidence rates and rate ratios for each outcome. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the University of Queensland Human Research Ethics Committee, the Australian Institute of Health and Welfare Ethics Committee and data custodians from every Australian State/Territory. Findings will be disseminated via publications in peer-reviewed journals and presented at appropriate conferences. TRIAL REGISTRATION NUMBER: ACTRN12620000781943.

Hysterectomy with and without oophorectomy and all-cause and cause-specific mortality.

BACKGROUND: Hysterectomy is one of the most commonly performed gynecologic surgeries, with an estimated 30% of women in Australia undergoing the procedure by age of 70 years. In the United States, about 45% of women undergo hysterectomy in their lifetime. Some studies have suggested that this procedure increases the risk of premature mortality. With many women making the decision to undergo hysterectomy for a benign indication each year, additional research is needed to clarify whether there are long-term health consequences of hysterectomy. OBJECTIVE: This study aimed to examine the association between hysterectomy for benign indications, with or without removal of the ovaries, and cause-specific and all-cause mortality. STUDY DESIGN: Our cohort of 666,588 women comprised the female population of Western Australia with linked hospital and health records from 1970 to 2015. Cox regression models were used to assess the association between hysterectomy and all-cause, cardiovascular disease, cancer, and other mortality by oophorectomy type (categorized as none, unilateral, and bilateral), with no hysterectomy or oophorectomy as the reference group. We repeated these analyses using hysterectomy without oophorectomy as the reference group. We also investigated whether associations varied by age at the time of surgery, although small sample size precluded this analysis in women who underwent hysterectomy with unilateral salpingo-oophorectomy. In our main analysis, women who underwent hysterectomy or oophorectomy as part of cancer treatment were retained in the analysis and considered unexposed to that surgery. For a sensitivity analysis, we censored procedures performed for cancer. RESULTS: Compared with no surgery, hysterectomy without oophorectomy before 35 years was associated with an increase in all-cause mortality (hazard ratio, 1.29; 95% confidence interval, 1.19-1.40); for surgery after 35 years of age, there was an inverse association (35-44 years: hazard ratio, 0.93; 95% confidence interval, 0.89-0.97). Similarly, hysterectomy with bilateral salpingo-oophorectomy before 45 years of age was associated with increased all-cause mortality (35-44 years: hazard ratio, 1.15; 95% confidence interval, 1.04-1.27), but decreased mortality rates after 45 years of age. In our sensitivity analysis, censoring gynecologic surgeries for cancer resulted in many cancer-related deaths being excluded for women who did not have surgery for benign indications and thus increased the hazard ratios for the associations between both hysterectomy without oophorectomy and hysterectomy with bilateral salpingo-oophorectomy and risk of all-cause and cancer-specific mortality. The sensitivity analysis therefore potentially biased the results in favor of no surgery. CONCLUSION: Among women having surgery for benign indications, hysterectomy without oophorectomy performed before 35 years of age and hysterectomy with bilateral salpingo-oophorectomy performed before 45 years of age were associated with an increase in all-cause mortality. These procedures are not associated with poorer long-term survival when performed at older ages.

Vitamin D and the gut microbiome: a systematic review of in vivo studies.

PURPOSE: Variation in the human microbiome has been linked with a variety of physiological functions, including immune regulation and metabolism and biosynthesis of vitamins, hormones, and neurotransmitters. Evidence for extraskeletal effects of vitamin D has been accruing and it has been suggested that the effect of vitamin D on health is partially mediated through the microbiome. We aimed to critically evaluate the evidence linking vitamin D and the gastrointestinal microbiome. METHODS: We systematically searched the Embase, Web of Science, PubMed and CINAHL databases, including peer-reviewed publications that reported an association between a measure of vitamin D and the gastrointestinal microbiome in humans or experimental animals. RESULTS: We included 10 mouse and 14 human studies. Mouse studies compared mice fed diets containing different levels of vitamin D (usually high versus low), or vitamin D receptor knockout or Cyp27B1 knockout with wild-type mice. Five mouse studies reported an increase in Bacteroidetes (or taxa within that phylum) in the low vitamin D diet or gene knockout group. Human studies were predominantly observational; all but two of the included studies found some association between vitamin D and the gut microbiome, but the nature of differences observed varied across studies. CONCLUSIONS: Despite substantial heterogeneity, we found evidence to support the hypothesis that vitamin D influences the composition of the gastrointestinal microbiome. However, the research is limited, having been conducted either in mice or in mostly small, selected human populations. Future research in larger population-based studies is needed to fully understand the extent to which vitamin D modulates the microbiome.

Overall Dietary Intake and Prognosis after Breast Cancer: A Systematic Review.

Breast cancer survivors often seek information about how lifestyle factors, such as diet, may influence their prognosis. Previous studies have reviewed evidence around single nutrients, individual foods or food groups. We reviewed studies examining relationships between overall dietary intake and prognosis in breast cancer survivors. A systematic search was conducted to identify studies, published until June 2016, which assessed associations between overall dietary intake (i.e., quality; score; pattern) and mortality and/or recurrence in breast cancer survivors. We identified seven eligible studies. Studies were heterogeneous regarding diet assessment timing (before/after diagnosis); mean age and menopausal status; and dietary intake measure (statistically derived/a priori defined indices). Better overall dietary intake (i.e., better quality; healthy/prudent pattern; less inflammatory diet) was associated with decreased risk of overall and non-breast cancer mortality, in most studies. Insufficient evidence is available to draw conclusions regarding breast cancer-specific survival and disease recurrence. Following breast cancer diagnosis, better overall dietary intake may independently improve overall and non-breast cancer survival. Survivors may improve prognosis by adopting more healthful dietary patterns consistent with dietary guidelines and/or prudent diet. Future adequately powered studies should consider measuring dietary intake consistently to better understand the role of diet in disease-specific outcomes.

Pre-diagnosis diet and survival after a diagnosis of ovarian cancer.

BACKGROUND: The relationship between diet and survival after ovarian cancer diagnosis is unclear as a result of a limited number of studies and inconsistent findings. METHODS: We examined the association between pre-diagnostic diet and overall survival in a population-based cohort (n=811) of Australian women diagnosed with invasive epithelial ovarian cancer between 2002 and 2005. Diet was measured by validated food frequency questionnaire. Deaths were ascertained up to 31 August 2014 via medical record review and Australian National Death Index linkage. We conducted Cox proportional hazards regression analysis, controlling for diagnosis age, tumour stage, grade and subtype, residual disease, smoking status, body mass index, physical activity, marital status, and energy intake. RESULTS: We observed improved survival with highest compared with lowest quartile of fibre intake (hazard ratio (HR)=0.69, 95% CI: 0.53-0.90, P-trend=0.002). There was a suggestion of better survival for women with highest compared with lowest intake category of green leafy vegetables (HR=0.79, 95% CI: 0.62-0.99), fish (HR=0.74, 95% CI: 0.57-0.95), poly- to mono-unsaturated fat ratio (HR=0.76, 95% CI: 0.59-0.98), and worse survival with higher glycaemic index (HR=1.28, 95% CI: 1.01-1.65, P-trend=0.03). CONCLUSIONS: The associations we observed between healthy components of diet pre-diagnosis and ovarian cancer survival raise the possibility that dietary choices after diagnosis may improve survival.

Helplessness/hopelessness, minimization and optimism predict survival in women with invasive ovarian cancer: a role for targeted support during initial treatment decision-making?

PURPOSE: Women with advanced ovarian cancer generally have a poor prognosis but there is significant variability in survival despite similar disease characteristics and treatment regimens. The aim of this study was to determine whether psychosocial factors predict survival in women with ovarian cancer, controlling for potential confounders. METHODS: The sample comprised 798 women with invasive ovarian cancer recruited into the Australian Ovarian Cancer Study and a subsequent quality of life study. Validated measures of depression, optimism, minimization, helplessness/hopelessness, and social support were completed 3-6 monthly for up to 2 years. Four hundred nineteen women (52.5 %) died over the follow-up period. Associations between time-varying psychosocial variables and survival were tested using adjusted Cox proportional hazard models. RESULTS: There was a significant interaction of psychosocial variables measured prior to first progression and overall survival, with higher optimism (adjusted hazard ratio per 1 standard deviation (HR) = 0.80, 95 % confidence interval (CI) 0.65-0.97), higher minimization (HR = 0.79, CI 0.66-0.94), and lower helplessness/hopelessness (HR = 1.40, CI 1.15-1.71) associated with longer survival. After disease progression, these variables were not associated with survival (optimism HR = 1.10, CI 0.95-1.27; minimization HR = 1.12, CI 0.95-1.31; and helplessness/hopelessness HR = 0.86, CI 0.74-1.00). Depression and social support were not associated with survival. CONCLUSIONS: In women with invasive ovarian cancer, psychosocial variables prior to disease progression appear to impact on overall survival, suggesting a preventive rather than modifying role. Addressing psychosocial responses to cancer and their potential impact on treatment decision-making early in the disease trajectory may benefit survival and quality of life.

Circulating 25-hydroxyvitamin D and survival in women with ovarian cancer.

BACKGROUND: Vitamin D status might be associated with cancer survival. Survival after ovarian cancer is poor, but the association with vitamin D has rarely been examined. OBJECTIVE: We evaluated the association between serum 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and ovarian cancer survival. DESIGN: Participants were women with invasive ovarian cancer diagnosed between 2002 and 2005 who participated in the Australian Ovarian Cancer Study. Serum samples, collected at diagnosis (n = 670) or after completion of primary treatment and before recurrence (n = 336), were assayed for 25(OH)D. Sociodemographic, dietary, and lifestyle data came from questionnaires self-completed at recruitment, and clinical and survival data were from medical records, supplemented by linkage to the Australian National Death Index (October 2011). Cox proportional hazards regression was used to estimate HRs and 95% CIs for the association between circulating 25(OH)D and survival. RESULTS: Overall, 59% of the women died during follow-up, with 95% of deaths resulting from ovarian cancer. Circulating 25(OH)D concentrations (mean: 44 nmol/L) were significantly associated with age, state of residence, season of blood collection, and body mass index but not with tumor histology, stage or grade, or comorbidities. Higher 25(OH)D concentrations at diagnosis were significantly associated with longer survival (adjusted HR: 0.93; 95% CI: 0.88, 0.99 per 10 nmol/L), but there was no significant association with progression-free survival or for 25(OH)D measured after primary treatment. CONCLUSIONS: In our cohort, higher serum 25(OH)D concentrations at diagnosis were associated with longer survival among women with ovarian cancer. If confirmed in other studies, this suggests that vitamin D status at diagnosis may be an independent predictor of prognosis. Furthermore, if the association is found to be causal, improving vitamin D status may improve ovarian cancer survival rates.

Aspirin, nonaspirin nonsteroidal anti-inflammatory drugs, acetaminophen and ovarian cancer survival.

Aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to decrease tumor progression in pre-clinical models of ovarian cancer, however the influence of these drugs on survival in women following a diagnosis of ovarian cancer is unknown. We included 1305 Australian women diagnosed with incident invasive epithelial ovarian cancer, recruited into a population-based case-control study. Use of aspirin, nonaspirin NSAIDs and acetaminophen in the 5 years preceding ovarian cancer diagnosis was assessed from self-reports. Deaths were ascertained up to October 2011 via linkage with the Australian National Death Index. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CI). During a mean follow-up time of 4.9 years (SD 2.8 years), there were 834 deaths, of which 779 (93% of deaths) were from ovarian cancer. We found uniformly inverse, but non-significant, HRs for ever use in the last five years of aspirin, nonaspirin NSAIDs and acetaminophen compared with no use (adjusted HRs 0.92 [95% CI 0.81-1.06], 0.91 [95% CI 0.80-1.05] and 0.91 [95% CI 0.69-1.20], respectively). There was no evidence of any dose response trends. The results remained unchanged when we limited the outcome to ovarian cancer mortality. Associations did not differ by histologic subtype, age at diagnosis or stage. Given current interest in the role of aspirin and nonaspirin NSAIDs in cancer survival these results are noteworthy given they are the first to investigate these associations in women with ovarian cancer. Our results provide no strong evidence that pre-diagnostic use of aspirin or nonaspirin NSAIDs are associated with improved survival in women with ovarian cancer.

Toxicity and tolerability of adjuvant breast cancer chemotherapy in obese women.

The purpose of this study was to compare toxicity rates and types between obese and non-obese women during adjuvant chemotherapy for breast cancer, adjusting for regimen type and received dose. We conducted a retrospective cohort study of 537 women receiving chemotherapy, initially treated between 2007 and 2010 at two tertiary hospitals in Brisbane, Australia. Demographic, chemotherapy and toxicity data were extracted from patient charts and analyzed using multivariate logistic regression. Three hundred and seventy-four women were eligible for inclusion. Obese women (body mass index (BMI) > 30 kg/m(2); mean age 52.58 ± 9.49) were older than non-obese women (BMI ≤ 29.9 kg/m(2); mean age 50.19 ± 11.15, P = 0.05) and had more comorbidities (P < 0.01). After adjustment for potential confounders, obesity was not statistically related to chemotherapy-related admission risk (OR 1.27; 95 % CI 0.78-2.09) or febrile neutropenia risk (OR 0.56; 95% CI 0.28-1.21). However, obese women received chemotherapy with proportionally lower mean relative dose intensity than non-obese women (94 vs. 97% of reference dose, P = 0.03). Eighteen (15.8%) obese and zero non-obese women (P < 0.01) had their chemotherapy dose capped at an arbitrary body surface area. Compared with non-obese women, obese women receive different chemotherapy regimens and relatively lower chemotherapy doses. There was no significant evidence of increased toxicity among obese women with either full or adjusted chemotherapy doses. Full body surface areas-based dosing appears to be tolerated as well in obese as in lean women.

Population attributable risk of modifiable risk factors associated with invasive breast cancer in women aged 45-69 years in Queensland, Australia.

OBJECTIVES: To quantify the population attributable risk of key modifiable risk factors associated with breast cancer incidence in Queensland, Australia. STUDY DESIGN: Population attributable fractions (PAFs) for high body mass index (BMI), use of hormone replacement therapy (HRT), alcohol consumption and inadequate physical activity were calculated, using prevalence data from a representative survey of women attending mammographic screening at BreastScreen Queensland in 2008 and relative risk estimates sourced from published literature. Attributable cancers were calculated using 'underlying' breast cancer incidence data for 2008 based on Poisson regression models, adjusting for the inflation of incidence due to the effects of mammographic screening. MAIN OUTCOME MEASURES: Attributable burden of breast cancer due to high body mass index (BMI), use of hormone replacement therapy (HRT), alcohol consumption and inadequate physical activity. RESULTS: In Queensland women aged 45-69 years, an estimated 12.1% (95% CI: 11.6-12.5%) of invasive breast cancers were attributable to high BMI in post-menopausal women who have never used HRT; 2.8% (95% CI: 2.7-2.9%) to alcohol consumption; 7.6% (95% CI: 7.4-7.9%) to inadequate physical activity in post-menopausal women and 6.2% (95% CI: 5.5-7.0%) to current use of HRT after stratification by BMI and type of HRT used. Combined, just over one quarter (26.0%; 95% CI: 25.4-26.6%) of all invasive breast cancers in Queensland women aged 45-69 years in 2008 were attributable to these modifiable risk factors. CONCLUSIONS: There is benefit in targeting prevention strategies to modify lifestyle behaviours around BMI, physical activity, HRT use and alcohol consumption, as a reduction in these risk factors could decrease invasive breast cancer incidence in the Queensland population.

Has the association between hysterectomy and ovarian cancer changed over time? A systematic review and meta-analysis.

Until recently most studies suggested that hysterectomy with ovarian conservation was associated with a decreased risk of ovarian cancer. However, several recent studies have reported modestly increased risks of ovarian cancer following hysterectomy. Given that as many as 35% of women will have a hysterectomy, the nature of the association requires clarification. We conducted a systematic review and meta-analysis of the published literature on the relationship between hysterectomy and ovarian cancer to investigate whether there has been a temporal change in the association. Twenty observational studies that have reported a quantitative assessment of the association between hysterectomy and risk of histologically-confirmed ovarian cancer were included in the meta-analysis. The overall relative risk (RR) estimate was 0.81 (95% confidence interval (CI) 0.72-0.92) suggesting hysterectomy decreases the risk of ovarian cancer. However, there was significant heterogeneity in the results (I(2) = 74%). Our exploration of sources of heterogeneity and metaregression showed that median year of cancer diagnosis of included cases explained most of the heterogeneity relative risk (RR = 0.70 (95% CI 0.65-0.76) for median year diagnosis pre 2000; RR = 1.18 (95% CI 1.06-1.31) for post 2000). This study shows that there has been a temporal shift in the association between hysterectomy and risk of ovarian cancer. One explanation may be the trend away from hysterectomy in younger women. Other speculative possibilities include the decline in oophorectomy rates and the use of oestrogen-only hormone replacement therapy in hysterectomised women. Until further evidence becomes available, clinicians should not advise women that a hysterectomy without salpingo-oophorectomy will favourably influence their future risk of ovarian cancer.

Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: a case-control study, systematic review and meta-analysis.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk of a number of cancer types, however, previous studies of endometrial cancer have yielded inconclusive results. We analyzed data from the Australian National Endometrial Cancer Study (ANECS), a population-based case-control study (1,398 cases, 740 controls). We systematically reviewed all the evidence linking aspirin/NSAIDs use with endometrial cancer and conducted a meta-analysis. For ANECS, unconditional logistic regression was used to estimate odds ratios (OR) adjusting for potential confounders. For the systematic review, we searched Pubmed, Embase, Web of Science and conducted a review of citations from retrieved articles. The meta-analysis risk estimates were pooled using a random-effects model. In our case-control study, women who had ever used aspirin in the last 5 years had a significantly lower risk of endometrial cancer OR = 0.78 [95% confidence interval (CI): 0.63-0.97]. There was a significant inverse dose-response (p-trend <0.001) such that women who reported using ≥2 aspirin/week had almost half the risk OR = 0.54 (0.38-0.78). No significant associations were observed between use of half-aspirin/day, non-aspirin NSAIDs or paracetamol and endometrial cancer risk. The results were similar when examined by cancer subtype. Nine studies were included in the meta-analysis. The overall pooled risk estimate for any versus no use of aspirin was 0.87 (0.79-0.96) with no evidence of heterogeneity. The pooled risk estimate for obese women (BMI ≥ 30 kg/m(2) ) was 0.72 (0.58-0.90) but there was no association for non-obese women. Overall these results suggest that aspirin may reduce the risk of endometrial cancer, particularly among obese women.