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Menopausal hormone therapy (MHT) is effective for menopausal symptoms, however, its use is also associated with risks of serious health conditions including breast, ovarian and endometrial cancer, stroke and venous thromboembolism. MHT-related health risks increase with longer durations of use. In Australia, while overall MHT use fell when risk-related findings were published in 2002, a significant number of women continue using MHT long-term. We aimed to examine socio-demographic, health-related and lifestyle characteristics in relation to post-2002 MHT use, and to compare use for <5 and ≥5 years. Data from 1,561 participants from an Australian, national, cross-sectional survey of women aged 50–69 in 2013 were analysed. Odds ratios (ORs) were calculated using logistic regression for characteristics related to overall MHT use post-2002 and multinomial logistic regression for associations between MHT duration of use [never/<5 years/≥5 years] and personal characteristics, adjusting for sociodemographic, reproductive, health and lifestyle factors. Post-2002 MHT use was associated with increasing age (p-trend<0.001), hysterectomy versus no hysterectomy (OR:2.55, 95%CI = 1.85–3.51), bilateral oophorectomy vs no oophorectomy (OR:1.66, 95%CI = 1.09–2.53), and ever- versus never-use of therapies other than MHT for menopausal symptoms (OR:1.93, 95%CI = 1.48–2.57). Women with prior breast cancer (OR:0.35, 95%CI = 0.17–0.74) and with more children (p-trend = 0.034) were less likely than other women to use MHT. Prior hysterectomy was more strongly associated with MHT use for ≥5 years than for <5 years (p = 0.004). Ever-use of non-MHT menopausal therapies was associated with MHT use for <5 years but not with longer-term use (p = 0.004). This study reinforces the need for MHT users and their clinicians to re-evaluate continued MHT use on an ongoing basis. [ABSTRACT FROM AUTHOR]

Estimates of the future breast cancer burden preventable through modifications to current behaviours are lacking. We assessed the effect of individual and joint behaviour modifications on breast cancer burden for premenopausal and postmenopausal Australian women, and whether effects differed between population subgroups. We linked pooled data from six Australian cohort studies (n = 214,536) to national cancer and death registries, and estimated the strength of the associations between behaviours causally related to cancer incidence and death using adjusted proportional hazards models. We estimated exposure prevalence from representative health surveys. We combined these estimates to calculate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), and compared PAFs for population subgroups. During the first 10 years follow‐up, there were 640 incident breast cancers for premenopausal women, 2,632 for postmenopausal women, and 8,761 deaths from any cause. Of future breast cancers for premenopausal women, any regular alcohol consumption explains 12.6% (CI = 4.3–20.2%), current use of oral contraceptives for ≥5 years 7.1% (CI = 0.3–13.5%), and these factors combined 18.8% (CI = 9.1–27.4%). Of future breast cancers for postmenopausal women, overweight or obesity (BMI ≥25 kg/m2) explains 12.8% (CI = 7.8–17.5%), current use of menopausal hormone therapy (MHT) 6.9% (CI = 4.8–8.9%), any regular alcohol consumption 6.6% (CI = 1.5–11.4%), and these factors combined 24.2% (CI = 17.6–30.3%). The MHT‐related postmenopausal breast cancer burden varied by body fatness, alcohol consumption and socio‐economic status, the body fatness‐related postmenopausal breast cancer burden by alcohol consumption and educational attainment, and the alcohol‐related postmenopausal breast cancer burden by breast feeding history. Our results provide evidence to support targeted and population‐level cancer control activities. What's new? While several potentially‐modifiable behavioural risk factors have been identified for breast cancer, estimates of the preventable future breast cancer burden are still lacking. Based on a large prospective pooled Australian cohort, here the authors reveal that regular alcohol consumption is the leading modifiable cause of breast cancer burden for premenopausal women (12.6%). Using the latest exposure prevalence information, the authors rank body fatness as the leading cause of preventable breast cancer burden for postmenopausal women (12.8%), with regular alcohol consumption also contributing substantially (6.6%). The findings provide evidence to support targeted and population‐level cancer control activities in Australia and beyond. [ABSTRACT FROM AUTHOR]

Background: Several evaluations of the cost-effectiveness (CE) of menopausal hormone therapy (MHT) have been reported. The aim of this study was to systematically and critically review economic evaluations of MHT since 2002, after the Women's Health Initiative (WHI) trial results on MHT were published.Methods: The inclusion criteria for the review were: CE analyses of MHT versus no treatment, published from 2002-2016, in healthy women, which included both symptom relief outcomes and a range of longer term health outcomes (breast cancer, coronary heart disease, stroke, fractures and colorectal cancer). Included economic models had outcomes expressed in cost per quality-adjusted life year or cost per life year saved. MEDLINE, EMBASE, Evidence-Based Medicine Reviews databases and the Cost-Effectiveness Analysis Registry were searched. CE evaluations were assessed in regard to (i) reporting standards using the CHEERS checklist and Drummond checklist; (ii) data sources for the utility of MHT with respect to menopausal symptom relief; (iii) cost derivation; (iv) outcomes considered in the models; and (v) the comprehensiveness of the models with respect to factors related to MHT use that impact long term outcomes, using breast cancer as an example outcome.Results: Five studies satisfying the inclusion criteria were identified which modelled cohorts of women aged 50 and older who used combination or estrogen-only MHT for 5-15 years. For women 50-60 years of age, all evaluations found MHT to be cost-effective and below the willingness-to-pay threshold of the country for which the analysis was conducted. However, 3 analyses based the quality of life (QOL) benefit for symptom relief on one small primary study. Examination of costing methods identified a need for further clarity in the methodology used to aggregate costs from sources. Using breast cancer as an example outcome, risks as measured in the WHI were used in the majority of evaluations. Apart from the type and duration of MHT use, other effect modifiers for breast cancer outcomes (for example body mass index) were not considered.Conclusions: This systematic review identified issues which could impact the outcome of MHT CE analyses and the generalisability of their results. The estimated CE of MHT is driven largely by estimates of QOL improvements associated with symptom relief but data sources on these utility weights are limited. Future analyses should carefully consider data sources and the evidence on the long term risks of MHT use in terms of chronic disease. This review highlights the considerable difficulties in conducting cost-effectiveness analyses in situations where short term benefits of an intervention must be evaluated in the context of long term health outcomes. [ABSTRACT FROM AUTHOR]

Menopausal Hormone Therapy (MHT) use in Australia fell by 55% from 2001 to 2005, following the release of large-scale findings on its risks and benefits. Comprehensive national data, including information on overall prevalence of MHT use as well as information on duration of use in Australia have not been reported since the 2004–5 National Health Survey, when 11% of women aged 45+ years were estimated to be current MHT users. No national data are available on prevalence of use of “bioidentical” hormone therapy (BHT). The objective of this study was to determine recent prevalence of MHT and BHT use. A cross-sectional, national, age-stratified, population survey was conducted in 2013. Eligible women, aged 50–69 years, resident in Australia were randomly sampled in 5-year age groups from the Medicare enrolment database (Australia’s universal health scheme). The response rate was 22% based on return of completed questionnaires, and analyses were restricted to 4,389 women within the specified age range. The estimated population-weighted prevalence of current use of MHT was 13% (95%CI 12–14), which was broadly similar to the previously reported national figures in 2004–5, suggesting that the use of MHT in Australia has largely stabilised over the past decade. A total of 39% and 20% of current-users with an intact uterus reported use of oestrogen-progestagen MHT and oestrogen-only MHT, respectively, whereas 77% of hysterectomised current-users used oestrogen-only MHT. Almost three-quarters of current-users [population-weighted prevalence 9% (95%CI 8–10)] had used MHT for ≥5 years. In regard to BHT, estimated population-weighted prevalence of ever use was 6% (95%CI 6–7) and 2% (95%CI 2–3) for current use. The population-weighted prevalence of MHT and BHT combined, in current users in their fifties and sixties was 15% (95%CI 14–16). These data provide a recent national “snapshot” of Australian women’s use of both conventional MHT and of BHT. [ABSTRACT FROM AUTHOR]

Altered protein glycosylation compared with the disease-free state is a universal feature of cancer cells. It has long been established that distinct glycan structures are associated with specific forms of cancer, but far less is known about the complete array of glycans associated with certain tumors. The cancer glycome has great potential as a source of biomarkers, but progress in this field has been hindered by a lack of available techniques for the elucidation of disease-associated glycosylation. In the present study, lectin microarrays consisting of 45 lectins with different binding preferences covering N- and O-linked glycans were coupled with evanescent-field activated fluorescent detection in the glycomic analysis of primary breast tumors and the serum and urine of patients with metastatic breast cancer. A single 50 µm section of a primary breast tumor or <1 µL of breast cancer patient serum or urine was sufficient to detect glycosylation alterations associated with metastatic breast cancer, as inferred from lectin-binding patterns. The high-throughput, sensitive and relatively simple nature of the simultaneous analysis of N- and O-linked glycosylation following minimal sample preparation and without the need for protein deglycosylation makes the lectin microarray analysis described a valuable tool for discovery phase glycomic profiling. [ABSTRACT FROM AUTHOR]

Abstract: Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival. Isoflavones and lignans are the most common phytoestrogens in the diet. In this article, we present findings from human observational and intervention studies related to both isoflavone and lignan exposure and breast cancer risk and survival. In addition, the clinical implications of these findings are examined in the light of a growing dietary supplement market. An increasing number of breast cancer patients seek to take supplements together with their standard treatment in the hope that these will either prevent recurrence or treat their menopausal symptoms. Observational studies suggest a protective effect of isoflavones on breast cancer risk and the case may be similar for increasing lignan consumption although evidence so far is inconsistent. In contrast, short-term intervention studies suggest a possible stimulatory effect on breast tissue raising concerns of possible adverse effects in breast cancer patients. However, owing to the dearth of human studies investigating effects on breast cancer recurrence and survival the role of phytoestrogens remains unclear. So far, not enough clear evidence exists on which to base guidelines for clinical use, although raising patient awareness of the uncertain effect of phytoestrogens is recommended. [Copyright &y& Elsevier]

Background: There is a growing interest in delivering more personalised, risk-based breast cancer screening protocols. This requires population-level validation of practical models that can stratify women into breast cancer risk groups. Few studies have evaluated the Gail model (NCI Breast Cancer Risk Assessment Tool) in a population screening setting; we validated this tool in a large, screened population.Methods: We used data from 40,158 women aged 50-69 years (via the lifepool cohort) participating in Australia's BreastScreen programme. We investigated the association between Gail scores and future invasive breast cancer, comparing observed and expected outcomes by Gail score ranked groups. We also used machine learning to rank Gail model input variables by importance and then assessed the incremental benefit in risk prediction obtained by adding variables in order of diminishing importance.Results: Over a median of 4.3 years, the Gail model predicted 612 invasive breast cancers compared with 564 observed cancers (expected/observed (E/O) = 1.09, 95% confidence interval (CI) 1.00-1.18). There was good agreement across decile groups of Gail scores (χ2 = 7.1, p = 0.6) although there was some overestimation of cancer risk in the top decile of our study group (E/O = 1.65, 95% CI 1.33-2.07). Women in the highest quintile (Q5) of Gail scores had a 2.28-fold increased risk of breast cancer (95% CI 1.73-3.02, p < 0.0001) compared with the lowest quintile (Q1). Compared with the median quintile, women in Q5 had a 34% increased risk (95% CI 1.06-1.70, p = 0.014) and those in Q1 had a 41% reduced risk (95% CI 0.44-0.79, p < 0.0001). Similar patterns were observed separately for women aged 50-59 and 60-69 years. The model's overall discrimination was modest (area under the curve (AUC) 0.59, 95% CI 0.56-0.61). A reduced Gail model excluding information on ethnicity and hyperplasia was comparable to the full Gail model in terms of correctly stratifying women into risk groups.Conclusions: This study confirms that the Gail model (or a reduced model excluding information on hyperplasia and ethnicity) can effectively stratify a screened population aged 50-69 years according to the risk of future invasive breast cancer. This information has the potential to enable more personalised, risk-based screening strategies that aim to improve the balance of the benefits and harms of screening. [ABSTRACT FROM AUTHOR]

Abstract: DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens – naturally occurring plant compounds with oestrogenic properties – and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I–III breast cancer were recruited 9–15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed. [Copyright &y& Elsevier]