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Background Women treated for breast cancer (BC) often suffer genitourinary syndrome of menopause. These symptoms may be alleviated by vaginal estrogen therapy (VET) or menopausal hormone therapy (MHT). However, there are concerns of risks of recurrence of BC and death following treatment. Methods Our study included longitudinal data from a national cohort of postmenopausal women, diagnosed 1997-2004 with early-stage invasive estrogen receptor–positive nonmetastatic BC, who received no treatment or 5 years of adjuvant endocrine therapy. We ascertained prescription data on hormone therapy, VET or MHT, from a national prescription registry. We evaluated mortality and risk of recurrence associated with use of VET and MHT vs non-use using multivariable models adjusted for potential confounders. Results Among 8461 women who had not received VET or MHT before BC diagnosis, 1957 and 133 used VET and MHT, respectively, after diagnosis. Median follow-up was 9.8 years for recurrence and 15.2 years for mortality. The adjusted relative risk of recurrence was 1.08 (95% confidence interval [CI] = 0.89 to 1.32) for VET (1.39 [95% CI = 1.04 to 1.85 in the subgroup receiving adjuvant aromatase inhibitors]) and 1.05 (95% CI = 0.62 to 1.78) for MHT. The adjusted hazard ratios for overall mortality were 0.78 (95% CI = 0.71 to 0.87) and 0.94 (95% CI = 0.70 to 1.26) for VET and MHT, respectively. Conclusions In postmenopausal women treated for early-stage estrogen receptor–positive BC, neither VET nor MHT was associated with increased risk of recurrence or mortality. A subgroup analysis revealed an increased risk of recurrence, but not mortality, in patients receiving VET with adjuvant aromatase inhibitors.

Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values-8 as genome-wide significant, and p-values-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values5. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.

Endometriosis is a hormone-dependent inflammatory disease that is usually characterized by infertility and pain symptoms. This disease mainly occurs during the reproductive years and is rarely diagnosed after menopause. We discuss the physiopathology of this condition after menopause as well as treatment options and the risk of malignant transformation. Occurrence or progression of postmenopausal endometriosis lesions could be related to extra-ovarian production of estrogen by endometriosis lesions and adipose tissue, which becomes the major estrogen-producing tissue after menopause. Postmenopausal women with symptomatic endometriosis should be managed surgically because of the risk of malignancy; medical treatments can be used in cases of pain recurrence after surgery. Aromatase inhibitors act by decreasing extra-ovarian estrogen production and by blocking the feed-forward stimulation loop between inflammation and aromatase within endometriosis lesions. The evidence is currently insufficient to support a conclusion about the optimal hormone replacement therapy for women with endometriosis. The question of malignant transformation of endometriosis in response to hormone replacement therapy in women with a history of endometriosis remains unanswered and needs a long-term follow-up study to evaluate the risk of an adverse outcome. Further studies should be performed to determine the optimal management of menopausal women with endometriosis.

Summary Background High body-mass index (BMI; defined as 25 kg/m 2 or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden of cancer attributable to high BMI in 2012. Methods In this population-based study, we derived population attributable fractions (PAFs) using relative risks and BMI estimates in adults by age, sex, and country. Assuming a 10-year lag-period between high BMI and cancer occurrence, we calculated PAFs using BMI estimates from 2002 and used GLOBOCAN2012 data to estimate numbers of new cancer cases attributable to high BMI. We also calculated the proportion of cancers that were potentially avoidable had populations maintained their mean BMIs recorded in 1982. We did secondary analyses to test the model and to estimate the effects of hormone replacement therapy (HRT) use and smoking. Findings Worldwide, we estimate that 481 000 or 3·6% of all new cancer cases in adults (aged 30 years and older after the 10-year lag period) in 2012 were attributable to high BMI. PAFs were greater in women than in men (5·4% vs 1·9%). The burden of attributable cases was higher in countries with very high and high human development indices (HDIs; PAF 5·3% and 4·8%, respectively) than in those with moderate (1·6%) and low HDIs (1·0%). Corpus uteri, postmenopausal breast, and colon cancers accounted for 63·6% of cancers attributable to high BMI. A quarter (about 118 000) of the cancer cases related to high BMI in 2012 could be attributed to the increase in BMI since 1982. Interpretation These findings emphasise the need for a global effort to abate the increasing numbers of people with high BMI. Assuming that the association between high BMI and cancer is causal, the continuation of current patterns of population weight gain will lead to continuing increases in the future burden of cancer. Funding World Cancer Research Fund International, European Commission (Marie Curie Intra-European Fellowship), Australian National Health and Medical Research Council, and US National Institutes of Health.

Summary Background The risk of venous thrombosis (VT) associated with oral hormone therapy (HT) may differ by type of estrogen compound. Objective To compare the thrombotic profile of women using oral conjugated equine estrogens (CEE) with that of women using oral estradiol (E2). Methods In postmenopausal, female, health maintenance organization (HMO) members with no history of VT, we measured thrombin generation, levels of factor VII activity, antithrombin activity and total protein S antigen. Mean levels of hemostasis biomarkers were cross-sectionally compared by use and type of estrogen using multiple linear regressions. The type of estrogen used was determined primarily by the HMO formulary, which changed its preferred estrogen from CEE to E2 during the study period. Results The sample included 92 E2 users and 48 CEE users, with a mean age of 64.1 years and mean BMI of 29.1 kg m−2. Twenty-seven per cent of HT contained medroxyprogesterone acetate. Compared with E2 users, CEE users had greater thrombin generation peak values and endogenous thrombin potential, and lower total protein S (multivariate adjusted differences of 49.8 nm (95% CI, 21.0, 78.6), 175.0 nm × Min (95% CI, 54.4, 295.7) and −13.4% (95% CI, −19.8, −6.9), respectively). Factor VII and antithrombin levels were not different between E2 and CEE users. Results were similar in subgroups of users of unopposed HT, opposed HT, low-dose estrogen and standard dose estrogen. Conclusion The hemostatic profile of women using CEE is more prothrombotic than that of women using E2. These findings provide further evidence for a different thrombotic risk for oral CEE and oral E2.