Hormone Therapy Users Research Articles

Coronary heart disease mortality and hormone therapy before and after the Women's Health Initiative.

To assess whether coronary heart disease mortality in Finnish hormone therapy (HT) users differed before and after 2002 when the Women's Health Initiative study was published. The risks of coronary heart disease death in HT users in relation to the age-matched background population were compared between the pre- (1995-2001) and post- (2002-2009) Women's Health Initiative eras. We used a nationwide register on HT (ie, estradiol with or without progestin) reimbursement and linked them to causes of death in 290,272 women aged 40 years or older. Exposure to HT for 1 year or less was accompanied by a 29% reduction (0.71; 0.63-0.80; three per 10,000 fewer deaths) and an exposure of 1-8 years with a 43% reduction (0.57; 0.48-0.66; three per 10,000 fewer deaths) in the risk of coronary heart disease death in the pre-Women's Health Initiative era. In the post-Women's Health Initiative era, HT use of 1 year or less was associated with an 18% reduction (0.82; 0.76-1.00; one per 10,000 fewer deaths) and an exposure of 1-8 years with a 54% reduction (0.46; 0.32-0.64; two per 10,000 fewer deaths) in coronary heart disease mortality. Discontinuation of HT was associated with an increased risk of cardiac death of 42% (1.42; 1.17-1.71; seven per 10,000 extra deaths) in the pre-Women's Health Initiative era and 31% (1.31; 0.92-1.82; two per 10,000 extra deaths) in the post-Women's Health Initiative era during the first posttreatment year. This risk increase vanished in further follow-up during both eras. Changes in HT use after the Women's Health Initiative failed to affect coronary heart disease mortality of HT users in this nationwide study.

Prolactin determinants in healthy women: A large cross-sectional study within the EPIC cohort.

Experimental and epidemiologic data suggest that higher circulating prolactin is associated with breast cancer risk; however, how various risk factors for breast cancer influence prolactin levels in healthy women is not clear. We analyzed cross-sectional associations between several suggested reproductive and lifestyle risk factors for breast cancer and circulating prolactin among pre- and postmenopausal women, taking into account the use of current postmenopausal hormone therapy, among 2,560 controls from a breast cancer nested case-control study within the EPIC cohort. Adjusted geometric mean prolactin levels were significantly higher among premenopausal women, and among postmenopausal women using hormone therapy compared with nonusers (8.2, 7.0, and 6.3 ng/mL, respectively; Pcat = <0.0001). Furthermore, prolactin levels were significantly higher among users of combined estrogen-progestin hormone therapy compared with users of estrogen-alone hormone therapy (6.66 vs. 5.90 ng/mL; Pcat = 0.001). Prolactin levels were lower among parous women compared with nulliparous women (8.61 vs. 10.95 ng/mL; Pcat = 0.0002, premenopausal women); the magnitude of this difference depended on the number of full-term pregnancies (22.1% lower, ≥3 vs. 1 pregnancy, Ptrend = 0.01). Results for parity were similar but lower in magnitude among postmenopausal women. Prolactin did not vary by other studied factors, with the exception of lower levels among postmenopausal smokers compared with never smokers. Our study shows that current hormone therapy use, especially the use of combined hormone therapy, is associated with higher circulating prolactin levels in postmenopausal women, and confirms prior findings of lower circulating prolactin in parous women. Our study extends the knowledge linking various breast cancer risk factors with circulating prolactin.

The association of chemotherapy versus hormonal therapy and health outcomes among patients with hormone receptor-positive, HER2−negative metastatic breast cancer: experience from the patient perspective

This study aimed to characterize the impact of metastatic breast cancer (MBC) and cancer treatments on health-related quality of life, treatment satisfaction, and daily productivity from the patient perspective. This was a cross-sectional survey of patients with MBC (USA, n = 200; EU, n = 160). Post-menopausal women aged ≥50 years with hormone receptor positive (HR+), HER2−negative (HER2−) MBC, currently using hormonal therapy (HT) or using chemotherapy (CT) for ≤1 year were recruited. Fifty three percent (n = 191) reported CT and 47% (n = 169) reported HT use. Adjusting for covariates, HT users reported greater health-related quality of life (p < 0.05), greater satisfaction with treatment and better feelings about side-effects (p < 0.001). HT users reported less bother with treatment side-effects (0–5 scale, p < 0.001) and less activity impairment than CT users (p < 0.001). HT was associated with better patient-reported outcomes than CT in first-line MBC management. These findings should be taken into consideration while making treatment decisions for HR+/HER2− MBC.

Health characteristics of women beginning postmenopausal hormone therapy

After we demonstrated a substantial drop in postmenopausal hormone therapy (HT) in France after 2002, we sought to compare health characteristics assessed before menopause and reasons for beginning treatment among women who started postmenopausal HT before and after this year. Among participants of the GAZEL (GAZ and ELectricité) cohort of employees of the French national power company, we studied 1,229 women who reached menopause before 2002 and 562 women who reached menopause after 2002. We analyzed HT use among these newly postmenopausal women before and after 2002 and its relations to self-rated health, simple and troublesome hot flushes, and various other symptoms before menopause. After 2002, compared with before 2002, women starting HT were more likely to have reported troublesome hot flushes before menopause (odds ratio, 2.3; 95% CI, 1.0-5.4). The groups of new HT users did not differ significantly except for health characteristics. Significantly higher proportions of women starting HT reported using it for hot flushes (68.1% vs 52.9%, P = 0.02) and sleep disorders (11.1% vs 2.8%, P = 0.001) and a significantly lower proportion of women starting HT reported using it for osteoporosis prevention (12.5% vs 43.9%, P < 0.001) after 2002 than before 2002. After 2002, HT tended to be prescribed for more severe hot flushes, but almost one third of prescriptions were still written for reasons not linked to hot flushes. Doctors seem to be following recommendations to not use HT as a first-line treatment of osteoporosis.

Carotid intima-media thickness and calcification in relation to bone mineral density in postmenopausal women—The OSTPRE-BBA study

ObjectivesAtherosclerosis (AS) and osteoporosis are common diseases in elderly people and may be metabolically related. The aim of this cross-sectional population-based study was to explore the association between common carotid artery intima-media thickness (cIMT), carotid artery calcification (CAC), and BMD in postmenopausal women. In addition, the association of postmenopausal hormone therapy (HT) and selected diseases with cIMT and carotid calcification was studied. Study designThe 290 women (mean age 73.6 years) included in this Bone Brain Atherosclerosis study (OSTPRE-BBA) were randomly selected from the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort, Finland. Main outcome measuresFor this cross-sectional study, cIMT was measured with B-mode ultrasound; femoral neck and total body BMD were measured with dual-energy X-ray absorptiometry. ResultsThere were no statistically significant associations between mean cIMT and femoral neck T-score (p>0.05). However, an increased maximum cIMT was significantly associated with low femoral neck T-score. In the osteoporotic group (T-score <−2.5, n=20), the maximum cIMT was 2.51±0.88mm (mean±SD); in the normal BMD group (T-score >−1, n=122), it was 1.93±0.64mm (p=0.001). The odds of having CAC were approximately four-fold higher in the osteoporotic group compared with the group with a normal femoral neck T-score (odds ratio [OR]=4.2, p=0.038). The maximum cIMT was smaller in HT users (1.98±0.56mm, n=190) than in non-users (2.16±0.74mm, n=156, p=0.036). ConclusionsThe results of our population-based study suggest that BMD is related to AS, at least in carotid arteries. They indirectly support the hypothesis of partially shared pathophysiological mechanisms between these two disorders.

Differential associations of oral estradiol and conjugated equine estrogen with hemostatic biomarkers

The risk of venous thrombosis (VT) associated with oral hormone therapy (HT) may differ by type of estrogen compound. To compare the thrombotic profile of women using oral conjugated equine estrogens (CEE) with that of women using oral estradiol (E2). 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. 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. 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.

Modulation of age- and cancer-associated DNA methylation change in the healthy colon by aspirin and lifestyle.

BackgroundAberrant DNA methylation in gene promoters is associated with aging and cancer, but the circumstances determining methylation change are unknown. We investigated the impact of lifestyle modulators of colorectal cancer (CRC) risk on the stability of gene promoter methylation in the colonic mucosa.MethodsWe measured genome-wide promoter CpG methylation in normal colon biopsies (n = 1092) from a female screening cohort, investigated the interaction of lifestyle factors with age-dependent increase in methylation with log-linear multivariable regression, and related their modifying effect to hypermethylation in CRC. All statistical tests were two-sided.ResultsOf 20025 promoter-associated CpGs analyzed, 1713 showed statistically significant age-dependent methylation gains. Fewer CpGs acquired methylation in users of aspirin (≥2 years) and hormonal replacement therapy (HRT age ≥50 years) compared with nonusers (43 vs 1355; 1 vs1377, respectively), whereas more CpGs were affected in smokers (≥20 years) and individuals with a body mass index (BMI) of 25kg/m2 and greater compared with control groups (180 vs 39; 554 vs 144, respectively). Fifty percent of the CpGs showing age-dependent methylation were found hypermethylated in CRC (odds ratio [OR] = 20; 95% confidence interval [CI] = 18 to 23; P < 2×10–16). These loci gained methylation with a higher median rate compared with age-only methylated sites (P = 2×10–76) and were enriched for polycomb regions (OR = 3.67). Importantly, aspirin (P < .001) and HRT use (P < .001) reduced the methylation rate at these cancer-related genes, whereas smoking (P < .001) and high BMI (P = .004) increased it.ConclusionsLifestyle, including aspirin use, modulates age-associated DNA methylation change in the colonic epithelium and thereby impacts the evolution of cancer methylomes.

PCN159 - The Association of Chemotherapy Versus Hormonal Therapy and Health Outcomes Among Patients with Hormone Receptor-Positive, Her2-Negative Metastatic Breast Cancer: Experience From the Patient Perspective

Health-related quality of life (HRQoL) is essential in treatment decisions for metastatic breast cancer (mBC), therefore, it’s important to understand the impact of treatment on patient-reported outcomes (PRO) in a real-world setting. This study aims to characterize the impact of mBC and cancer treatments on HRQoL, treatment satisfaction and daily productivity from the patient perspective. This is a cross-sectional survey of 360 patients with mBC (US, n=200; EU, n=160). Post-menopausal women aged ≥50 years, with hormone receptor positive (HR+), HER2-negative (HER2-) mBC, currently using hormonal therapy (HT) or using chemotherapy (CT) for ≤1 year were recruited. The Functional Assessment of Cancer Therapy–Breast (FACT-B), Work Productivity and Activity Impairment, Cancer Treatment Satisfaction Questionnaire (CTSQ), patient-centric questions related to mBC, demographics, and adverse events (AEs) were assessed across CT and HT users. Multivariate analyses compared CT vs. HT with adjustments for demographics, comorbidities, and disease/treatment related measures. Among the 360 patients, 53% (n=191) reported CT and 47% (n=169) reported HT use. Patient characteristics were generally similar between treatment cohorts with an average age of 58.3 years (SD=6.3). HT users reported higher FACT-B scores (78.0 vs. 70.1, p<0.001), higher scores on the FACT-B subscales (physical, emotional and functional well-being, and breast cancer, p<0.05 for all), greater satisfaction with treatment (subscale of the CTSQ; 74.1 vs. 67.2, p<0.001), and better feelings about side-effects (subscale of the CTSQ; 48.2 vs. 41.6, p<0.001). HT users reported less bother with treatment AEs (0-5 scale, 1.0 vs. 1.3, p<0.001) and less activity impairment compared with CT (52.6% vs. 60.8%, p<0.001). Findings suggest that HT is associated with better HRQoL, greater treatment satisfaction, less treatment related AEs, and less activity impairment compared with CT in 1st line mBC. These findings should be taken into consideration while making treatment decisions for HR+/HER2- mBC.

Use and discontinued use of menopausal hormone therapy by healthy women in Norway

This work aims to study the use of hormone therapy (HT) in a representative cohort of Norwegian women during the menopausal transition, to identify predictors of HT use, and to describe the reappearance of symptoms in former HT users. In 1997, 2,229 women in Hordaland County, aged 40 to 44 years, were selected randomly from a national health survey and followed up with seven postal questionnaires in 1999-2010. Data from 2,002 women (90%) were eligible for analysis. Summary statistics and multiple logistic regression analysis were used. We studied the reappearance of symptoms after HT discontinuation using a subcohort based on their propensity scores for HT use. The 2-year incidence of new HT users dropped from 8.2% (95% CI, 7.0-9.5) in 2002 to 4.3% (95% CI, 3.4-5.2) in 2004 and remained stable despite an increasing prevalence of symptoms in the cohort. Self-rated health was stable during the period. The mean duration of HT use was 4.5 years (95% CI, 4.0-5.0). The odds of HT use were higher among women with daily hot flushes than among those who never or rarely experienced them (odds ratio, 3.2; 95% CI, 2.3-4.4). After HT cessation, hot flushes returned and corresponded to those in untreated controls. The 2-year incidence of HT users decreased almost 50% after 2002. Increasing symptoms and decreasing incidence of HT use did not influence self-rated health. Hot flushes were the strongest predictor of HT use. Symptoms reappeared in most women after HT cessation.

Abstract P377: Oral Estrogen Hormone Therapy Use after Incident Venous Thrombosis and the Risk of Recurrence

Background: Oral estrogen hormone therapy (HT) is associated with a 2-fold increased risk of incident venous thrombosis (VT). Patterns of HT use following an incident VT and the association between HT use and recurrence are poorly characterized. Objectives: We aimed: (1) to characterize the use of oral estrogen HT in the 5 months following a first VT event; and (2) to evaluate whether the use of HT following an incident VT is associated with VT recurrence. Methods: In Group Health Cooperative (GHC), an integrated health care system, we identified an inception cohort of women aged 40-89 who experienced an incident VT from 2002 to 2010 (n=1,121). Using medical record review, we followed participants for VT recurrence, defined by physician diagnosis &gt;2 weeks after the incident VT with clinical and/or imaging evidence of a new or expanded clot. HT use at 80% compliance was defined using GHC computerized pharmacy data. Characterization of HT use was restricted to women who survived for ≥5 months. Cox proportional hazards models were used to evaluate the association between time-varying current HT use and risk of recurrent VT, adjusting for race, baseline age, BMI, idiopathic incident VT, diabetes status, and the following time-varying covariates: cancer, CVD, and current anticoagulation use. In primary analyses, time was defined as days since incident event and censoring occurred at last follow-up or death. To evaluate the influence of possible HT misclassification soon after the incident event, we conducted 2 sensitivity analyses in which women entered the risk set after 30 and 60 days post-incident VT. Additional secondary Cox analyses were restricted to current HT users at the time of incident VT. Results: Of women who survived ≥5 months post-incident VT (n=993), 12% used oral estrogen HT at time of the incident event (n=123); among these, 90 (73%) discontinued use whereas 33 (27%) continued to fill ≥1 HT prescription within the next 5 months. Compared with users who stopped HT, persistent users were on average older (70 vs. 65 years), had a lower BMI (29 vs. 32 kg/m 2 ), and were less likely to have experienced an incident PE as part of their first VT event (27% vs. 61%). Over an average follow-up of 3.4 years, we identified 164 recurrent VTs among 1,121 women. We found no evidence of an association between HT use after incident VT and VT recurrence risk, adjusted for confounders (HR=0.73; 95% CI: 0.26-1.99; p=0.53); no evidence of an association was found in sensitivity or secondary analyses. Conclusions: In this population of GHC enrollees, over one-quarter of oral estrogen HT users at VT incidence continued use and filled subsequent HT prescriptions in the 5 months following the incident event. We found no evidence of an association between post-event HT use and the risk of VT recurrence, however, the number of HT users in our population was small.

Association of ischemic stroke, hormone therapy, and right to left shunt in postmenopausal women

Postmenopausal hormone therapy (HT) increases the risk of venous thrombosis and ischemic stroke. We postulated that HT might increase the risk of ischemic stroke by promoting venous clots that travel to the brain through a right to left shunt (RLS). A total of 2,389 records were studied. After eliminating the premenopausal patients, and those with TIAs and non-ischemic strokes, the medical records of 1846 postmenopausal women hospitalized at four institutions for ischemic stroke were reviewed to identify those who had undergone an adequate study to assess for RLS. The proportion of women with a shunt in users and non-users of HT was compared in stroke patients and in a reference population consisting of postmenopausal women undergoing elective cardiac catheterization. There were 363 (20%) records that had complete data and were included in the analysis. A shunt was more prevalent in patients with a cryptogenic stroke than in patients with a stroke of known cause (55/88 (63%) vs. 53/275 (19%), P < 0.001). In patients with a stroke of known cause, the frequency of a shunt was similar to that in reference women 31/136 (23%), and the proportion of women with a shunt was similar in non-users and current users of HT (14% vs. 20%, P = 0.40). However, among patients with a cryptogenic stroke, the prevalence of a shunt was 1.5 times higher in current users than non-users of HT (82% vs. 56%, P = 0.04). Approximately 23% of older women have a RLS. HT in these women may increase the risk of ischemic stroke by promoting paradoxical embolism.

Abstract T MP67: Physical Activity Reduces Stroke Risk Among Women in the California Teachers Study Cohort

Background: Major modifiable stroke risk factors are well-established, yet strategies for effective prevention remain challenging. Developing stroke prevention strategies for women is critical due to: (i) the higher fatality and disability rate that women suffer compared to men, (ii) the unique risks to women such as from post-menopausal hormone therapy use, and (iiii) the aging female population. We evaluated three important modifiable stroke risk factors- obesity, hormone therapy, and physical activity, in the California Teachers Study cohort to identify potential stroke prevention strategies. Methods: The California Teachers Study comprises 133,479 women who enrolled in 1995 and have since been continuously followed. Using linked California state hospitalization data from 1996-2010, 3126 stroke events were defined as ischemic (N=2416; ICD-9 433, 434, 436) or hemorrhagic (N=710; ICD-9 430-432, excluding 432.1) and were validated by medical record review. Information about obesity, physical activity, hormone therapy, and medical history was collected at baseline and in follow-up questionnaires. Multivariable-adjusted hazards ratios and 95% confidence intervals were estimated by fitting Cox proportional hazards models with follow-up through 2010. Results: Consistent with previous reports, current post-menopausal hormone therapy use was associated with a 1.3-fold increased risk for stroke (95% CI=1.03-4.85). Moderate to strenuous physical activity in the 3 years before enrollment (but not lifetime activity) decreased stroke risk by 20% (HR=0.79, 95% CI=0.71-0.98). This decreased risk among physically active women was similar among current hormone therapy users, and appears to counteract the increased risk observed with current hormone therapy use. We found no association between obesity and stroke that was independent of diabetes. Conclusions: Recent physical activity reduces stroke risk and appears to counteract the increased risk associated with post-menopausal hormone therapy use.

Hormone therapy and venous thromboembolism among postmenopausal women.

Venous thromboembolism (VTE) is a major harmful effect of hormone therapy (HT) among postmenopausal women. A large variety of HT can be used with significant differences in adverse effects. There is evidence that the VTE risk among HT users depends on the route of estrogen administration. Oral but not transdermal estrogens dose-dependently increase the VTE risk. This difference is supported by biological data. Whereas oral estrogens increase thrombin generation and induce resistance to activated protein C, transdermal estrogens have minimal effect on hemostasis. Past users of oral estrogens have a similar VTE risk to never users. Among users of oral estrogens, the VTE risk is higher within the 1st year of treatment. The combination of oral estrogen use and either obesity or thrombogenic mutations further enhances the VTE risk, whereas transdermal estrogens may not confer additional risk in women at high VTE risk. Significant differences in the VTE risk between HT preparations are also related to the type of concomitant progestogen. The VTE risk is greater in women using medroxyprogesterone acetate than in those receiving other progestins, whereas micronized progesterone appears safe. Based on the current data, transdermal estrogen alone or combined with progesterone could be the safer HT especially in women at high risk for thrombosis.

Lower Risk of Cardiovascular Events in Postmenopausal Women Taking Oral Estradiol Compared With Oral Conjugated Equine Estrogens

Little is known about the comparative cardiovascular safety of oral hormone therapy products, which impedes women from making informed safety decisions about hormone therapy to treat menopausal symptoms. To compare the relative clinical cardiovascular safety of 2 commonly used oral estrogen drugs-conjugated equine estrogens (CEEs) and estradiol. Population-based, case-control study from January 1, 2003, to December 31, 2009, comparing cardiovascular event risk associated with current CEEs and estradiol use in a large health maintenance organization in which the preferred formulary estrogen changed from CEEs to estradiol during the course of data collection. Participants were 384 postmenopausal women aged 30 to 79 years using oral hormone therapy. Incident venous thrombosis was the primary clinical outcome, and incident myocardial infarction and ischemic stroke were secondary outcomes. As validation, an intermediate clotting phenotype, the endogenous thrombin potential-based normalized activated protein C sensitivity ratio, was measured in plasma of controls. We studied 68 venous thrombosis, 67 myocardial infarction, and 48 ischemic stroke cases, with 201 matched controls; all participants were current users of oral CEEs or estradiol. In adjusted analyses, current oral CEEs use compared with current oral estradiol use was associated with an increased venous thrombosis risk (odds ratio, 2.08; 95% CI, 1.02-4.27; P = .045) and an increased myocardial infarction risk that did not reach statistical significance (odds ratio, 1.87; 95% CI, 0.91-3.84; P = .09) and was not associated with ischemic stroke risk (odds ratio, 1.13; 95% CI, 0.55-2.31; P = .74). Among 140 controls, CEEs users compared with estradiol users had higher endogenous thrombin potential-based normalized activated protein C sensitivity ratios (P < .001), indicating a stronger clotting propensity. In an observational study of oral hormone therapy users, CEEs use was associated with a higher risk of incident venous thrombosis and possibly myocardial infarction than estradiol use. This risk differential was supported by biologic data. These findings need replication and suggest that various oral estrogen drugs may be associated with different levels of cardiovascular risk.

Abstract P1-13-01: Risk of recurrence following 5 years of adjuvant hormone therapy for hormone receptor positive early breast cancer.

Abstract Background Introduction The MA.17 study and combined analysis of the ATLAS and aTTom studies provide evidence of DFS and modest OS benefit from 10 years of hormone therapy (HT) for hormone receptor positive early breast cancer. The benefit may be less for women diagnosed today, due to advances in chemotherapy, initial HT, and radiation therapy since the era when these trials were conducted. Side effects accrue to all users of longer HT while benefit is experienced only by those who avoid recurrence, which is related to the baseline prognostic factors such as stage, grade, and disease biology. Methods To enhance informed patient-physician discussions, starting with a cohort of 10815 stage I-III hormone receptor breast cancer diagnoses between 1989 and 2004, we examined event-free survival (EFS) in years 5 to 10 among 1,061 premenopausal (&amp;lt;45 years at diagnosis) and 6,615 menopausal (≥50 years at diagnosis) women without documented relapse, CLBC, or death within the first 5 years. All patients were referred to the BC Cancer Agency (BCCA) with newly diagnosed disease, and all patients had adjuvant HT. EFS was defined as freedom from recurrence, from CLBC, or from breast cancer death without prior documented recurrence. Results Median follow up for the 7676 patients is 11 years. Event rates (including CLBC) in the second 5 years from diagnosis for stage I, II and III cancers were 6%, 12%, 23% for the pre-menopausal cohort, and 5%, 14%, 26% for the post-menopausal cohort. EFS in years 5-10 varied significantly by grade as shown below: EFS years 5-10 after ER+ early Breast CancerStage, gradeAge 45 and younger at diagnosisAge 50 and older at diagnosis NEvents% EFS years 5-10 (95% CI)NEvents% EFS years 5-10 (95% CI)I, grade 1110698.2 (92.9,99.5)10375795.4 (93.7,96.6)I, grade 21741692.1 (86.7,95.3)133811194.6 (93.1,95.7)I, grade 368593.4 (83.2,97.5)3642994.8 (91.8,96.8)II, grade 174889.6 (78.0,95.3)6056193.0 (90.5,94.9)II, grade 22905186.3 (81.6,89.9)177330786.6 (84.8,88.2)II, grade 32103090.4 (85.4,93.8)82318781.9 (78.9,84.5)III, grade 160100531175.6 (59.6,86.0)III, grade 2591574.3 (60.6,84.1)2526774.3 (67.8,79.8)III, grade 3521178.0 (62.1, 87.9)1504072.0 (62.8,79.3)CI, confidence Intervals Recurrences (excluding CLBC) after 10 years was 2% for the 10815 cases (representing 12% of all recurrences). Conclusion These data suggest that pre and postmenopausal women with stage I cancers of any grade, and postmenopausal women with stage II grade 1 cancers who have not experienced a relapse in the first five years can expect a less than 10% risk of recurrence, breast cancer death, or CLBC without further HT over the next 5 years. Prolonged HT in the identified groups may result in higher probability of harm than benefit and may best be avoided, although long term data will be needed to fully inform this risk benefit analysis. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-01.

For Cardiovascular Risk, Not All Oral Menopausal Estrogen Formulations Are Alike

Although many studies have compared cardiovascular risks in menopausal hormone therapy users versus nonusers, few data address the comparative safety

Reduced breast cancer incidence in women treated with subcutaneous testosterone, or testosterone with anastrozole: A prospective, observational study

ObjectivesThere is evidence that androgens are breast protective and that testosterone therapy treats many symptoms of hormone deficiency in both pre and postmenopausal patients. However, unlike estrogen and progestins, there is a paucity of data regarding the incidence of breast cancer in women treated with testosterone therapy. This study was designed to investigate the incidence of breast cancer in women treated with subcutaneous testosterone therapy in the absence of systemic estrogen therapy. Study designThis is a 5-year interim analysis of a 10-year, prospective, observational, IRB approved study investigating the incidence of breast cancer in women presenting with symptoms of hormone deficiency treated with subcutaneous testosterone (T) implants or, T combined with the aromatase inhibitor anastrozole (A), i.e., T+A implants. Breast cancer incidence was compared with that of historical controls reported in the literature, age specific Surveillance Epidemiology and End Results (SEER) incidence rates, and a representative, similar age group of our patients used as a ‘control’ group. The effect of adherence to T therapy was also evaluated. ResultsSince March 2008, 1268 pre and post menopausal women have been enrolled in the study and eligible for analysis. As of March 2013, there have been 8 cases of invasive breast cancer diagnosed in 5642 person-years of follow up for an incidence of 142 cases per 100000 person-years, substantially less than the age-specific SEER incidence rates (293/100000), placebo arm of Women's Health Initiative Study (300/100000), never users of hormone therapy from the Million Women Study (325/100000) and our control group (390/100000). Unlike adherence to estrogen therapy, adherence to T therapy further decreased the incidence of breast cancer (73/100000). ConclusionT and/or T+A, delivered subcutaneously as a pellet implant, reduced the incidence of breast cancer in pre and postmenopausal women. Evidence supports that breast cancer is preventable by maintaining a T to estrogen ratio in favor of T and, in particular, by the use of continuous T or, when indicated, T+A. This hormone therapy should be further investigated for the prevention and treatment of breast cancer.

Smoking, postmenopausal hormone therapy and the risk of venous thrombosis: a population‐based, case–control study

In postmenopausal women, oral hormone therapy (HT) is responsible for more than two venous thrombosis (VT) events per 1,000 person-years of treatment (Rossouw et al, 2002). Recent evidence supports a synergistic effect of smoking and oral contraceptives on the risk of VT (Pomp et al, 2008). Because HT has similar components as oral contraceptives – oestrogen progestogen, albeit in lower doses - smokers could represent a group in whom the VT risk associated with HT is considerably increased. Although no interaction between smoking and HT was found in the Women’s Health Initiative (WHI) clinical trial (Cushman et al, 2004), the small number of smoking VT cases and the selection of healthy participants in that trial may limit the validity and generalizability of this null finding. Our aim was to investigate the presence of this interaction in a large population-based study.

The impact of endocrine therapy on sexual dysfunction in postmenopausal women with early stage breast cancer: encouraging results from a prospective study

The goal of this project was to investigate the contentious issue of a possible effect of endocrine therapy (ET) on sexual dysfunction (SD) in postmenopausal early stage breast cancer survivors. To date, few studies have assessed sexual functioning prior to initiating ET and none have taken sexual distress into account when reporting the prevalence of ET-induced SD. We report the findings of a study on the change in SD (defined as experiencing sexual problems causing distress) during the first 6 months of ET usage. Between January 2009 and May 2011, 118 patients entered the study and 66 completed questionnaires prior to initiation of ET and after 6 months of use. Sexual functioning (SF) was evaluated with the female sexual function index while sexual distress was assessed with the female sexual distress scale (FSDS-R). Gynecological symptoms were measured with the FACT-B ES subscale. Over time, the level of gynecological symptoms increased (p < 0.001), whereas no decline in SF was observed. The percentage of women who reported experiencing at least one sexual problem (85 %) and the percentage who were sexually distressed (30 %) remained the same across time. Importantly, the change in the prevalence of SD between baseline (24 %) and 6 months (29 %) was not statistically significant. Women experiencing SD at baseline were more likely to experience SD after 6 months of ET usage (OR = 7.4, 95 % CI = 1.5-36.9) than women who had no SD prior to initiating ET. The observation that SF remained stable across time is encouraging news. However, longer follow-up and the inclusion of women who were premenopausal at diagnosis are needed to determine the potential influence of extended duration of ET (e.g., at least 5 years) on SD. Further studies, including assessing the impact of early identification of patients at risk of developing SD and timely intervention, are warranted.

Hormonal risk factors and invasive epithelial ovarian cancer risk by parity

Background:Recent studies have suggested that several ovarian cancer risk factors differ by parity status, but these findings have not been confirmed. We evaluated whether known risk factors of ovarian cancer differ between nulliparous and parous women using data from two large prospective cohorts.Methods:Data from the National Institutes of Health-AARP Diet and Health Study and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were combined for this analysis. Cox regression models were used to estimate associations with ovarian cancer risk. Risk heterogeneity by parity status was assessed using likelihood-ratio tests.Results:Among the 125 437 women included in the analysis, there were 16 589 (13%) nulliparous women and 108 848 (87%) parous women. Of the 623 women diagnosed with invasive epithelial ovarian cancer, 102 (16%) were nulliparous and 521 (84%) were parous. While parity reduced ovarian cancer risk, no differences were found for other risk factors by parity. Among ever users of hormone therapy, body mass index suggestively increased the risk of ovarian cancer by 1.5-fold in nulliparous but not parous women (P-heterogeneity=0.08).Conclusion:While nulliparous women have higher ovarian cancer risk than parous women, our findings suggest that the relative effects of most other risk factors do not differ by parity.