Postmenopausal Status Research Articles

Rice Bran Supplementation Ameliorates Gut Dysbiosis and Muscle Atrophy in Ovariectomized Mice Fed with a High-Fat Diet.

Rice bran, a byproduct of rice milling, is rich in fiber and phytochemicals and confers several health benefits. However, its effects on gut microbiota and obesity-related muscle atrophy in postmenopausal status remain unclear. In this study, we investigated the effects of rice bran on gut microbiota, muscle synthesis, and breakdown pathways in estrogen-deficient ovariectomized (OVX) mice receiving a high-fat diet (HFD). ICR female mice were divided into five groups: sham, OVX mice receiving control diet (OC); OVX mice receiving HFD (OH); OVX mice receiving control diet and rice bran (OR); and OVX mice receiving HFD and rice bran (OHR). After twelve weeks, relative muscle mass and grip strength were high in rice bran diet groups. IL-6, TNF-α, MuRf-1, and atrogin-1 expression levels were lower, and Myog and GLUT4 were higher in the OHR group. Rice bran upregulated the expression of occludin and ZO-1 (gut tight junction proteins). The abundance of Akkermansiaceae in the cecum was relatively high in the OHR group. Our finding revealed that rice bran supplementation ameliorated gut barrier dysfunction and gut dysbiosis and also maintained muscle mass by downregulating the expression of MuRf-1 and atrogin-1 (muscle atrophy-related factors) in HFD-fed OVX mice.

Fulvestrant with or without anti-HER2 therapy in patients in a postmenopausal hormonal state and with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of data from the Safari study (JBCRG-C06).

The role of endocrine therapy in the treatment of patients in a postmenopausal hormonal state and with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer (AMBC) is unclear. We analyzed the data from 94 patients with ER-positive HER2-positive AMBC enrolled in the Safari study (UMIN000015168), a retrospective cohort study of 1072 ER-positive AMBC patients in a postmenopausal hormonal state who received fulvestrant 500 mg (F500): (1) to compare time to treatment failure (TTF) and overall survival (OS) by treatment group, and TTF by treatment line; (2) in patients who received endocrine therapy (including F500) or anti-HER2 therapy as initial systemic therapy before chemotherapy, to investigate relations between TTF for the first-line therapy or time to chemotherapy (TTC) and OS; (3) to investigate factors associated with OS. The TTF was longer in the patients treated with F500 as first- or second-line therapy (n = 20) than in those who received later-line F500 therapy (n = 74) (6.6 vs. 3.7 months; HR, 1.98; p = 0.014). In the 59 patients who received endocrine therapy or anti-HER2 therapy as initial systemic therapy before chemotherapy, those with TTC ≥3 years had longer median OS than those with TTC <3 years (10.5 vs. 5.9 years; HR, 0.32; p = 0.001). Longer TTC was associated with prolonged OS. In patients with ER-positive HER2-positive AMBC enrolled in the Safari study, TTF was longer in patients who received F500 as first- or second-line therapy. In patients who received chemotherapy-free initial systemic therapy, the prolonged OS in those with TTC ≥3 years suggests that this value may be a helpful cut-off for indicating clinical outcomes.

Prevalence, Risk Factors, and Impact on Life of Female Urinary Incontinence: An Epidemiological Survey of 9584 Women in a Region of Southeastern China.

To investigate the prevalence, risk factors, and impact on quality of life (QOL) of female urinary incontinence (UI) in a region of southeastern China. This cross-sectional study, conducted between June 2022 and March 2023, included 9584 women aged 20-70 years who completed a standardized questionnaire through face-to-face interviews. This sample size represents almost 10% of the population in the target area. The prevalence of female UI was found to be 24.8%, with stress UI being the most common subtype (12.7%), followed by mixed UI (8.0%) and urgency UI (4.1%). Notably, the prevalence of UI increased progressively with age and body mass index (BMI). The study also revealed several risk factors for UI, including urban residence, postmenopausal status, multiple vaginal deliveries, instrumental vaginal deliveries, previous delivery of macrosomia, and prior history of pelvic floor surgery as determined by multivariate analysis. Furthermore, the study showed that 89.5% of women who reported UI experienced varying degrees of negative impact on their QOL. The incontinence quality of life (I-QOL) scale had an average score of 79.70±19.03, which decreased with increasing severity of UI. Despite the adverse effects on QOL, only 20.6% of women with UI had sought medical help. UI is common among women in the survey area. UI has been observed to have varying degrees of adverse effects on the QOL of those affected, but most of them do not seek treatment for several reasons, highlighting the urgent need for health authorities to develop effective UI intervention strategies.

Long-term clinical significance of benign endometrial cells identified on routine cervical cytology in women aged more or equal to 45 years

Within the Bethesda System, the recommendation of describing benign-appearing endometrial cells (BECs) has changed over recent years. Since the 2014 revision, their presence in cervical cytology reports has been deemed essential, beginning with age 45. Recent studies have suggested rising the reporting age to 50 years. Does the presence of these cells necessitate further assessment? This retrospective cohort study included patients aged between 45 and 65 years in whom BECs were present on cervical cytology between January 2001 and December 2010, with a follow-up at 5 and 10 years. Women who had abnormal cervical cells or atypical endometrial cells on cervical cytology were excluded, as well as women with a history of cervical or endometrial cancer, or a history of hysterectomy and incomplete follow-up data. One hundred seventy-six women were included. Of these, 31% were postmenopausal of which 65% used hormonal substitution therapy. Twenty-eight percent presented with abnormal uterine bleeding at inclusion. During the follow-up period of 10 years, 87.5% had a normal gynecological follow-up and 11.4% underwent a hysterectomy for benign pathology. One percent (2 patients) had been diagnosed with endometrial malignancy, both presenting with postmenopausal bleeding and aged over 60 years. Our study confirmed that the presence of BECs is not a reason for concern when no additional clinical indicator is recognized, especially with normal ultrasonographic examination. Further invasive exploration may be controversial. If reporting BECs in cervical cytology continues, we strongly agree on rising the reporting age to 50 years or postmenopausal state.

Oxidized dietary lipids induce vascular inflammation and atherogenesis in post-menopausal rats: estradiol and selected antihyperlipidemic drugs restore vascular health in vivo

BackgroundThermoxidation of edible oil through deep fat frying results in the generation of several oxidized products that promote lipid peroxidation and ROS production when eaten. Consumption of thermoxidized oil in post-menopausal conditions where the estrogen level is low contributes to cardiovascular disease. This study evaluates the role of estradiol and antihyperlipidemic agents (AHD) in restoring the vascular health of ovariectomized (OVX) rats fed with thermoxidized palm oil (TPO) and thermoxidized soya oil (TSO) diets.MethodA total of 10 groups of rats (n = 6) were set up for the experiment. Group I (normal control) rats were sham handled while other groups were OVX to bring about estrogen deficient post-menopausal state. Group II (OVX only) was not treated and received normal rat chow. Groups III-X were fed with either TPO or TSO diet for 12 weeks and treated with estradiol (ETD) 0.2 mg/kg/day, atorvastatin (ATV) 10 mg/kg/day, and a fixed-dose combination of ezetimibe and ATV (EZE 3 mg/kg/day + ATV 10 mg/kg/day).ResultsPro-atherogenic lipids levels were significantly elevated in untreated TSO and TPO groups compared to OVX and sham, resulting in increased atherogenic and Coronary-risk indices. Treatment with Estradiol and AHDs significantly reduced the total cholesterol, triglycerides, low-density lipoprotein cholesterol as well as AI and CRI compared to untreated TSO and TPO groups, whereas TSO and TPO groups showed significant elevation in these parameters compared to Group I values. Moreover, aortic TNF-α levels were extremely elevated in the untreated TSO and TPO compared to Group I. TNF-α levels were significantly reduced in rats treated with AHDs and ETD. Localized oxidative stress was indicated in the aortic tissues of TSO and TPO-fed OVX rats by increased malondialdehyde and decreased glutathione, catalase, and superoxide dismutase levels. This contributed to a depletion in aortic nitric oxide. AHDs and ETD replenished the nitric oxide levels significantly. Histological evaluation of the aorta of TSO and TPO rats revealed increased peri-adventitia fat, aortic medial hypertrophy, and aortic recanalization. These pathologic changes were less seen in AHDs and ETD rats.ConclusionThis study suggests that ETD and AHDs profoundly attenuate oxidized lipid-induced vascular inflammation and atherogenesis through oxidative-stress reduction and inhibition of TNF-α signaling.

Prevalence of menopausal symptoms and severity related factors among mid-aged Paraguayan women as measured with the 10-item Cervantes Scale

Objective: To determine the prevalence of menopausal symptoms and factors related to severity in mid-aged women.Methods: Cross-sectional study in which 216 urban-living women from Asunción-Paraguay (40–60 years) were surveyed with the 10 item Cervantes Scale (CS-10) and a general questionnaire (personal and partner data).Results: Median (interquartile range [IQR]) age of the sample was 48 [9] years, 48.1% were postmenopausal, 8.8% used menopausal hormone therapy, 39.4% psychotropic drugs, 43.5% had hypertension, 6.5% diabetes, 51.9% abdominal obesity, and 89.3% had a partner (n = 193). A history of sexual abuse was present in 2.8%. Median total CS-10 score was 8.5 [9.75]. Overall, 93.3% (180/193) of women having a partner were sexually active, with a median coital frequency of 8 times per month. According to the CS-10, the three most prevalent menopausal symptoms were: aching in muscles and/or joints (70.8%), anxiety and nervousness (70.8%) and hot flashes/night sweats (54.2%). Factors associated with higher CS-10 scores were: female age and educational level, marital status, menopausal status, and marital sexual aspects. Partner educational level was inversely correlated (rho Spearman coefficient) with CS-10 total scores. However, multiple linear regression analysis found that higher total CS-10 scores (more severe menopausal symptoms) negatively correlated to coital frequency and positively correlated with peri- and postmenopausal status, parity, sedentary lifestyle and a history of sexual abuse.Conclusion: Menopausal symptoms in this mid-aged urban female Paraguayan sample were related to hormonal, sexual and other female aspects.

Regulation of Bone by Mechanical Loading, Sex Hormones, and Nerves: Integration of Such Regulatory Complexity and Implications for Bone Loss during Space Flight and Post-Menopausal Osteoporosis.

During evolution, the development of bone was critical for many species to thrive and function in the boundary conditions of Earth. Furthermore, bone also became a storehouse for calcium that could be mobilized for reproductive purposes in mammals and other species. The critical nature of bone for both function and reproductive needs during evolution in the context of the boundary conditions of Earth has led to complex regulatory mechanisms that require integration for optimization of this tissue across the lifespan. Three important regulatory variables include mechanical loading, sex hormones, and innervation/neuroregulation. The importance of mechanical loading has been the target of much research as bone appears to subscribe to the "use it or lose it" paradigm. Furthermore, because of the importance of post-menopausal osteoporosis in the risk for fractures and loss of function, this aspect of bone regulation has also focused research on sex differences in bone regulation. The advent of space flight and exposure to microgravity has also led to renewed interest in this unique environment, which could not have been anticipated by evolution, to expose new insights into bone regulation. Finally, a body of evidence has also emerged indicating that the neuroregulation of bone is also central to maintaining function. However, there is still more that is needed to understand regarding how such variables are integrated across the lifespan to maintain function, particularly in a species that walks upright. This review will attempt to discuss these regulatory elements for bone integrity and propose how further study is needed to delineate the details to better understand how to improve treatments for those at risk for loss of bone integrity, such as in the post-menopausal state or during prolonged space flight.

Association of reproductive risk factors and breast cancer molecular subtypes: a systematic review and meta-analysis

BackgroundAssociations between reproductive factors and breast cancer (BC) risk vary by molecular subtype (i.e., luminal A, luminal B, HER2, and triple negative/basal-like [TNBC]). In this systematic review and meta-analysis, we summarized the associations between reproductive factors and BC subtypes.MethodsStudies from 2000 to 2021 were included if BC subtype was examined in relation to one of 11 reproductive risk factors: age at menarche, age at menopause, age at first birth, menopausal status, parity, breastfeeding, oral contraceptive (OC) use, hormone replacement therapy (HRT), pregnancy, years since last birth and abortion. For each reproductive risk factor, BC subtype, and study design (case–control/cohort or case-case), random-effects models were used to estimate pooled relative risks and 95% confidence intervals.ResultsA total of 75 studies met the inclusion criteria for systematic review. Among the case–control/cohort studies, later age at menarche and breastfeeding were consistently associated with decreased risk of BC across all subtypes, while later age at menopause, later age of first childbirth, and nulliparity/low parity were associated with increased risk of luminal A, luminal B, and HER2 subtypes. In the case-only analysis, compared to luminal A, postmenopausal status increased the risk of HER2 and TNBC. Associations were less consistent across subtypes for OC and HRT use.ConclusionIdentifying common risk factors across BC subtypes can enhance the tailoring of prevention strategies, and risk stratification models can benefit from subtype specificity. Adding breastfeeding status to current BC risk prediction models can enhance predictive ability, given the consistency of the associations across subtypes.

Pelvic insufficiency fractures after intensity modulated radiation therapy combined with chemotherapy for cervix carcinoma: Incidence and impact of bone mineral density

Background and PurposeThe aim of this study was to evaluate the incidence and predictive factors of Pelvic Insufficiency Fractures (PIFs) occurring after Intensity Modulated Radiation Therapy (IMRT) combined with chemotherapy for locally advanced cervical cancer (CC).Material and methodsMedical records of patients receiving radio-chemotherapy with IMRT between 2010 and 2020 for advanced CC were reviewed. PIFs were detected during follow-up on pelvic Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). The cumulative incidence rate of PIFs and its confidence interval were calculated at 2 and 5 years of follow-up. Pre-therapeutic Bone Mineral Density (BMD) (g/cm3) was evaluated on CT simulation for sacrum and the fourth lumbar (L4) vertebrae. Sacrum dosimetric parameters (V30Gy, V40Gy, D50%, Dmean) were analyzed.Results136 patients were included. The median follow-up was 4.4 years. Median dose of D50% and V40Gy sacrum were 35.2 Gy (20.6–46.4) and 32.2% (7.2–73.4) respectively. The 2-year and 5-year cumulative incidence rates were 15.7% (95% CI: 9.88–22.71) and 22% (95% CI: 14.58–30.45) respectively. Median time interval between RT completion and PIFs’ detection was 11.5 months (IQR: 7.4–22.3). Univariate analysis showed that older age (p < 0.01), postmenopausal status at baseline (p < 0.01), and lower sacral and spinal BMD at baseline (respectively p < 0.001 and p < 0.01) were significantly associated to all sites of PIFs, and lower sacral BMD with sacral fractures (p < 0.001).ConclusionPost-IMRT PIFs were detected in 18.4% of patients with locally advanced CC. Individual predisposing factors as older age, postmenopausal status, decreased bone density on the CT simulation were mainly predictive.

Long-term outcomes of intraoperatively-placed applicator brachytherapy for rapid completion of breast conserving treatment: An analysis of a prospective registry data.

To evaluate the long-term outcome of accelerated partial breast irradiation utilizing intraoperatively placed applicator-based brachytherapy (ABB) in early-stage breast cancer. From our prospective registry, 223 patients with pTis-T2, pN0/pN1mic breast cancer were treated with ABB. The median treatment duration including surgery and ABB was 7days. The prescribed doses were 32Gy/8 fx BID (n=25), 34Gy/10 fx BID (n=99), and 21Gy/3 fx QD (n=99). Endocrine therapy (ET) adherence was defined as completion of planned ET or≥80% of the follow-up (FU) period. Cumulative incidence of ipsilateral breast tumor recurrence (IBTR) was estimated and influencing factors for IBTR-free survival rate (IBTRFS) were analyzed. 218/223 patients had hormone receptor-positive tumors, including 38 (17.0%) with Tis and 185 (83.0%) with invasive cancer. After a median FU of 63months, 19 (8.5%) patients had recurrence [17 (7.6%) with an IBTR]. Rates of 5-year IBTRFS and DFS were 92.2% and 91.1%, respectively. The 5-year IBTRFS rates were significantly higher for post-menopausal women (93.6% vs. 66.4%, p=0.04), BMI<30kg/m2 (97.4% vs. 88.1%, p=0.02), and ET-adherence (97.5% vs. 88.6%, p=0.02). IBTRFS did not differ with dose regimens. Postmenopausal status, BMI<30kg/m2, and ET- adherence predicted favorable IBTRFS. Our results highlight the importance of careful patient selection for ABB and encouragement of ET compliance.

Endocrinology for the hepatologist.

Endocrinology for the hepatologist.

P-584 Treatment of benign uterine bleeding in morbidly obese postmenopausal women with an aromatase inhibitor

Abstract Study question Can morbidly obese women with postmenopausal bleeding, a benign endometrial biopsy, and no response to an oral progestin be successfully treated using an aromatase inhibitor? Summary answer Postmenopausal uterine bleeding in morbidly obese women with benign endometrial histology and an elevated serum estrone level do respond to treated with an aromatase inhibitor. What is known already Morbidly obese postmenopausal women who have uterine bleeding and a benign endometrial biopsy are commonly not good surgical candidates, and need good medical treatment options especially when treatment with an oral progestin has failed. The etiology for uterine bleeding in these individuals can stem from elevated estrogen production from peripheral sources. Study design, size, duration This was a prospective, proof of concept study with no placebo control group. Ten morbidly obese postmenopausal women with elevated serum estrone levels and uterine bleeding for &amp;gt; eight weeks who had failed oral progestin therapy were treated with letrozole 2.5 mg/d and evaluated monthly for 3 months duration. At the first monthly follow-up visit, serum estrone levels were re-assessed. Vaginal bleeding was re-assessed at each monthly follow-up visit. Participants/materials, setting, methods This study was performed in an outpatient setting at a private health system. Inclusion criteria included postmenopausal uterine bleeding (not spotting), age &amp;gt; 50, postmenopausal status (based on an FSH level of &amp;gt; 40 mIU/mL and an estradiol &amp;lt; 25 pg/mL), an estrone level &amp;gt; 30 pg/mL, a BMI &amp;gt; 40 kg/m2, a benign endometrial biopsy, a normal pelvic ultrasound, and failure of progestin therapy. All women received letrozole 2.5 mg/d and were evaluated monthly. Main results and the role of chance Ten women were enrolled in the study. Their ages ranged from 51 to 68. Their mean BMI was 50.75 kg/m2. All of the women in the study had daily vaginal bleeding for &amp;gt; 8 weeks that was greater than spotting, and had additional co-morbidities that made them poor surgical candidates. Serum estrone levels pre-treatment ranged from 63 pg/mL to 550 pg/mL with a mean of 216 pg/mL. After 4 weeks of treatment with letrozole, 8 women had complete cessation of their vaginal bleeding which was sustained for the complete 3 months of follow-up. The two other women in the study had significantly reduced vaginal bleeding from treatment month one to 3 based on self-reporting. Serum estrone levels after 4 weeks of treatment with letrozole dropped by an average of 71% with a range of 50% to 93%. There were no serious adverse events, and no treatment tolerability complaints. Since there was no control group for comparison, the reductions in both vaginal bleeding and serum estrone levels could be from chance alone, including regression to the mean, and not treatment related. Limitations, reasons for caution This was a small, proof of concept study that was performed in a select population of patients. Although a very favorable outcome was obtained in our study population, a much larger study might show both a reduced success rate in regards to vaginal bleeding and some significant adverse events. Wider implications of the findings The data from this study suggests that morbidly obese postmenopausal women with uterine bleeding and benign endometrial histology who have failed oral progestin therapy, are poor surgical candidates, and in whom IUD placement may be very difficult, may have another good treatment option. Trial registration number N/A

1422-P: The Impact of Type 2 Diabetes Mellitus on the Clinical Outcome of Breast Cancer

Objectives: Women with breast cancer and diabetes have worse outcomes than those with breast cancer without diabetes. The objective of this study was to investigate the impact of pre-existing diabetes on breast cancer prognosis. Methods and Materials: This was a retrospective observational study using Cancer database from a single tertiary center. The study population included women aged ≥20 years with breast cancer diagnosed between 1 January 2014 and 31 December 2018. Patients were categorized by diabetes status (T2D: n=111, non-T2D: n= 889). The clinicopathological features and outcomes were collected and compared between women with and without diabetes. Cox proportional hazard regression was used to estimate adjusted hazard ratios for overall mortality. Results: Compared to non-T2D patients, T2D patients were significantly older, had higher BMI, were more post-menopausal state at breast cancer diagnosis, had more comorbid conditions, and were in lower educational states. There were no statistically significant differences in tumor characteristics, including metastasis, lymph nodes, grade, and extent of surgery. Women with T2D had a significantly increased risk of overall mortality after adjusting for demographic and traditional risk factors for breast cancer (HR=2.15; 95%CI=1.10-4.20). Compared to patients with pre-existing T2D (n=111), patients with newly diagnosed T2D after receiving a breast cancer diagnosis (n=34) had a lower risk of breast cancer recurrence (HR=0.30; 95%CI=0.10-0.94). Conclusion: Our study showed that pre-existing T2D and T2D itself increase the risk of recurrence and total mortality among patients with breast cancer. These findings provide important prognostic information for the treatment of women with both T2D and breast cancer. Therefore, diabetes deserves additional attention to assess possible causal relationships that potentially could be modified to improve outcomes. Disclosure Y.Kim: None. I.Goak: None. H.Jin: None. T.Park: None. K.Lee: None.

Association of reproductive factors and exogenous hormone use with distal sensory polyneuropathy among postmenopausal women in the United States: results from 1999 to 2004 NHANES

Postmenopausal status is a risk factor for distal sensory polyneuropathy—the most common type of peripheral neuropathy. We aimed to investigate associations between reproductive factors and history of exogenous hormone use with distal sensory polyneuropathy among postmenopausal women in the United States using data from the National Health and Nutrition Examination Survey 1999–2004, and to explore the modifying effects of ethnicity on these associations. We conducted a cross-sectional study among postmenopausal women aged ≥ 40 years. Women with a history of diabetes, stroke, cancer, cardiovascular disease, thyroid disease, liver disease, weak or failing kidneys, or amputation were excluded. Distal sensory polyneuropathy was measured using a 10-g monofilament test, and a questionnaire was used to collect data on reproductive history. Multivariable survey logistic regression was used to test the association between reproductive history variables and distal sensory polyneuropathy. In total, 1144 postmenopausal women aged ≥ 40 years were included. The adjusted odds ratios were 8.13 [95% confidence interval (CI) 1.24–53.28] and 3.18 (95% CI 1.32–7.68) for age at menarche < 11 years and time since menopause > 20 years, respectively, which were positively associated with distal sensory polyneuropathy; adjusted odds ratios were 0.45 for the history of breastfeeding (95% CI 0.21–0.99) and 0.41 for exogenous hormone use (95% CI 0.19–0.87) were negatively associated. Subgroup analysis revealed ethnicity-based heterogeneity in these associations. Age at menarche, time since menopause, breastfeeding, and exogenous hormone use were associated with distal sensory polyneuropathy. Ethnicity significantly modified these associations.

Postmenopausal Status Exacerbates Stress-Related Neurological Disorders in Rats

Aims: This study was aimed at assessing the effects of social instability stress (SIS) and immobilization stress (IS) in postmenopausal (PM) conditions. Postmenopause is a physiological state often associated with mild neuronal disorders (NDs) such as anxiety and irritability. The aging of the worldwide population, coupled with multiple stressors, can lead to significant public health concerns, including severe NDs.&#x0D; Place and Duration of Study: Tests and analyses were carried out within the confines of the Laboratory of Animal Physiology of the University of Yaoundé I (Cameroon) for 3 months. &#x0D; Study Design: To induce PM syndrome, an 84-day ovariectomized Wistar rat model was used.&#x0D; Methodology: Random sampling of 4 groups of 6 rats, each aged between 8 and 10 weeks, was used. SIS and IS were induced during PM installation. Behavioral status, biochemical, and histopathological analyses were carried out.&#x0D; Results: SIS combined with IS exacerbates NDs induced by low estrogen levels. Furthermore, ovariectomized stressed rats are more depressed and anxious than the control. They presented severe hippocampal inflammation, oxidative stress, and memory impairment owing to low levels of ACh and reduced neuronal expression in the hippocampus. Overall, PM status makes NDs linked to stress worse in rats.&#x0D; Conclusion: Stress promotes oxidative stress, neuroinflammation, and neuronal death, leading to greater affective and cognition disorders when estrogen levels are low. Thus, there is a need to focus on the management of stress during menopausal life.

Correlation of background parenchymal enhancement on breast MRI with breast cancer

To evaluate the prognostic value of background parenchymal enhancement (BPE) in breast magnetic resonance imaging (MRI) in women referred to radiological department as a high risk for breast cancer. A retrospective, cross-sectional study included 327 consecutive patients (mean age: 60 years, age range: 30-90 years) who underwent breast MRI and tissue biopsy between 2007 and 2016. All MRI images (T1, T2, and subtraction images) were evaluated visually. The relationship of BPE with patient age, fibroglandular tissue (FGT), Breast Imaging Reporting and Data System (BIRADS) categories, presence of breast cancer, and expression of human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), oestrogen receptor (ER), and Ki67 were analysed. Furthermore, all variables were correlated with pre- and postmenopausal status. BPE of bilateral breast showed a weak correlation with FGT (right BPE: r=-0.14, p=0.004; left BPE: r=0.16, p=0.003), a weak negative correlation with patient age (right BPE: r=-0.14, p=0.007; left BPE: r=-0.15, p=0.006), and significant correlation with HER2 (right BPE, p=0.02), left BPE with HER2 was not significant. Among the correlations between BPE and BIRADS, only between right BPE and right BIRADS was significant (p=0.031). No clear evidence of an association between breast MRI BPE and breast cancer in premenopausal and postmenopausal status was observed, and no difference was found between the right and left breasts. The results of the present study showed no significant correlations between BPE and breast cancer. In addition, there was no significant difference between the right and left breast. Hence, BPE of MRI may not be a reliable biomarker of breast cancer development.

Associations between body mass index with cancer recurrence and all-cause mortality among survivors of breast cancer.

12074 Background: It is widely recognized that obesity is associated with increased breast cancer incidence. While body mass index (BMI) does not capture measures of body composition, it is routinely collected during clinical care. However, we do not know whether BMI at breast cancer diagnosis affects cancer recurrence or all-cause mortality. This study aims to investigate the associations between clinical categories of BMI, cancer recurrence, and all-cause mortality in this population. Methods: All breast cancer survivors treated at Northwestern Medicine on or after 1/1/2005 were included. We applied the WHO classification of BMI (kg/m2): underweight ( &lt; 18.5), normal (18.5-24.9), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (≥ 40). Cox proportional hazards models were used to determine the associations between BMI category at baseline and cancer recurrence plus all-cause mortality for breast cancer survivors. Models were adjusted for potential confounders including age, gender, race, ethnicity, histological grade, clinical stage, chemotherapy use, smoking, alcohol use, history of coronary artery disease, and history of Diabetes Mellitus. Results: Among all the 20,322 breast cancer survivors, 1,371 all-cause deaths and 1,183 cancer recurrences were observed. For patients aged 55 and above at diagnosis, there were 964 deaths and 632 cancer among 11,818 cases. When compared with a normal BMI (18.5-24.9), a BMI of 40 and above is associated with a higher risk of all-cause mortality among stage 1 breast cancer survivors (HR 1.90, 95 % CI 1.17-3.09), whereas a BMI of lower than 18.5 is associated with a higher risk of all-cause mortality among stage 4 breast cancer patients (HR 3.21, 95 % CI 1.24-8.30). For cancer recurrence, when compared with a normal BMI (18.5-24.9), a BMI of 40 and above is associated with a higher risk of cancer recurrence among stage 0 breast cancer survivors (HR 3.78, 95 % CI 1.21-11.81) and a BMI of 35 to 39.9 is associated with a higher risk of cancer recurrence among stage 3 breast cancer patients (HR 1.91, 95 % CI 1.01-3.61). We did not observe effect modification for either association by age at diagnosis using a cut-point of 55 years, which is considered as reaching postmenopausal status. Conclusions: Higher levels of obesity are associated with a higher mortality risk among early-stage breast cancer survivors whereas underweight is associated with a higher mortality risk for terminal-stage breast cancer. The associations between high-class obesity and increased risk of cancer recurrence were observed among stage 0 and stage 3 breast cancer survivors. These findings emphasize the importance of BMI as a tool for monitoring the health of breast cancer survivors. However, further study is needed to better understand the impact of BMI, and more importantly body composition, on the health and longevity of breast cancer survivors.

The impact of 4R Care Delivery Model on timing and sequence of bone density screening among breast cancer patients.

e24061 Background: Bone loss is common in patients with breast cancer and can impact treatment decisions related to endocrine therapy. Hence, bone density assessment prior to start of endocrine therapy is highly important, especially because endocrine therapy is recommended as the first line of adjuvant treatment in patients with ER+ breast cancer. However, implementing bone density assessment in a timely manner is challenging, particularly early in the care trajectory, which involves many specialties and includes many other tests and procedures. We conducted a care delivery optimization in a large health system to implement bone density testing and referral for bone health consultation prior to endocrine therapy. The optimization was conducted as part of implementing the 4R Oncology model (Right Info, Right Care, Right, Right Patient, at the Right Time), a novel approach to optimizing patient-facing care planning, team-based delivery and patient self-management. Here we describe the impact of this optimization. Methods: A cohort of 278 women with breast cancer who were in the 4R intervention (the 4R cohort) was compared to a historical control cohort of 201 women who received care pre-4R. Demographic, bone health history, and oncologic care data were abstracted from chart review and clinical databases. The prevalence of bone loss and timing of bone density consultation request was compared between the 4R and historical control cohorts. Results: The age, race/ethnicity and rate of ER+ cancer were similar between the cohorts. Patients in the 4R cohort were significantly more likely than those in the control cohort to have received a consultation for bone density screening prior to the start of endocrine therapy. They were also more likely to receive a bone density test result during their care. These findings remained significant when data were restricted to those ≥ 50 years (as a proxy for postmenopausal status) and those with ER-positive breast cancer. The rates of osteopenia and osteoporosis were similar between the cohorts: control 47%, 24%; 4R cohort: 46%, 23% respectively (data not shown). Conclusions: Care optimization using the 4R Oncology Model was associated with a significant improvement in the timing of bone density test before initiation of endocrine therapy. The 4R Oncology Model can lead to more informed decision making in adjuvant endocrine therapy for patients with breast cancer. Additional optimizations to improve the rates of bone density tests and referrals will be beneficial. [Table: see text]

Androgen Receptor Expression in ER and PR Negative Breast Cancer—A Study from a Tertiary Hospital in Northern India

Objectives Breast cancer is the leading cause of cancer-related deaths in women. Estrogen (ER) and progesterone receptor (PR) status and Her2 overexpression are major determinants in therapeutic decision making. Triple-negative breast cancers (TNBCs) have limited treatment options. Androgen receptor (AR) expression opens up therapeutic avenues for these patients. The aim of this article was to study the immunohistochemical expression of ARs in ER and PR Negative breast carcinomas and to correlate AR expression with various clinical, histopathological, and other immunohistochemical parameters.Materials and Methods It is a cross-sectional study including 105 ER and PR Negative cases of breast carcinoma. Clinical parameters, histopathology, and immunohistochemical expression of AR, Her2, and Ki67 were analyzed in all cases.Results AR expression was observed in 63.8% of ER and PR Negative breast cancers. In this group, AR expression was strongly associated with Her2 co-expression (89.2%) as compared to TNBCs (45.8%); p-value = 0.0002. Significant correlation was also observed between AR expression and tumor necrosis (p-value = 0.034) and postmenopausal status (p = 0.007).Conclusion Our study shows that significant proportion of ER and PR Negative breast carcinomas (ER- PR- Her2+ and TNBCs) show AR expression. We strongly recommend routine evaluation of all hormone receptor-negative breast carcinomas for AR status by immunohistochemistry.

Chronic arthritides and bone structure: focus on rheumatoid arthritis-an update.

Normal bone remodeling depends of a balance between bone forming cells, osteoblasts and bone resorbing cells, the osteoclasts. In chronic arthritides and some inflammatory and autoimmune diseases such as rheumatoid arthritis, there is a great constellation of cytokines produced by pannus that impair bone formation and stimulate bone resorption by inducing osteoclast differentiation and inhibiting osteoblast maturation. Patients with chronic inflammation have multiple causes that lead to low bone mineral density, osteoporosis and a high risk of fracture including circulating cytokines, impaired mobility, chronic administration of glucocorticoids, low vitamin D levels and post-menopausal status in women, among others. Biologic agents and other therapeutic measures to reach prompt remission might ameliorate these deleterious effects. In many cases, bone acting agents need to be added to conventional treatment to reduce the risk of fractures and to preserve articular integrity and independency for daily living activities. A limited number of studies related to fractures in chronic arthritides were published, and future investigation is needed to determine the risk of fractures and the protective effects of different treatments to reduce this risk.