History Of Hormone Replacement Therapy Research Articles

Potential benefits of hormone replacement therapy on cardiovascular and kidney outcomes in postmenopausal women with chronic kidney disease.

Hormone replacement therapy (HRT) is recommended for alleviating vasomotor symptoms or preventing bone loss in postmenopausal women. This study aimed to investigate the impact of hormone replacement therapy on major adverse cardiovascular events, kidney failure, and mortality in women with chronic kidney disease (CKD). This population-based cohort study analyzed data from the National Cancer Screening Program and the national health examination of South Korea. Data on postmenopausal women were extracted from the 2009 National Cancer Screening Program. Among these postmenopausal women, those with CKD without kidney replacement therapy were selected through a national health examination from 2009 to 2013. The study outcomes were the risks of major adverse cardiovascular events, kidney failure, and all-cause mortality according to hormone replacement therapy. A total of 768,279 postmenopausal women with CKD were enrolled in this study; of these women, 13.8% (N = 106,052) had a history of hormone replacement therapy. The user and non-user groups differed with respect to baseline characteristics, with the latter being older and having risk factors for cardiovascular disease. After adjustment for confounding factors, the group exposed tohormone replacement therapyshowed lower risks of major adverse cardiovascular events, kidney failure, and all-cause mortality. This study suggests the potential benefits of hormone replacement therapy in postmenopausal women with CKD and highlighted its potential advantages for cardiovascular and kidney outcomes.

9342 Managing Osteoporosis In Patients With Phocomelia: Challenges And Strategies

Abstract Disclosure: M. Renzu: None. C. Hubers: None. V. Mehta: None. A.M. Qazi: None. A.M. Satei: None. D.K. Yerasuri: None. Introduction: Phocomelia, a rare congenital limb malformation, often results from disruptions in limb bud formation during embryonic stage, due to genetic mutations, teratogens, or environmental factors like thalidomide embryopathy. These disruptions pose unique challenges in bone health management, including an increased risk of osteoporosis.We present a case report of a 52-year-old patient with phocomelia who developed an early onset severe osteoporosis. This case stresses the need for specific measures and care to tackle bone health in individuals with congenital limb anomalies. Case Presentation: A 52-year-old white female with phocomelia, had absence of the left forearm and hand, as well as a transverse tibial deficiency with a prosthetic left lower leg since the age of 1. Osteoporosis was diagnosed after follow-up, with initial osteopenia noted at age 49. DEXA scan showed lumbar osteopenia, radial osteoporosis, and bilateral femoral neck osteopenia. FRAX score showed an 11.9% risk of osteoporotic fracture and 3.1% risk of a hip fracture.Risk factors to her osteoporosis included late menarche, early menopause due to hysterectomy, and a history of hormone replacement therapy without pregnancies. Also, chronic colitis and diarrhea caused malabsorption issues. Her left hip bone mineral density was disproportionately low due to chronic prosthesis use, necessitating close monitoring and treatment initiation with Denosumab, along with vitamin D3 and calcium supplementation.As of the latest follow-up, the patient is closely monitored, and improvement is noted in her condition. She has incorporated daily gym sessions into her routine, indicating proactive engagement in her well-being. Discussion: Managing osteoporosis in patients with phocomelia needs a personalized approach, considering the patient's unique anatomical challenges and the limitations of traditional osteoporosis management strategies. Bone tissue adapts its structure based on mechanical loading, with reduced loading in deformed limbs leading to increased resorption and elevated osteoporosis risk. Tailored treatment plans, including Denosumab, which is known as an effective pharmacological option for managing osteoporosis, complemented by dietary adjustments to enhance vitamin D and calcium intake. Physical therapy programs play a vital role in muscle strengthening and balance improvement, reducing fracture risk.Another challenge that patients with phocomelia face is barriers to accessing healthcare services, like limited specialized care providers, financial constraints, and transportation difficulties, leading to increased morbidity. Hence early screening and intervention are essential to prevent osteoporotic complications. Overall, a comprehensive approach to osteoporosis management in phocomelia patients is crucial for optimizing outcomes and enhancing quality of life. Presentation: 6/3/2024

12434 History Of Surgical Menopause Is Associated With An Accelerated “Adrenal Aging” In Menopausal Women

Abstract Disclosure: J. Saini: None. R. Nathani: None. J. Larson: None. V. Fell: None. I. Bancos: None. Background: Surgical menopause due to bilateral salpingo-oophorectomy (BSO) at a younger age is associated with an increased risk of cardiovascular disease, cognitive decline, and increased mortality. Aging is associated with abnormalities in steroid metabolome, most notably an increased glucocorticoid to androgen ratio (“adrenal aging”). We hypothesized that in postmenopausal women of the same age, the duration of menopause is associated with adrenal aging. Objective: To determine the differences in the adrenal steroid metabolome of women with a history of BSO as compared to age-matched women following natural menopause. Methods: We conducted a single-center cross-sectional study in postmenopausal women with or without a history of BSO, between December 2020 to December 2022 Each participant collected 24-hour urine, which was analyzed for steroid profiling by liquid chromatography-tandem mass spectrometry (25 steroids). Exclusion criteria were inability to collect a 24h urine sample, exogenous glucocorticoid use, advanced malignancy, and chronic opioid use. Primary endpoints were glucocorticoid/androgen ratio, 11β-hydroxysteroid dehydrogenase type 2 activity (cortisol/cortisone, Tetrahydrocortisol (THF) + 5 α-tetrahydrocortisol (5 α-THF)/ Tetrahydrocortisone, THE) and 5 α-reductase type activity (Tetrahydrocortisol (THF)/5 α-tetrahydrocortisol (5 α-THF) and Etiocholanolone/Androsterone, Et/An). Results: A total of 245 women were enrolled: 124 women (median age of 66 years, IQR 63-72) with a history of BSO and 121 women (median age of 68 years, IQR 64-71) who underwent natural menopause (P=0.214). Median age at menopause was 44 years (IQR 41-46) in the BSO group, and 50 years (IQR 48-53) in the natural menopause group. History of hormone replacement therapy with estrogen was reported in 161 (66%) women, more frequently (92% vs 39%, P<0.001) and for a longer duration (median 12 years (IQR 6-16) vs 6 years (IQR 3-9), P<0.001) in in the BSO group, as compared to the natural menopause group. Although both groups had similar levels of urinary androgens (median 1387 vs 1686 mcg/24h, P=0.063) and total glucocorticoids (median 10877 vs 10277 mcg/24h, P=0.354), women with a history of BSO demonstrated a higher glucocorticoid/androgen ratio (median 7.9 (IQR 5.0-11.1) vs 6.7 (4.3-9.9), P=0.014), and a lower Et/An ratio (median 1.4 vs 1.6, P=0.045), but not THF/5aTHF ratio (median 1.7 vs 1.8, P=0.380) in comparison to women with natural menopause. No differences were found in other ratios. Conclusion: Women with a history of BSO demonstrated a higher glucocorticoid/androgen ratio in comparison to women undergoing natural menopause, suggestive of BSO-induced accelerated “adrenal aging”. Future studies need to examine associations between the abnormal steroid metabolome and increased cardiovascular morbidity, frailty, and mortality reported following BSO. Presentation: 6/3/2024

Correlation between serum vitamin D levels and bone mass density evaluated by radiofrequency echographic multi-spectrometry technology (REMS) in menopausal women.

Osteoporosis is a common condition associated with an increased risk of bone fractures due to fragility. Bone mineral density (BMD) is lower in menopausal women due to estrogen deficiency, age-related decline in osteoblast function, decreased calcium absorption, and reduced synthesis of vitamin D, which lead to osteoporosis. The aim of this study was to determine the correlation between serum vitamin D levels and BMD assessed using radiofrequency echographic multi-spectrometry technology (REMS) in menopausal women. A cross-sectional study was conducted at Prof. Dr. Chairuddin P. Lubis Hospital of Universitas Sumatera Utara, Medan, Indonesia, from May 2023 to August 2023. Consecutive sampling method was employed to sample menopausal women with no history of hysterectomy or oophorectomy (unilateral or bilateral), and no history of hormone replacement therapy or vitamin D supplementation. Interviews and physical examinations were conducted to obtain the characteristics of the subjects (age, duration of menopause, and body mass index). The 25(OH)D level was measured using immunoassay and REMS examination was conducted to assess BMD. The Spearman correlation test was used to assess the correlation between serum vitamin D levels and BMD. A total of 32 menopausal women were included in this study with the average vitamin D level was 18.05±5.81 ng/mL, and the mean BMD level was -2.13±1.23. The data showed a significant positive correlation between serum vitamin D levels and BMD in menopausal women (r=0.710; p=0.020). This study highlights that REMS could be useful as an alternative to dual-energy x-ray absorptiometry (DXA) to assess DMD in postmenopausal women.

Risk factors for 5-year complications after midurethral sling surgery for stress urinary incontinence: a retrospective cohort study from Taiwan

Midurethral sling surgery is the current gold standard worldwide for stress urinary incontinence (SUI) surgery, with over 90% of surgeons worldwide using the midurethral sling for SUI between 2008 and 2018. However, concerns surround mesh-related adverse events associated with the midurethral sling. The decision to use the midurethral sling for surgical treatment has become a challenging one for clinicians, surgeons and patients. We sought to determine the factors for 5-year complications after midurethral sling surgery, to improve the clinical decision-making process. Records were reviewed from a total of 1961 female patients who underwent their first midurethral sling surgery for SUI between 2003 and 2018 at a single teaching hospital in Taiwan. A multivariable Cox proportional hazard model calculated the hazard ratios of risk factors for surgical complications, after adjusting for confounders. Surgical complications (i.e., secondary surgery and urinary retention) occurred in 93 (4.7%) patients within 5 years following the index operations. These patients were more likely to be older, to have a history of menopausal syndrome within 1 year prior to the index operation, a medication history of oral antidiabetic drug use, hormone replacement therapy (HRT), slower average flow rate, and longer voiding time compared with patients without surgical complications. In the multivariate analysis, HRT (adjusted hazard ratio, 1.787; 95% confidence interval, 1.011–3.158, p = 0.04) was significantly associated with surgical complications at 5 years, after adjusting for age, gender, diabetes, menopause syndrome, average flow rate, and sling type. Our findings suggest that a medication history of HRT may be a risk factor associated with surgical complications, especially urinary retention, at 5 years in women undergoing midurethral sling surgery for SUI.

Assessment of Cranial Sexual Dimorphism Using 3D Reconstruction: Implications for Gender-Affirming Surgery.

As more centers offer gender-affirming procedures, dissemination of best practices is critical to ensuring quality care. This study is the first to use advanced 3-dimensional visualization software to characterize cranial differences between natal males and females, as they relate to planning for facial gender-affirming operations. A retrospective analysis was conducted on randomly selected patients with facial computed tomography imaging performed at a single institution between February 2020 and July 2021. Patients with acquired bony deformity on computed tomography or documented history of hormone replacement therapy were excluded. The images were retrieved and analyzed using advanced 3-dimensional visualization software (Vitrea). Independent sample t tests were performed to analyze variation in typically sexually dimorphic facial features between natal males and females. We identified 50 patients (25 natal males and 25 natal females) who met the inclusion criteria. Ages ranged from 19 to 91. Natal males were found to have significantly greater frontosellar distances (difference between means, SEM: 2.7±1.2; P =0.03) and mandible volumes (difference between means, SEM: 14.0±4.2; P =0.002) than natal females. Statistical analysis revealed no significant differences in gonial angle, chin width, nasofrontal angle, or nasolabial angle between natal males and females. In this diverse sample of natal males and females, statistical analysis revealed that the sexually dimorphic facial characteristics most relevant to the planning of facial gender-affirming surgery are frontosellar distance and mandible volume. When planning facial gender-affirming surgery, we recommend that these characteristics be considered to achieve optimum results.

Hormone Replacement Therapy and Psoriasis Risk: A Nationwide Population-Based Cohort Study.

Hormone replacement therapy (HRT) is used to relieve menopause symptoms, but has been reported to be associated with coronary heart disease and cancers in women. However, a link between HRT and psoriasis has yet to be established. The aim of this study was to determine the association between HRT and the risk of psoriasis. We executed a nationwide population-based study. A total of 1,130,741 post-menopause women were enrolled in the national health care insurance database based on the enrollment criteria. The study population was classified into four groups based on the duration of the HRT, and the risk of psoriasis was analyzed. The incidence rates of psoriasis per 1,000 person-years were 3.36 and 4.09 in the no history of HRT and ≥ 5 years of HRT, respectively. After adjustment for age, smoking, alcohol intake, regular exercise, body mass index, diabetes mellitus, hypertension, and dyslipidemia, the most prolonged duration of the HRT group (≥ 5 years) exhibited significantly increased risk of developing psoriasis (hazard ratio, 1.22; 95% confidence interval, 1.16-1.29). We propose that HRT in post-menopausal women is associated with an increased likelihood of psoriasis development.

The EMory BrEast imaging Dataset (EMBED): A Racially Diverse, Granular Dataset of 3.4 Million Screening and Diagnostic Mammographic Images.

Supplemental material is available for this article. Keywords: Mammography, Breast, Machine Learning © RSNA, 2023.

Performance of risk prediction models in breast cancer screening among women in Cyprus.

Tools that can predict breast cancer risk in women will have a significant impact on women and healthcare systems in low- and middle-income countries. We compared the performances of the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model, the International Breast Cancer Intervention Study (IBIS) model, and the Gail model in predicting breast cancer risk among women in Cyprus. We recruited 655 women from Dr Burhan Nalbantoglu Devlet Hastanesi Hospital in Lefkosa: 318 had breast cancer and 337 did not have breast cancer (hospital-based controls). We collected retrospective data from the hospital's medical records and interviews with the women after informed consent. Data collected included: age, age at diagnosis, age at menarche, menopausal status, presence of benign breast disease, breast cancer in relatives, BRCA-1 and BRCA-2 mutations, history of hormone replacement therapy, and breast density. We calculated the 5-year risk of breast cancer and the risk values were used to plot receiver operating curves. For the area under the curve (95% confidence interval, CI), sensitivity and specificity for the models were: BOADICEA 0.81 (95% CI: 0.77-0.84), 26.4% and 98.8%; IBIS 0.80 (95% CI: 0.77-0.84), 19.4% and 97.3%; and Gail 0.76 (95% CI: 0.73-0.80), 17.3% and 98.5%. The breast cancer risk prediction models performed similarly although on closer appraisal, the BOADICEA and IBIS models performed slightly better. These models are simple, appropriate, cost-effective, and non-invasive tools for identifying high-risk women in low- and middle-income countries who could benefit from mammography screening.

Early menopause is associated with increased risk of retinal vascular occlusions: a nationwide cohort study

This nationwide population-based cohort study evaluated the association between female reproductive factors and the incidence of retinal vein occlusion (RVO) and retinal artery occlusion (RAO) using data provided by the Korea National Health Insurance Service. A total of 2,289,347 postmenopausal women over 50 years of age who participated in both national health screening and cancer screening in 2013 or 2014 were included. Data on female reproductive factors, including age at menarche, age at menopause, parity, history of hormone replacement therapy, and oral contraceptive pill usage, were collected. Patients were followed up until December 2018, and incident cases of RVO and RAO were identified using registered diagnostic codes from claim data. During an average follow-up period of 4.90 years, 7461 and 1603 patients were newly diagnosed with RVO and RAO, respectively. In the multivariable-adjusted Cox proportional hazard model, patients who experienced menopause after 55 years of age had a lower risk of RVO and RAO development compared to those who had menopause before 45 years of age, with a hazard ratio (95% confidence interval) of 0.83 (0.76–0.95) for RVO and 0.80 (0.66‒0.98) for RAO. In conclusion, early menopause was an independent risk factor for future development of RVO and RAO.

Association of Postmenopausal Bleeding with Endometrial Carcinoma

Aim: To find the association of postmenopausal bleeding with endometrial carcinoma. Study design: Cross-sectional analytical study Place and duration of study: Department of Obstetrics & Gynaecology, Sahiwal Teaching Hospital and Medical College, Sahiwal from 1st January 2019 to 31 December 2021. Methodology: One hundred women suffering from post-menopausal bleeding were enrolled. An endometrial biopsy was used for removing a piece of the tissue from the inner lining of the uterus and was conducted in suspicious women for confirming endometrial carcinoma by microscopic histopathological reporting.The frequency of endometrial carcinoma in post-menopausal women was analyzed. Results: The mean age was 56.2+0.5 years. The recurrent bleeding was observed in 7% cases and obesity was seen in 50 cases. Transvaginal ultrasonography was performed on women due to high suspicions. Out of the total 8 cases, 87.5% had a uterine thickness >5mm with no history of hormone replacement therapy. Incidence of endometrial carcinoma was 7% among postmenopausal women. Conclusion: Postmenopausal bleeding was commonly observed in obese women and in those who were on hormonal replacement therapy. Incidence of endometrial carcinoma was 7% in postmenopausal bleeding females. Keywords: Endometrial carcinoma; Women; Diagnosis; Developed countries

Quantifying diagnostic and etiologic management costs of perimenopausal abnormal uterine bleeding and postmenopausal bleeding

Quantifying diagnostic and etiologic management costs of perimenopausal abnormal uterine bleeding and postmenopausal bleeding

Relation Between Body Mass Index and Dry Eye Disease: The Japan Public Health Center-Based Prospective Study for the Next Generation.

To investigate the relation between body mass index (BMI) and dry eye disease (DED). We conducted a cross-sectional questionnaire-based survey in 85,264 Japanese men and women aged 40 to 74 years who participated in the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). Dry eye disease was defined as the presence of severe symptoms or clinical diagnosis. A multivariable logistic regression model was used to estimate the odds ratios (ORs) of DED associated with BMI and their two-sided 95% confidence intervals (CIs). We adjusted for age, cohort area, visual display terminal time, smoking status, alcohol intake, education status, income status, as well as history of hormone replacement therapy for women. Prevalence of DED was 23.4% (n = 19,985; 6,289 men, 13,696 women). Higher BMI was correlated with a lower prevalence of DED in a dose-response fashion, with an adjusted OR of DED (95% CI) per 1 kg/m2 increment of BMI of 0.98 (95% CI: 0.97-0.99) for men and 0.97 (95% CI: 0.97-0.98) for women. This large population-based study showed an inverse relationship between BMI and prevalence of DED in a Japanese population. Underestimation of DED is warned, especially for participants with high BMI.

A prolonged hiatus in postmenopausal HRT, does not nullify the therapy's positive impact on ageing related sarcopenia.

BackgroundPrevious work suggest a positive skeletal muscle effect of hormone replacement therapy (HRT) on skeletal muscle characteristics This study aimed to quantify any continued positive effect of HRT even after a sustained hiatus in treatment, controlling for two key muscle modulation hormones: Estradiol (E2) and Tri-iodo-thyronine (T3).Method and findingsIn 61 untrained women (18-78yrs) stratified as pre-menopausal, post-menopausal without (No_HRT) and post-menopausal with (Used_HRT) HRT history, body composition, physical activity, serum E2 and T3 were assessed by dual energy x-ray absorptiometry, Baecke questionnaire and ELISA. Gastrocnemius medialis (GM) and tibialis anterior (TA) electromyographic profiles (mean power frequency (mPowerF)), isometric plantar-flexion (PF) and dorsi-flexion (DF) maximum voluntary contraction (MVC), rate of torque development (RTD), isokinetic MVC and muscle volume, were assessed using surface electromyography, dynamometry and ultrasonography. Muscle quality was quantified as MVC per unit muscle size. E2 and E2:T3 ratio were significantly lower in postmenopausal participants, and were positively correlated with RTD even after controlling for adiposity and/or age. Pre-menopausal females had greater MVC in 8/8 PF and 2/5 DF (23.7–98.1%; P<0.001–0.049) strength measures compared to No_HRT, but only 6/8 PF (17.4–42.3%; P<0.001–0.046) strength measures compared to Used_HRT. Notably, Used_HRT had significant higher MVC in 7 PF MVC (30.0%-37.7%; P = 0.006–0.031) measures than No_HRT, while premenopausal and Used_HRT had similar uncorrected muscle size or quality. In addition, this cross-sectional data suggest an annual reduction in GM muscle volume corrected for intra-muscular fat by 1.3% in No_HRT and only 0.5% in Used_HRT.ConclusionEven years after cessation of the therapy, a history of HRT is positively associated with negating the expected post-menopausal drop in muscle quantity and quality. Whilst mPowerF did not differ between groups, our work highlights positive associations between RTD against E2 and E2:T3. Notwithstanding our study limitation of single time point for blood sampling, our work is the first to illustrate an HRT attenuation of ageing-related decline in RTD. We infer from these data that high E2, even in the absence of high T3, may help maintain muscle contractile speed and quality. Thus our work is the first to points to markedly larger physiological reserves in women with a past history of HRT.

Expression profiling revealed up-regulation of three lncRNAs in breast cancer samples.

Long non-coding RNAs (lncRNAs) have been vastly investigated for their critical roles in the pathogenesis of breast cancer. Yet, the expression pattern and clinical significance of three lncRNAs namely CTBP1AS2, LINC-ROR and SPRY4-IT1 in breast cancer are not completely clarified. In the present investigation, we assessed expression of these lncRNAs in breast cancer tissues and paired non-cancerous specimens from the same patients using quantitative real time PCR. Notably, expression of CTBP1AS2, LINC-ROR and SPRY4-IT1 were upregulated in breast cancer tissues compared with non-cancerous tissues (ER = 17.62, P value<0.000; ER = 4.62, P value = 0.001 and ER = 3.47, P value = 0.005, respectively). Relative expression of LINC-ROR in tumoral tissues compared with non-tumoral tissues was associated with a history of hormone replacement therapy (P = 0.04). Expression levels of CTBP1AS2, LINC-ROR and SPRY4-IT1 were significantly correlated with each other in both tumoral and non-tumoral tissues. The strongest correlations were detected between CTBP1AS2/ LINC-ROR and CTBP1AS2/ SPRY4-IT1 pairs in non-tumoral tissues. CTBP1AS2 and SPRY4-IT1 had the best sensitivity (80%) and specificity (64%) values, respectively. Based on AUC values, the best diagnostic power belonged to CTBP1AS2. The current study potentiates CTBP1AS2, LINC-ROR and SPRY4-IT1 as putative contributors in the pathogenesis of breast cancer and suggests these lncRNAs as candidates for functional analysis in this kind of cancer.

Association between Bone Metabolism and Vestibular Problems in the Modified Romberg Test: Data from the 2009-2010 Korean National Health and Nutrition Examination Survey.

Osteoporosis contributes to the occurrence of falling and vestibular problems, particularly in elderly patients. This study aimed to investigate the association between bone metabolism with vestibular problems and falling. A total of 4054 participants of the Korean National Health and Nutrition Examination Survey (KNHANES) from 2009 to 2010 aged ≥50 years old were surveyed on their history of falling, vestibular problems evaluated by the modified Romberg test, variables involving bone metabolism, and serum levels of vitamin D and alkaline phosphatase. They also underwent dual energy X-ray absorptiometry. The crude (simple) and adjusted odd ratios (ORs) of variables involving bone metabolism for vestibular problems in the modified Romberg test and falling were analyzed using a logistic regression model. A subgroup analysis was performed according to sex and the presence of menopause in females. Vestibular problems in the modified Romberg test group but not the falling group were associated with decreased serum vitamin D levels (p < 0.001; odds ratio (OR) = 0.951; 95% confidence interval (CI), 0.926–0.976). In subgroup analysis according to sex, the post-menopause group showed a higher rate of vestibular problems in the modified Romberg test compared to the pre-menopause group (4.5% vs. 0.7%, p = 0.019). In the post-menopause group, osteoporosis was positively associated with vestibular problems in the modified Romberg test (p = 0.001, OR = 10.971, 95% CI = 2.650–45.414). On the other hand, a history of hormone replacement therapy was negatively related with vestibular problems in this subgroup (p = 0.035; OR = 0.473; 95% CI = 0.239–0.948). A decrease in serum vitamin D levels may impact the vestibular system through neural signaling or by osteoporotic changes of the otic capsule, as well as otolith particles. Decreased estrogen levels in postmenopausal women may make them more prone to osteoporotic changes, which were associated with vestibular problems in the modified Romberg test. Because this is a cross-sectional study, the causal relationship of bone metabolism with vestibular function needs to be investigated.

A Multicentre Observational Study on Risk Factors for Breast Cancer.

Breast cancer is the most common malignancy in Indian women. There is scant data from Indian hospital-based populations on the prevalence of risk factors of this disease. We performed this study to quantify and analyze various epidemiological risk factors in Indian breast cancer patients. This was a multicenter collaborative study wherein breast cancer patients older than 18years were served a structured questionnaire after informed consent. Patients or their relatives were required to fill out the questionnaire and those who were unable to read and write were excluded. Data were abstracted from case record forms and variables were descriptively analyzed. Between January 2015 and February 2016, 800 patients were screened, of whom 736 patientswith a mean age of 50.13years were enrolled in the study. The mean number of pregnancies was 2.75 (0-11), the number (percentage) of women who had breastfed for more than 6months was 628 (85.3) and 406 (55.1%) patients were post-menopausal at the time of breast cancer diagnosis. Of the enrolled patients, 91 (12.8%) had history of exposure to passive smoke, 13 (1.8%) had partners who were heavy smokers, 27(3.7%) had history of oral contraceptive use, 4 (0.5%) had history of hormone replacement therapy, and 103 (14%) had undergone hysterectomy with oophorectomy. Our study contributes to the descriptive prevalence of some known risk factors in Indian breast cancer patients.

In silico identification of MAPK14-related lncRNAs and assessment of their expression in breast cancer samples

Mitogen-activated protein kinase (MAP kinase) pathways participate in regulation of several cellular processes involved in breast carcinogenesis. A number of non-coding RNAs including both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate or being regulated by MAPKs. We performed an in-silico method for identification of MAPKs with high number of interactions with miRNAs and lncRNAs. Bioinformatics approaches revealed that MAPK14 ranked first among MAPKs. Subsequently, we identified miRNAs and lncRNAs that were predicted to be associated with MAPK14. Finally, we selected four lncRNAs with higher predicted scores (NORAD, HCG11, ZNRD1ASP and TTN-AS1) and assessed their expression in 80 breast cancer tissues and their adjacent non-cancerous tissues (ANCTs). Expressions of HCG11 and ZNRD1ASP were lower in tumoral tissues compared with ANCTs (P values < 0.0001). However, expression levels of MAPK14 and NORAD were not significantly different between breast cancer tissues and ANCTs. A significant association was detected between expression of HCG11 and estrogen receptor (ER) status in a way that tumors with up-regulation of this lncRNA were mostly ER negative (P value = 0.04). Expressions of ZNRD1ASP and HCG11 were associated with menopause age and breast feeding duration respectively (P values = 0.02 and 0.04 respectively). There was a trend towards association between ZNRD1ASP expression and patients’ age of cancer diagnosis. Finally, we detected a trend toward association between expression of NORAD and history of hormone replacement therapy (P value = 0.06). Expression of MAPK14 was significantly higher in grade 1 tumors compared with grade 2 tumors (P value = 0.02). Consequently, the current study provides evidences for association between lncRNA expressions and reproductive factors or tumor features.

Expression analysis of vimentin and the related lncRNA network in breast cancer

Vimentin (VIM) is a mesenchymal marker which is expressed in some cancer types including breast cancer. A long non-coding RNA (lncRNA) has been identified to be transcribed from VIM gene locus and positively regulate expression of VIM. This lncRNA has been named as VIM-antisense 1 (VIM-AS1). Expression of VIM is also regulated by another lncRNA namely AGAP2-antisense RNA 1 (AGAP2-AS1). In the current study, we aimed at identification of the expression pattern of VIM, VIM-AS1, AGAP2 and AGAP2-AS1 in 78 breast cancer samples and their paired adjacent non-cancerous tissues (ANCTs) by means of real time PCR. All mentioned genes were significantly down-regulated in tumoral tissues compared with ANCTs (P values less than 0.000). Relative expression of VIM-AS1 in tumoral tissues versus ANCTs was associated with menopause age (P = .02) in a way that this gene was down-regulated in most of patients whose menopause age was between 40 and 50 years. Moreover, AGAP2–AS1 relative expression was associated with patients' body mass index (P = .03). There were trends toward association between VIM relative expression and tumor size (P = .07) and association between VIM-AS1 relative expression and obesity (P = .06). Expression of VIM was significantly higher in tumoral tissues of patients who had history of hormone replacement therapy compared with those without such history (P = .03). Moreover, expression levels of both VIM and AGAP2-AS1 were lower in patients whose menarche age was between 10 and 12 years old compared with those whose menarche age was between 13 and 15 years old (P values = .01 and 0.04, respectively). Transcript quantities of VIM, VIM-AS1, AGAP2 and AGAP2-AS1 were correlated with each other both in tumoral tissues and in ANCTs. Among four assessed genes, AGAP2 had the best diagnostic power for discrimination of tumoral tissues from ANCTs (AUC value = 0.87). Combination of four genes led to enhancement of AUC value to 0.94. The current study shows the importance of VIM and its associated lncRNAs in breast cancer and potentiates these genes as biomarkers for this malignancy. Moreover, these lncRNAs might be regarded as therapeutic targets in breast cancer.

744 Oestrogen as a Potential Shared Mechanism Between Medial Calcification and Intimal Atherosclerosis

Intimal atherosclerosis is a well-known cause of cardiovascular disease (CVD). Breast arterial calcification (BAC) is a form of medial arterial calcification and is a common incidental finding that is often thought to be clinically irrelevant on screening mammography. However, recent evidence suggests that BAC may be associated with CVD and cardiovascular risk factors. Menopausal status is also associated with CVD whereas history of hormone replacement therapy (HRT) use is inversely related to CVD. Our objective was to systematically review the available evidence for associations between BAC and menopausal status and HRT. PubMed and EMBED databases were searched up to February 2020 and reference lists of relevant papers were reviewed to identify additional papers. Study quality were graded and a random effects model was used to calculate a pooled OR and 95% CIs for the association of BAC and menopausal status and use of HRT. 16 observational studies were included representing a total of 34,757 women. Three of these were cohort and the rest were cross sectional studies. BAC was associated with menopausal status (OR 2.67; 95% CI 1.50–4.77) and inversely associated with the use of HRT (OR 0.57; 95% CI 0.40–0.80). BAC is associated with menopause and inversely associated with HRT. HRT and menopause are similarly associated with CVD, suggesting a shared hormonal mechanism between medial arterial calcification and intimal atherosclerosis.