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Baseline bone health status in multi-ethnic South African postmenopausal breast cancer patients at initiation of aromatase inhibitor therapy: A descriptive study.

ABSTRACT: INTRODUCTION:Osteoporosis (OP) risk factor assessment and bone mineral density (BMD) testing are frequently omitted at baseline in aromatase inhibitor (AI) studies, which may lead to misinterpretation of AI associated bone loss. The present study describes bone health of South African postmenopausal women of predominantly Mixed Ancestry, prior to AI treatment. METHODS:This descriptive baseline study, nested in a prospective AI cohort study, included postmenopausal women with endocrine sensitive breast cancer, aged 50 to 80 years. A baseline questionnaire documented demographic-, medical-, lifestyle- and fracture history. Body weight was assessed clinically, and body composition and BMD measured via dual energy absorptiometry (DXA). Data was analysed in STATA 14 using descriptive and inferential statistics. RESULTS:101 participants were recruited, with a mean age of 61±7 years. Nearly a third (n = 32) of women at baseline fulfilled global criteria for bone protection (BMD T-score ?-2SD (n = 18); BMD T-score -1.5SD to < -2SD with risk factors (n = 14). Lower body weight, body mass index (BMI), fat mass index and lean mass index were significantly associated with the participants with a BMD measurement in keeping with a diagnosis of OP (p <0.001). Low vitamin D was present in 93% of the cohort tested (n = 95), whilst deficient vitamin D status (<20ng/ml) was documented in 52 women (55%). CONCLUSIONS:In this study, a third of postmenopausal women considered for AI therapy fulfilled international criteria for bone protective pharmacological intervention. This emphasizes the need for clinical risk and BMD assessment in postmenopausal breast cancer patients at baseline. Body composition and bone health associations highlight bone fragility associated with lower body weight.

SUBMITTER: Baatjes KJ

PROVIDER: S-EPMC6445512 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Baseline bone health status in multi-ethnic South African postmenopausal breast cancer patients at initiation of aromatase inhibitor therapy: A descriptive study.

Baatjes Karin J KJ Kotze Maritha J MJ McCaul Micheal M Conradie Magda M

PloS one 20190402 4

<h4>Introduction</h4>Osteoporosis (OP) risk factor assessment and bone mineral density (BMD) testing are frequently omitted at baseline in aromatase inhibitor (AI) studies, which may lead to misinterpretation of AI associated bone loss. The present study describes bone health of South African postmenopausal women of predominantly Mixed Ancestry, prior to AI treatment.<h4>Methods</h4>This descriptive baseline study, nested in a prospective AI cohort study, included postmenopausal women with endoc ...[more]

PMID: 30939140

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Project description:Purpose:Phosphorylated ribosomal S6 kinase 1 (pS6K1) is a major downstream regulator of the mammalian target of rapamycin (mTOR) pathway. Recent studies have addressed the role of S6K1 in adipogenesis. pS6K1 may affect the outcome of estrogen depletion therapy in patients with hormone-sensitive breast cancer due to its association with adipogenesis and increased local estrogen levels. This study aimed to investigate the potential of pS6K1 as a predictive marker of adjuvant aromatase inhibitor (AI) therapy outcome in postmenopausal or ovarian function-suppressed patients with hormone-sensitive breast cancer. Methods:Medical records were retrospectively reviewed in postmenopausal or ovarian function-suppressed patients with estrogen receptor-positive and node-positive primary breast cancer. pS6K1 expression status was scored on a scale from 0 (negative) to 3+ (positive) based on immunohistochemical analysis. Results:A total of 428 patients were eligible. The median follow-up duration was 44 months (range, 1-90). In patients with positive pS6K1 expression, AIs significantly improved disease-free survival (DFS) compared to selective estrogen receptor modulators (SERMs) (5 year-DFS: 83.5% vs. 50.7%, p = 0.016). However, there was no benefit of AIs on DFS in the pS6K1 negative group (5 year-DFS 87.6% vs. 91.4%, p = 0.630). On multivariate analysis, AI therapy remained a significant predictor for DFS in the pS6K1 positive group (hazard ratio, 0.39; 95% confidence interval, 0.16-0.96; p = 0.041). pS6K1 was more effective in predicting the benefit of AI therapy in patients with ages < 50 (p = 0.021) compared to those with ages ? 50 (p = 0.188). Conclusion:pS6K1 expression may predict AI therapy outcomes and serve as a potential predictive marker for adjuvant endocrine therapy in postmenopausal and ovarian function-suppressed patients with hormone-sensitive breast cancer. AIs may be more effective in patients with pS6K1 positive tumors, while SERM could be considered an alternative option for patients with pS6K1 negative tumors.

Project description:African Swine Fever virus (ASFV) is a large double-enveloped DNA virus of the Asfarviridae family that causes a lethal hemorrhagic disease in domestic pigs and wild boars. Since 2007, a highly virulent genotype II strain has emerged and spread in Europe and South-East Asia, where millions of animals succumbed to the disease. Field- and laboratory-attenuated strains of ASFV cause highly variable clinical disease severity and survival, and mechanisms remain unclear. We hypothesized that the immunological and hygienic status of pigs is a determinant of ASF disease course. Here we compared the immunological profile at baseline and in response to ASFV infection in specific pathogen-free (SPF) and farm-raised Large White domestic pigs. At steady state, SPF pigs showed lower white blood cell counts and a lower basal inflammatory and antiviral transcriptomic profile compared to farm pigs, associated with profound differences in gut microbiome composition. After inoculation with a highly virulent ASFV genotype II strain (Armenia 2008), severe clinical signs, viremia and pro-inflammatory cytokines appeared sooner in SPF pigs, indicating a reduced capacity to control early virus replication. In contrast, during infection with an attenuated field isolate (Estonia 2014), SPF pigs presented a milder and shorter clinical disease with full recovery, whereas farm pigs presented severe protracted disease with 50% lethality. Interestingly, farm pigs showed higher production of inflammatory cytokines, whereas SPF pigs produced more anti-inflammatory IL-1ra early after infection and presented a stronger expansion of leukocytes in the recovery phase. Altogether, our data indicate that the hygiene-dependent innate immune status has a double-edge sword impact on immune responses in ASF pathogenesis. While the higher baseline innate immune activity helps the host in reducing initial virus replication, it promotes immunopathological cytokine responses, and delays lymphocyte proliferation after infection with an attenuated strain. Such effects should be considered for live vaccine development and vigilance.

Project description:Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss and poor vitamin D status in white populations, though their relative roles are not known. No previous studies have examined longitudinal changes in areal bone mineral density (aBMD), measured by dual-energy X-ray absorptiometry (DXA), or in vitamin D status in HIV-positive African women. Of 247 premenopausal, urban, black African women from Soweto, South Africa, initially recruited, 187 underwent anthropometry, DXA scanning and blood and urine collections at both baseline and 12 months. Of these, 67 were HIV-negative throughout (Nref), 60 were HIV-positive with preserved CD4 counts at baseline (Ppres), and 60 were HIV-positive with low CD4 counts at baseline, eligible for ART by South African standards of care at the time (Plow). No participant had been exposed to ART at baseline. By 12 months, 51 Plow women had initiated ART, >85% of whom took combined tenofovir disoproxil fumarate (TDF), lamivudine, and efavirenz. By 12 months, Plow and Nref, but not Ppres, increased in body weight and fat mass (group-by-timepoint p???0.001, p?=?0.002, respectively). Plow had significant decreases in aBMD of 2% to 3%, before and after size adjustment, at the femoral neck (p???0.002) and lumbar spine (p???0.001), despite significant weight gain. These decreases were associated with increased bone turnover but there were no significant differences or changes over time in vitamin D status, serum phosphate concentrations, or renal phosphate handling. Excluding data from nine Plow women unexposed to ART and 11 Ppres women who had initiated ART accentuated these findings, suggesting the bone loss in Plow was related to ART exposure. This is the first study describing DXA-defined bone loss in HIV-positive Sub-Saharan African women in association with ART. Further work is required to establish if bone loss continues with ongoing ART and, if so, whether this results in increased fracture rates. © 2017 American Society for Bone and Mineral Research.

Project description:UnlabelledThis is the first report examining vitamin D status and bone mass in African women with HIV infection using dual-energy X-ray absorptiometry (DXA) with an appropriate HIV-negative control group. Unlike previous publications, it demonstrates no difference in bone mineral density (BMD) or vitamin D status in HIV-positive patients, at different disease stages, vs. HIV-negative subjects.IntroductionLow bone mass and poor vitamin D status have been reported among HIV-positive patients; suggesting HIV or its treatment may increase the risk of osteoporosis, a particular concern for women in countries with high HIV prevalence such as South Africa. We describe bone mass and vitamin D status in urban premenopausal South African women, who were HIV positive but not on antiretroviral therapy (ARV).MethodsThis study is a cross-sectional measurement of BMD and body composition by DXA and vitamin D status by serum 25-hydroxyvitamin D (25(OH)D) concentration. Subjects were recruited into three groups: HIV negative (n = 98) and HIV positive with preserved CD₄ cell count (non-ARV; n = 74) or low CD₄ cell counts prior to ARV initiation (pre-ARV; n = 75).ResultsThe mean (standard deviation (SD)) age of women was 32.1 (7.2) years. Mean CD₄ (SD) counts (×10(6)/l) were 412 (91) and 161 (69) in non-ARV and pre-ARV groups (p < 0.0001). Pre-ARV women were significantly lighter and had lower mean BMI than the other two groups (p < 0.002). The pre-ARV group also had significantly less fat and lean mass compared with non-ARV and HIV-negative subjects (p ≤ 0.05). After full adjustment, there were no significant differences in BMD at any site (p > 0.05) between the groups, nor was vitamin D status significantly different between groups (p > 0.05); the mean (SD) cohort 25(OH)D being 60 (18) nmol/l.ConclusionContrary to previous studies, these HIV-positive women did not have lower BMD or 25(OH)D concentrations than HIV-negative controls, despite the pre-ARV group being lighter with lower BMI.

Dataset Information

Baseline bone health status in multi-ethnic South African postmenopausal breast cancer patients at initiation of aromatase inhibitor therapy: A descriptive study.

Publications

Baseline bone health status in multi-ethnic South African postmenopausal breast cancer patients at initiation of aromatase inhibitor therapy: A descriptive study.

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