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Journal of Clinical Medicine Mar 2024Women are typically diagnosed with estrogen receptor-positive breast cancer around the postmenopausal period when declining estrogen levels initiate changes in lipid... (Review)
Review
Women are typically diagnosed with estrogen receptor-positive breast cancer around the postmenopausal period when declining estrogen levels initiate changes in lipid profiles. Aromatase inhibitors (AI) are used to prevent the progression of cancer; however, a further reduction in estrogen levels may have detrimental effects on lipid levels, which was our working hypothesis. Our meta-analysis was conducted on the lipid profiles of postmenopausal breast cancer patients at baseline and at different treatment time points. We identified 15 studies, including 1708 patients. Studies using anastrozole (ANA), exemestane (EXE), letrozole (LET), and tamoxifen (TMX) were involved. Subgroup analyses revealed that 3- and 12-month administrations of LET and EXE lead to negative changes in lipid profiles that tend to alter the lipid profile undesirably, unlike ANA and TMX. Our results suggest that, despite statistically significant results, EXE and LET may not be sufficient to cause severe dyslipidemia in patients without cardiovascular comorbidities according to the AHA/ACC Guideline on the Management of Blood Cholesterol. However, the results may raise the question of monitoring the effects of AIs in patients, especially those with pre-existing cardiovascular risk factors such as dyslipidemia.
PubMed: 38542042
DOI: 10.3390/jcm13061818 -
American Journal of Cardiovascular... Jan 2024Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients' symptoms and reversing pulmonary vascular pathology.
METHOD
We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CDR42022340658) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Overall, 5092 records were screened from different database and registries; 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. However, the main findings of this SR relate to the powerful potential of the AMPK activator and the imminent antidiabetic drug metformin, and the BMP2 inhibitor sotatercept as promising PAH-modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor fasudil and the estrogen aromatase inhibitor anastrozole in PAH patients. The role of tacrolimus in PAH is questionable. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging.
CONCLUSION
Metformin and sotatercept appear as promising therapeutic drugs for PAH.
CLINICAL TRIALS REGISTRATION
This work was registered in PROSPERO (CDR42022340658).
Topics: Humans; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; AMP-Activated Protein Kinases; Familial Primary Pulmonary Hypertension; Estrogens; Metformin
PubMed: 37945977
DOI: 10.1007/s40256-023-00613-5 -
Journal of Oncology Pharmacy Practice :... Jun 2023To map the evidence available in the literature on the health-related quality of life of women with breast cancer using hormone therapy. (Review)
Review
OBJECTIVE
To map the evidence available in the literature on the health-related quality of life of women with breast cancer using hormone therapy.
DATA SOURCES
This review followed the Joanna Briggs Institute methodological recommendations and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews reporting guidelines. Searches were performed in nine databases using descriptors, synonyms and keywords; grey literature was also included. The review protocol was registered with the Open Science Framework under doi: http://doi.org/10.17605/OSF.IO/347FM. Inclusion criteria were established according to the Population, Concept, and Context strategy. The selection of studies was performed by two independent reviewers with the aid of RAYYAN software and disagreements were resolved by a third reviewer. The main information from the included articles was grouped into textual categories and presented by means of a narrative synthesis.
DATA SUMMARY
A total of 5419 records were identified, of which 42 studies fully met the eligibility criteria. Most were multicenter studies (42.9%) and randomized controlled trials (62%). Most studies addressed anastrozole (39.5%), letrozole (34.2%), and tamoxifen (26.3%), which were studied alone or in combination. The most widely used health-related quality-of-life assessment tool was the EORTC-QLQ-C30. The concomitant use of hormone therapy and cyclin-dependent kinase inhibitors 4 and 6 showed improvement in health-related quality of life.
CONCLUSION
In recent years there has been an increase in studies focused on health-related quality of life, and the evidence pointed to relevant information on health-related quality of life and the use of endocrine therapy, tamoxifen in combination with aromatase inhibitors, as well as aromatase inhibitor alone and the use of cyclin-dependent kinase 4 and 6.
Topics: Female; Humans; Breast Neoplasms; Quality of Life; Anastrozole; Tamoxifen; Aromatase Inhibitors; Hormones
PubMed: 37021486
DOI: 10.1177/10781552231168071 -
Clinical Therapeutics Sep 2022We aimed to investigate the impact of anastrozole administration on the traditional components of the lipid profile (ie, total cholesterol [TC], LDL-C, HDL-C, and... (Meta-Analysis)
Meta-Analysis
PURPOSE
We aimed to investigate the impact of anastrozole administration on the traditional components of the lipid profile (ie, total cholesterol [TC], LDL-C, HDL-C, and triglycerides [TGs]) by means of a systematic review and meta-analysis of randomized controlled trials.
METHODS
We searched the PubMed/Medline, Scopus, Embase, and Web of Science databases for relevant randomized controlled trials published in the English language until January 18, 2022. The weighted mean difference (WMD) and 95% CIs were calculated using a random-effects model (DerSimonian and Laird methods).
FINDINGS
Anastrozole administration significantly lowered TC concentrations when the treatment duration was ≤3 months (WMD = -2.73 mg/dL; 95% CI, -5.09 to -0.38 mg/dL; P = 0.02) and when the baseline TC concentration was ≥200 mg/dL (WMD = -3.64 mg/dL; 95% CI, -6.30 to -0.98 mg/dL; P = 0.007). HDL-C levels decreased after anastrozole administration when the treatment duration was >3 months (WMD = -1.67 mg/dL; 95% CI, -3.24 to -0.10 mg/dL; P = 0.03). Anastrozole administration had no impact on TG or LDL-C values.
IMPLICATIONS
Anastrozole administration in humans can decrease TC and HDL-C levels but has no effect on LDL-C or TG concentrations.
Topics: Anastrozole; Cholesterol, LDL; Humans; Lipids; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 36031476
DOI: 10.1016/j.clinthera.2022.08.003 -
Frontiers in Pharmacology 2022To identify the optimal initial 5 years of adjuvant endocrine therapy for hormone receptor-positive postmenopausal early breast cancer (EBC) patients. We conducted a...
Efficacy and Safety of Initial 5 Years of Adjuvant Endocrine Therapy in Postmenopausal Hormone Receptor-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis.
To identify the optimal initial 5 years of adjuvant endocrine therapy for hormone receptor-positive postmenopausal early breast cancer (EBC) patients. We conducted a systematic search of the PubMed, Web of Science, and EMBASE to obtain relevant studies published between January 2000 and January 2022. Randomized clinical trials assessing the efficacy and safety of initial 5 years of adjuvant endocrine therapy were included. The primary outcomes were disease-free survival and overall survival and the secondary outcome was severe adverse effects (SAEs). A Bayesian network meta-analysis was carried out to indirectly compare all regimens and the value of surface under the cumulative ranking curve (SUCRA) was used to obtain rankings. Eleven studies with 49,987 subjects were included. For DFS, exemestane (EXE) [hazard ratio (HR) 0.91, 95% confidence interval (95%CI) 0.87-0.96], anastrozole (ANA) (0.94, 0.90-0.97), letrozole (LET) (0.93, 0.89-0.97), tamoxifen (TAM) followed by EXE (0.91, 0.87-0.96), and TAM followed by ANA (0.92, 0.87-0.98) were more favorable than TAM, with TAM followed by EXE ranking as the first of SUCRA. For OS, only TAM followed by ANA showed significant superiority than TAM (HR 0.91, 95%CI 0.86-0.97) and ranked as the first of SUCRA. For SAEs, EXE (HR 1.72, 95%CI 1.04-2.98), ANA (1.58, 1.03-2.43), and LET (1.63, 1.02-2.57) showed greater associations with bone fracture than TAM. However, no significant difference in the incidences of cardiac events, thromboembolic events, and cerebrovascular events was found among all comparisons. The sequential use of aromatase inhibitors, which has the best curative effects and relatively mild side effects, may be the optimal treatment mode for hormone receptor-positive postmenopausal EBC patients. In addition, the three kinds of aromatase inhibitors achieved roughly equal efficacy, but caused different types of SAEs. [website], identifier [registration number].
PubMed: 35721183
DOI: 10.3389/fphar.2022.886954 -
Andrology Jul 2022Aromatase inhibitors (AIs) have been used to treat male infertility for decades. However, due to the lack of large-scale randomized controlled studies and basic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aromatase inhibitors (AIs) have been used to treat male infertility for decades. However, due to the lack of large-scale randomized controlled studies and basic research, the efficacy and safety of AIs in the treatment of male infertility remain controversial. Therefore, it is necessary to conduct an evidence-based preliminary evaluation of the existing clinical trials of AIs in the treatment of male infertility.
METHOD
A comprehensive literature search was performed in the PubMed, Embase, Cochrane, CNKI, VIP, CBM, and Wanfang databases through August 2021 for all studies. We conducted a systematic review with a meta-analysis of all available studies reporting sperm conventional parameters, gonadotropin and testosterone levels, and/or the pregnancy rate.
RESULTS
A total of 10 studies involving 666 patients were included. Letrozole (LE) or anastrozole (AZ) administration significantly increased sperm concentration, total sperm count, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) levels, and the testosterone-to-estradiol ratio (T/E2), but E2 levels were significantly reduced compared with baseline values. Compared with the control group, which included selective estrogen receptor modulators (SEMRs) or human chorionic gonadotropin (HCG), LE, or AZ did not have any significant effect on sperm concentration, motility, and morphology, except that AIs had less effect on sperm motility than the control group (weighted mean difference [WMD]: -2.55; 95% CI: -4.11 to -1.00; p = 0.001).
CONCLUSION
AIs may be effective in the treatment of male infertility. For infertile male patients planning assisted reproduction, discontinuation of AIs for 2-7 days prior to sperm retrieval may increase the success rate of fertilization. Further studies with larger sample sizes are needed to validate these findings.
Topics: Anastrozole; Estradiol; Female; Follicle Stimulating Hormone; Humans; Infertility, Male; Letrozole; Male; Pregnancy; Semen; Sperm Motility; Testosterone
PubMed: 35438843
DOI: 10.1111/andr.13185 -
Pain Management Nursing : Official... Aug 2022Despite the widespread use of complementary and alternative medicine by patients and physicians alike, there is no accurate evidence regarding the effects of vitamin D... (Review)
Review
OBJECTIVES
Despite the widespread use of complementary and alternative medicine by patients and physicians alike, there is no accurate evidence regarding the effects of vitamin D supplementation on treatment-induced pain in cancer patients. Thus, the aim of this systematic review of randomized controlled trials (RCTs) was to evaluate the impact of vitamin D administration on therapy-related pain in subjects diagnosed with malignant disorders.
REVIEW ANALYSIS METHODS
We searched the Web of Science, Scopus, PubMed/Medline, Embase, and Google Scholar databases up to October 2020 to identify published RCTs that investigated the use of vitamin D in the management of treatment-induced pain in individuals with cancer.
RESULTS
Nine RCTs were detected. The median duration of the intervention was of 24 weeks (range 12-52 weeks) and dose of vitamin D employed was 2000-50000 IU of vitamin D3 weekly orally each day. Six RCTs reported a significant reduction in pain, whereas three did not detect a notable decrease of this variable. Of the six studies that reported an alleviation of pain, an RCT which recruited 60 participants and lasted for 24 weeks consisted of supplementation with high doses of vitamin D2 weekly for 8 weeks in women receiving anastrozole as adjuvant therapy, then supplementation with vitamin D2 monthly for 4 months, effectively alleviated the aromatase inhibitor-associated musculoskeletal syndrome (AIMSS). The results of the same RCT also suggested a beneficial effect of vitamin D on musculoskeletal pain.
CONCLUSIONS
Our results suggest that the supplementation with high doses of vitamin D in cancer patients with low serum levels of vitamin D, can be effective in reducing treatment-related pain.
Topics: Cancer Pain; Dietary Supplements; Ergocalciferols; Female; Humans; Musculoskeletal Pain; Neoplasms; Vitamin D
PubMed: 35279360
DOI: 10.1016/j.pmn.2022.02.001 -
Breast Cancer (Tokyo, Japan) May 2021The relationship between obesity and prognosis of early breast cancer is complex. Increased levels of aromatase present in adipose tissue of obese postmenopausal women...
BACKGROUND
The relationship between obesity and prognosis of early breast cancer is complex. Increased levels of aromatase present in adipose tissue of obese postmenopausal women may lead to suboptimal suppression of systemic estrogens. However, studies have been mixed with respect to the association between use of aromatase inhibitors (AIs) and clinical outcomes in obese women with early breast cancer.
METHODS
We conducted a systematic literature review following PRISMA guidelines to examine the impact of obesity on the efficacy of AIs in early-stage hormone receptor-positive breast cancer. Primary outcome measures included disease-free survival, relapse-free survival, distant recurrence-free survival, breast cancer-free survival, and overall survival.
RESULTS
Of 491 studies identified, eight studies met criteria for inclusion: three retrospective cohort studies, one prospective cohort study and four randomized controlled trials. Four studies limited eligibility to postmenopausal women. Percentage of obese patients in studies ranged from 10 to 30%. Two studies examined use of AIs alone while the remainder included patients treated with either AIs or tamoxifen. Five out of seven studies suggested a negative impact of obesity on AI efficacy.
CONCLUSIONS
The results of our systematic review highlight a need for further research exploring the optimal endocrine therapies for obese women. There is insufficient evidence at present to recommend tailoring adjuvant endocrine therapy with use of specific AIs or for dosing modifications of AIs in this patient population.
Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Body Mass Index; Breast Neoplasms; Disease-Free Survival; Female; Humans; Neoplasm Recurrence, Local; Obesity; Progression-Free Survival; Tamoxifen; Treatment Outcome
PubMed: 33428124
DOI: 10.1007/s12282-020-01213-w -
Annals of Plastic Surgery Oct 2020Patients with hormone receptor-positive breast tumors receive hormonal therapy with either selective estrogen receptor modulators (SERMs) (eg, tamoxifen) or aromatase...
BACKGROUND
Patients with hormone receptor-positive breast tumors receive hormonal therapy with either selective estrogen receptor modulators (SERMs) (eg, tamoxifen) or aromatase inhibitors (AIs) (eg, anastrozole) for 5 to 10 years. Patients are using these therapies frequently during breast reconstruction. Literature investigating the effects of hormonal modulators on breast reconstruction outcomes demonstrates conflicting results. We sought to perform a systematic evaluation to assess the effects of hormonal therapy on breast reconstruction outcomes and to guide perioperative management of antiestrogen therapies.
METHODS
A MEDLINE, PubMed, and EBSCO Host search of articles regarding the effects of SERMs and AIs on breast reconstruction was performed. Outcomes evaluated included wound complications, total or partial flap loss, and thromboembolic events. Included studies were assigned Methodological Index for Nonrandomized Studies quality scores.
RESULTS
A total of 2581 flaps were analyzed for complete loss: patients taking SERMs at the time of reconstruction had higher rates of flap loss compared with patients not taking hormone modulators (P < 0.001). Flap loss was not affected by concurrent AI use (P = 0.11). Both SERMs and AIs had an increased risk of donor site complications (P = 0.0021 and P < 0.0001, respectively). Neither hormone modulator had an effect on flap wound complications or venous thromboembolic event rates.
CONCLUSIONS
Evidence indicates patients using SERMs at the time of operation are at an increased risk of flap loss and those taking either SERMs or AIs have higher rates of donor site complications. These findings support holding these medications for 1 to 2 half lives (tamoxifen, 14-28 days; AIs, 2-4 days) preoperatively.
Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Estrogen Antagonists; Estrogen Receptor Modulators; Humans; Mammaplasty; Tamoxifen
PubMed: 32332390
DOI: 10.1097/SAP.0000000000002394 -
Breast Cancer (Tokyo, Japan) May 2020In establishing the 2018 Breast Cancer Practice Guidelines of the Japan Breast Cancer Society, we explored the optimal first-line endocrine therapy for advanced... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In establishing the 2018 Breast Cancer Practice Guidelines of the Japan Breast Cancer Society, we explored the optimal first-line endocrine therapy for advanced postmenopausal hormone receptor-positive breast cancer.
METHODS
We performed a systematic review of relevant reports from randomized-controlled studies published prior to November 2016 found using medical journal search engines. The main outcomes which we evaluated were progression-free survival (PFS), objective response rate (ORR), disease control rate (CBR), and toxicity.
RESULTS
Four controlled trials comparing aromatase inhibitors (AI) and cyclin-dependent kinase (CDK)4/6 inhibitor combination therapy to AI monotherapy, and two controlled trials comparing anastrozole to fulvestrant 500 mg were analyzed. AI/CDK4/6 inhibitor combination therapy significantly improved PFS (Risk Ratio: 0.67, 95%CI 0.60-0.73), increased ORR (Risk Difference: 0.11, 95% CI 0.07-0.16), and increased CBR (Risk Difference: 0.11, 95% CI 0.07-0.15), compared with AI monotherapy. Patients who received this combination therapy had a higher grade ≥ 3 adverse event rate more than those who received AI monotherapy (Risk Difference: 43%, 95%CI: 0.39-0.47). Fulvestrant 500 mg alone significantly improved PFS (risk ratio: 0.85, 95%CI 0.72-0.98), but ORR and CBR were similar to those of anastrozole alone.
CONCLUSION
In the first-line treatment for advanced postmenopausal hormone receptor-positive breast cancer, a combination therapy of CDK4/6 inhibitors and AI showed significant improvement of PFS, ORR, and CBR but with significant increased toxicities compared with AI alone. Fulvestrant 500 mg monotherapy significantly prolonged PFS compared with AI monotherapy. We must wait for the results of the studies with longer follow-up period.
Topics: Aromatase Inhibitors; Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Postmenopause; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone
PubMed: 32043218
DOI: 10.1007/s12282-020-01054-7