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Breast Cancer Research and Treatment Jul 2024Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum...
PURPOSE
Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum oestrogen levels as a surrogate marker of safety, but methods vary. We sought to summarise the data on serum oestrogen measurement in women with breast cancer using vaginal oestrogens to better understand the methods, levels and reliability.
METHODS
We searched Medline, Embase, CENTRAL, SCOPUS and CINAHL from inception to October 2023 for clinical studies where serum oestrogen was measured in women with a history of early breast cancer using vaginal oestrogens. Studies with a reported testing methodology were included.
RESULTS
Nine studies met the inclusion criteria for this systematic review. Methods used to measure oestradiol and oestriol in selected studies included mass spectrometry and immunoassays; several studies used more than one with variable concordance. Mass spectrometry detected oestradiol levels down to a lower limit between 1.0 pg/mL and 3.0 pg/mL. Immunoassays such as ELISA (enzyme-linked immunosorbent assay), ECLIA (enhanced chemiluminiscence immunoassay) and RIA (radioimmunoassay) had lower detection limits ranging between 0.8 pg/mL and 10 pg/mL. Studies were heterogeneous in testing techniques used, timing of testing, and the population including with subsequent varying results in the effect on oestrogens reported.
CONCLUSIONS
Adopting consistent and standardised methods of measuring oestrogens in clinical trials involving women with early breast cancer on vaginal oestrogens is critical. Serum oestrogens are used as a surrogate marker of safety in this population, and good-quality data are necessary to enable clinicians and patients to feel confident in prescribing and taking vaginal oestrogens. Mass spectrometry, although more expensive, gives more reliable results when dealing with very low levels of oestrogens often found in women on aromatase inhibitors, compared to immunoassays.
Topics: Female; Humans; Administration, Intravaginal; Breast Neoplasms; Cancer Survivors; Estradiol; Estriol; Estrogens; Vagina
PubMed: 38780887
DOI: 10.1007/s10549-024-07364-0 -
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 -
Frontiers in Endocrinology 2024The role of simultaneous neoadjuvant endocrine therapy in chemotherapy in HR+HER2- breast cancer continues to be controversial. This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The role of simultaneous neoadjuvant endocrine therapy in chemotherapy in HR+HER2- breast cancer continues to be controversial. This systematic review and meta-analysis was conducted to further evaluate the effectiveness and safety of this strategy for HR+HER2- breast cancer patients. Trials in which HR+HER2- breast cancer patients were randomly assigned to either single or simultaneous endocrine-assisted neoadjuvant chemotherapy were eligible for inclusion. The prime endpoint was the pathological complete response (pCR) rate. The clinical response (complete clinical response: CR, partial response: PR) and safety were secondary endpoints. A random effect model was used for statistical analysis. A total of 690 patients from five trials were included. PCR rate was 10.43% in the concomitant endocrine group and 7.83% in control group (OR=1.37, 95%CI 0.72-2.60, P=0.34). The CR rate was 15.50% for the concomitant endocrine group and 10.26% for the control group. (OR=1.61, 95%CI 0.99-2.61, P=0.05). ORR (CR+PR) was significantly higher in the simultaneous endocrine group compared to the control group (79.53% (272/342) vs. 70.09% (239/341) , OR=1.70, 95%CI 1.19-2.43, P=0.004) and the meta-analysis approach showed no heterogeneity (I 0%, P=0.54) . Tamoxifen concurrent with chemotherapy could increase the frequency of adverse events, whereas aromatase inhibitors (AIs) would not. Our findings provide evidence for the efficacy and safety of concurrent neoadjuvant endocrine therapy (AIs) with chemotherapy as an available option to achieve a higher clinical response rate for HR+HER2- breast cancer patients compared with chemotherapy alone with low toxicity.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022340725.
Topics: Humans; Female; Breast Neoplasms; Neoadjuvant Therapy; Tamoxifen; Combined Modality Therapy; Aromatase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 38481446
DOI: 10.3389/fendo.2024.1254213 -
Bulletin Du Cancer Apr 2024Evaluating the benefits and risks of prolonged hormonal treatment with aromatase inhibitors (AIs) for treating hormone-dependent breast cancer. (Meta-Analysis)
Meta-Analysis
[Effects of extended aromatase inhibitors in women with hormone-dependent breast cancer who have already received five years of adjuvant hormone therapy: A systematic review and meta-analysis].
INTRODUCTION
Evaluating the benefits and risks of prolonged hormonal treatment with aromatase inhibitors (AIs) for treating hormone-dependent breast cancer.
METHODS
A systematic review and meta-analysis was conducted. Studies reporting on randomized clinical trials concerning prolongating hormonal therapy with AIs as compared to a placebo or no prolongation, after an initial five years of hormonal therapy, were eligible.
RESULTS
Seven clinical trials were included. Prolonged AI therapy was associated with a statistically significant improvement in disease-free survival (RR=0.70, 95% CI 0.60 to 0.80). A statistically significant increase was observed for osteoporosis (RR=1.17, 95% CI 1.03 to 1.33), hot flushes/flashes (RR=1.27, 95% CI 1.08 to 1.49), myalgia (RR=1.23, 95% CI 1.09 to 1.39), fractures (RR=1.26, 95% CI 1.09 to 1.45) and arthralgia (RR=1.17, 95% CI 1.10 to 1.25). However, no statistically significant association was observed between prolonged AI therapy and overall survival, cardiovascular events, and bone pain.
DISCUSSION
Prolonged AI therapy has significant benefits in terms of disease-free survival in women with hormone-dependent breast cancer. However, adverse effects and a lack of evidence for a benefit on overall survival must be considered in the decision-making process regarding adjuvant hormone therapy extension.
Topics: Female; Humans; Breast Neoplasms; Aromatase Inhibitors; Combined Modality Therapy; Chemotherapy, Adjuvant; Adjuvants, Immunologic; Hormones; Antineoplastic Agents, Hormonal; Tamoxifen
PubMed: 38453587
DOI: 10.1016/j.bulcan.2023.12.016 -
Future Oncology (London, England) Feb 2024Perivascular epithelioid cell neoplasms (PEComas) are rare mesenchymal lesions, with gynecological PEComas accounting for just over a quarter of cases. Limited reports...
Perivascular epithelioid cell neoplasms (PEComas) are rare mesenchymal lesions, with gynecological PEComas accounting for just over a quarter of cases. Limited reports exist on gynecological PEComa, primarily treated with surgery; adjuvant therapy is considered in high-risk cases. This systematic review aims to summarize the origin and clinical, pathological and molecular characteristics of uterine PEComa, focusing on treatment options for gynecological PEComa. A comprehensive PubMed review of gynecological PEComa reports was conducted. A detailed examination of the literature ensured a thorough understanding. Gynecological PEComa diagnosis relies on histology and immunology. Despite therapy controversies, surgery remains the mainstay. Adjuvant therapy efficacy in high-risk cases is uncertain. mTOR inhibitors are the first line; alternative treatments, including angiogenesis and aromatase inhibitors, should be considered.
Topics: Female; Humans; Combined Modality Therapy; Diagnosis, Differential; Gynecology; Perivascular Epithelioid Cell Neoplasms
PubMed: 38426361
DOI: 10.2217/fon-2023-0778 -
Supportive Care in Cancer : Official... Feb 2024To evaluate the effect of telehealth interventions on adherence to endocrine therapy among patients with breast cancer. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the effect of telehealth interventions on adherence to endocrine therapy among patients with breast cancer.
METHODS
A systematic search of five English databases (PubMed, Web of Science, Embase, the American Psychological Association PsycNet, and the Cochrane Library) and four Chinese databases (Chinese National Knowledge Infrastructure, SinoMed, WanFang Data, and WeiPu Data) was performed from inception to March 31, 2023. Two investigators independently screened the available studies for eligibility and extracted relevant data. Quality assessment was conducted using the Cochrane Risk of Bias Tool. The effect size was computed based on the risk ratio for dichotomous data and standardized mean difference for continuous data using Review Manager 5.4.
RESULTS
A total of 1,780 participants from eight randomized controlled trials were included. These studies involved treatment with aromatase inhibitors only (n = 3) or aromatase inhibitors plus tamoxifen (n = 5). Telehealth interventions involved web-based interventions, telephone-based interventions, interventions via mobile applications, and interventions based on technology. In three studies, subjective measures were used, while objective measures were utilized in another three. Two studies incorporated a combination of both subjective and objective measures. The duration of the interventions varied among studies, ranging from a week to 36 months. The follow-up duration ranged from 4 weeks to 36 months. The quality of included studies was moderate to high. The meta-analysis of the five studies reporting dichotomous data showed that telehealth interventions had a significant effect on adherence to endocrine therapy (RR = 0.86, 95% CI = 0.76-0.97). Moreover, four studies reported continuous data. The meta-analysis demonstrated that telehealth interventions significantly improved adherence to endocrine therapy at 1 month (SMD = 0.50, 95% CI = 0.10-0.90), 3 months (SMD = 0.58, 95% CI = 0.17-0.99), and 6 months (SMD = 0.27, 95% CI = 0.08-0.47) of follow-up.
CONCLUSION
Telehealth interventions may facilitate adherence to endocrine therapy among patients with breast cancer. Further research should adopt a theory-based design and explore the longer-term effects.
Topics: Humans; Female; Breast Neoplasms; Aromatase Inhibitors; Telemedicine
PubMed: 38332357
DOI: 10.1007/s00520-024-08339-z -
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 -
Obstetrics and Gynecology Jan 2024To estimate the effect of medical management on the size of ovarian endometriomas. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the effect of medical management on the size of ovarian endometriomas.
DATA SOURCE
Online databases were searched from inception to October 2022, including Ovid MEDLINE, Ovid EMBASE, PubMed, EBM Reviews-Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov , and Web of Science.
METHODS OF STUDY SELECTION
Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we included all English-language, full-text articles that reported on change in endometrioma size (either diameter or volume) after medical interventions. Studies evaluating surgical interventions or postoperative recurrence were excluded. All screening and data extraction were performed independently by two authors. Risk of bias assessment was performed with either the Cochrane Risk of Bias Tool for randomized controlled trials or a modified Newcastle-Ottawa Scale for observational studies.
TABULATION, INTEGRATION, AND RESULTS
After removal of duplicates, 9,332 studies were screened, with 33 full-text articles deemed eligible for inclusion. In the meta-analysis, dienogest showed significant reduction in cyst diameter (reduction 1.32 cm, 95% CI, 0.91-1.73, eight studies, n=418 cysts) and volume (mean difference of log-transformed volume 1.35, 95% CI, 0.87-1.83, seven studies, n=282 cysts). Similarly, significant reductions were seen with the oral contraceptive pill (OCP) (1.06 cm, 95% CI, 0.59-1.53, nine studies, n=455), gonadotropin-releasing hormone (GnRH) agonists (1.17 cm, 95% CI, 0.42-1.92, four studies, n=128 cysts), norethindrone acetate (0.6 cm, 95% CI, 0.27-0.94, two studies, n=88 cysts), and danazol (1.95 cm, 95% CI, 1.18-2.73, two studies, n=34 cysts). Norethindrone acetate with aromatase inhibitor was also effective in reducing endometrioma volume (mean difference of log-transformed volume 1.47, 95% CI, 0.16-2.78, two studies, n=34 cysts).
CONCLUSION
Medical management with dienogest, OCPs, GnRH agonists, norethindrone acetate, norethindrone acetate with aromatase inhibitor, or danazol can reduce the size of ovarian endometriomas.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD 42022363319.
Topics: Female; Humans; Endometriosis; Danazol; Norethindrone Acetate; Aromatase Inhibitors; Gonadotropin-Releasing Hormone; Cysts
PubMed: 37944155
DOI: 10.1097/AOG.0000000000005444 -
European Journal of Cancer (Oxford,... Nov 2023Neoadjuvant treatment discriminates responders, but pathologic complete response is uncommon in oestrogen receptor (ER)-positive/HER2-negative early breast cancer. We... (Meta-Analysis)
Meta-Analysis
Ki-67 index after neoadjuvant endocrine therapy as a prognostic biomarker in patients with ER-positive/HER2-negative early breast cancer: a systematic review and meta-analysis.
BACKGROUND
Neoadjuvant treatment discriminates responders, but pathologic complete response is uncommon in oestrogen receptor (ER)-positive/HER2-negative early breast cancer. We aimed to assess the prognostic value of Ki-67 index after neoadjuvant endocrine therapy (NET).
METHODS
We conducted a systematic literature search of PubMed, Embase, CENTRAL, and conference proceedings up to 22nd August 2023 to identify studies reporting the association of Ki-67 index after NET with recurrence-free survival (RFS) and/or overall survival (OS) in women with ER-positive/HER2-negative early breast cancer. We combined RFS and OS hazard ratios (HRs) with 95% confidence intervals (CIs).
RESULTS
Twelve studies including 7897 patients were analysed. Most studies were clinical trials (n = 7547) including only postmenopausal women (n = 3953) treated with aromatase inhibitor (n = 3359). Three studies evaluated Ki-67 in a preplanned core biopsy at 2-4 weeks of NET (n = 3348), while nine evaluated Ki-67 in the surgical specimen (n = 4549) after 2-24 weeks of NET. Median follow-up ranged between 37 and 95 months for RFS and 62-84 months for OS. High Ki-67 index after NET was significantly associated with worse RFS (HR 2.48, 95% CI 1.86-3.30) and OS (HR 2.66, 95% CI 1.65-4.28). A sensitivity analysis including three studies that measured Ki-67 in a preplanned core biopsy showed similar association with RFS (HR 2.41, 95% CI 1.77-3.30).
CONCLUSIONS
High Ki-67 after NET is associated with worse survival outcomes, even after a short course of NET, emphasising the prognostic value of this biomarker in women with ER-positive/HER2-negative early breast cancer.
Topics: Humans; Female; Breast Neoplasms; Neoadjuvant Therapy; Ki-67 Antigen; Prognosis; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37857118
DOI: 10.1016/j.ejca.2023.113358 -
Transgender Health Oct 2023Testosterone therapy prompts the development of male secondary sexual characteristics coupled with numerous physiological changes; however, the effect of prolonged... (Review)
Review
Preservation of Fertility in Transgender Men on Long-Term Testosterone Therapy: A Systematic Review of Oocyte Retrieval Outcomes During and After Exogenous Androgen Exposure.
Testosterone therapy prompts the development of male secondary sexual characteristics coupled with numerous physiological changes; however, the effect of prolonged androgen exposure on transgender men's fertility remains to be fully elucidated. Multiple clinical consensuses advise assisted reproduction before hormone treatment and state that fertility preservation following androgen therapy entails the suspension of testosterone administration. Although the desire for reproduction among transgender men is prevalent, the discontinuation of gender-affirming hormone therapy poses a major challenge due to the anxiety, unease, and gender dysphoria that follow androgen withdrawal. The present investigation aimed to explore the feasibility and outcomes of oocyte retrieval in adult transgender men undergoing testosterone administration before or during fertility preservation. Seven case reports, four cohort studies, and two cross-sectional studies were identified following a systematic literature search on the PubMed/Ovid MEDLINE, Scopus, and ScienceDirect databases. The findings gathered in this review disclose the viability of oocyte retrieval after prolonged androgen exposure and suggest the absence of a direct relationship between the duration of testosterone suspension and fertility preservation outcomes. Although the reports are limited, recent evidence shows that continuous testosterone administration and the use of aromatase inhibitors during ovarian stimulation could potentially reduce the distressing effects of hormonal ovulation induction. New approaches to fertility preservation in transgender men must be further explored to ensure interventions aligned both with the reproductive desire and avoidance of gender dysphoria exacerbation that follow hormone therapy suspension.
PubMed: 37810944
DOI: 10.1089/trgh.2022.0023