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European Journal of Cancer (Oxford,... Nov 2023Adjuvant hormonal therapy, with or without prior chemotherapy, has been widely recognised as the preferred treatment strategy for resected breast cancer (BC) for a... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Adjuvant hormonal therapy, with or without prior chemotherapy, has been widely recognised as the preferred treatment strategy for resected breast cancer (BC) for a minimum duration of 5 years. If the effectiveness of therapy beyond a 5-year period has been established, there is still ongoing debate regarding the optimal duration for this prolonged period. A network meta-analysis (NMA) was conducted to ascertain the optimal duration of extended therapy for resected BC in postmenopausal women.
MATERIAL AND METHODS
A comprehensive search was conducted on online databases, including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, to identify all randomised trials on extended duration of endocrine therapy. The search was limited to trials that had been published before 30th April 2023. The study focused on evaluating disease-free survival (DFS) as the primary outcome, with overall survival (OS) as the secondary endpoint. Under the Bayesian framework, NMA was performed using the GeMTC package. The relative rankings of the treatments were determined by utilising surface under the cumulative ranking curve (SUCRA) p scores. A network meta-regression analysis was employed to ascertain the impact of the baseline characteristics of the disease and the initial treatments administered.
RESULTS
In the overall population, increasing the duration by 5 years did not result in a significantly better DFS compared to durations of 2-3 and 3-4 more years (hazard ratio [HR] = 0.97, 95% confidence interval [CI] [0.88-1.08] and HR = 0.87, 95% CI [0.72-1.06]). This effect was independent of adjuvant chemotherapy and nodal status. However, the effect of 5 more years of AI was significantly better in node-positive BC and in those who received some years of tamoxifen instead of aromatase inhibitors (AIs) as initial adjuvant therapy. OS was not affected by the administration of extended endocrine therapy.
CONCLUSIONS
We conclude that an extended course of AI lasting 2-3 years, following an initial 5-year treatment, may be considered an appropriate regimen for achieving DFS benefits. In node-positive BC cases, it has been observed that a duration of 10 years provides a greater advantage compared to shorter durations, especially when tamoxifen is administered initially. Therefore, it is suggested that a longer duration is a potential standard of care in these cases.
Topics: Humans; Female; Breast Neoplasms; Antineoplastic Agents, Hormonal; Postmenopause; Bayes Theorem; Network Meta-Analysis; Tamoxifen; Aromatase Inhibitors; Chemotherapy, Adjuvant; Adjuvants, Immunologic
PubMed: 37769477
DOI: 10.1016/j.ejca.2023.113322 -
Annales D'endocrinologie Feb 2024Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of...
BACKGROUND
Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of genetically proven 46,XX aromatase deficiency patients to evaluate hormonal parameters.
METHODS
Retrospective review of case records, collating phenotypic and genotypic data and molecular modeling. Systematic review of 46,XX aromatase deficiency, analyzing data on gonadotropins, estrogen and androgens.
RESULTS
In the seven patients from our center, presentation was frequent in childhood or adolescence (4/7: delayed puberty or hyperandrogenism), with maternal virilization (4/7), predominance of Prader III/IV (5/7), and initial rearing as females (6/7). Three patients had hypoplastic ovaries. One patient had spontaneous regular menses. We report three novel (p.Arg115Pro, p.Arg192Pro, and c.145+1_145+4delins) and two recurrent variants (p.Val370Met, and c.145+1_145+4delins) in western and northern India, respectively. On systematic review (n=43), gonadotropins were elevated (FSH>LH) across ages (except preterm infants), androgens were elevated in about one-third of cases during childhood and puberty, and estradiol was lower than in controls in mini-puberty and puberty. Spontaneous thelarche and streak ovaries were significantly more frequent in patients with non-truncating and truncating variants, respectively.
CONCLUSION
We report uncommon presentations with possible founder variants, and highlight hormonal parameters across ages. Serum FSH levels were elevated except in preterms, and can be used as a diagnostic marker.
Topics: Male; Infant; Female; Adolescent; Humans; Infant, Newborn; Infant, Premature; Gynecomastia; Androgens; Follicle Stimulating Hormone; Gonadotropins; Aromatase; Infertility, Male; Metabolism, Inborn Errors; 46, XX Disorders of Sex Development
PubMed: 37348676
DOI: 10.1016/j.ando.2023.05.010 -
Neurological Sciences : Official... Dec 2019CYP19A1 enzyme (aromatase) encoded by CYP19A1 (cytochrome p450 family 19 subfamily a member 1) gene plays a key role in the biosynthesis of estrogen, which has been... (Meta-Analysis)
Meta-Analysis
Association between rs10046, rs1143704, rs767199, rs727479, rs1065778, rs1062033, rs1008805, and rs700519 polymorphisms in aromatase (CYP19A1) gene and Alzheimer's disease risk: a systematic review and meta-analysis involving 11,051 subjects.
BACKGROUND
CYP19A1 enzyme (aromatase) encoded by CYP19A1 (cytochrome p450 family 19 subfamily a member 1) gene plays a key role in the biosynthesis of estrogen, which has been significantly associated with Alzheimer's disease (AD). To ascertain whether CYP19A1 gene polymorphisms are correlated with the susceptibility to AD, we performed this systematic review and meta-analysis of currently available studies.
MATERIALS AND METHODS
A comprehensive literature search was conducted by using PubMed, Embase, and Web of Science databases and the Cochrane Library. The association was evaluated by using odds ratios (ORs) and 95% confidence intervals (CIs) through Stata software (version 12.0).
RESULTS
A total of eight articles including 39 case-control studies with 11,051 subjects including 3215 AD cases and 7836 controls were involved in this meta-analysis. By pooling all eligible studies, we detected that rs10046, rs1143704, rs767199, and rs727479 polymorphisms in CYP19A1 gene were significantly associated with AD risk. A significant association between rs10046 polymorphism and AD risk was found under allele contrast, homozygous (TT vs CC: OR = 1.17, 95%CI = 1.02-1.34, I = 0.0%, P = 0.026), and dominant genetic models. In addition, we observed an association between with rs1143704 polymorphism under heterozygous and dominant genetic models (TT+TA vs AA: OR = 1.36, 95%CI = 1.03-1.79, I = 0.0%, P = 0.033). Similar results were found in rs767199 and rs727479 polymorphisms, while null results were found for other polymorphisms.
CONCLUSIONS
This systematic review and meta-analysis suggested that the rs10046, rs1143704, rs767199, and rs727479 polymorphisms in CYP19A1 gene significantly increase AD susceptibility. In addition, our results demonstrated that homozygous TT genotype in rs10046, dominant AA and AG genotypes in rs767199, homozygous TT genotype in rs727479, and dominant TT and TA genotypes in rs1143704 might be the susceptibility genotypes for AD, while no associations were observed between rs1065778, rs1062033, rs1008805, and rs700519 polymorphisms and AD susceptibility.
Topics: Alzheimer Disease; Aromatase; Genetic Predisposition to Disease; Humans
PubMed: 31278540
DOI: 10.1007/s10072-019-04003-1 -
Expert Opinion on Investigational Drugs Dec 2020Pharmacotherapy has a key role in endometriosis treatment and management, however, a significant proportion of patients have only intermittent or limited benefits with...
INTRODUCTION
Pharmacotherapy has a key role in endometriosis treatment and management, however, a significant proportion of patients have only intermittent or limited benefits with current treatment options. Therefore, novel therapeutic approaches are necessary.
AREAS COVERED
This systematic review provides an overview of the efficacy and safety of aromatase inhibitors (AIs) as monotherapies and combination therapies for endometriosis. A systematic literature search was performed from January 1990 to April 2020 in the electronic database MEDLINE, EMBASE, The Cochrane Library, and Web of Science.
EXPERT OPINION
Based on the critical role of estrogens and the rate-limiting step in the production of the estrogens represented by the aromatase enzyme, AIs are a potential therapeutic option for women affected by endometriosis. Nevertheless, further research is needed to clarify the efficacy of AIs in this setting. Adverse effects need to be investigated to clarify the preventive role of add-back therapy. On that basis, AIs should be adopted only as second-line therapy in patients who are refractory to standard treatments in the setting of scientific research. Further studies should define best dosages, appropriate add-back therapies, administration routes, treatment length, and which patients may benefit more from AIs.
Topics: Aromatase Inhibitors; Drug Development; Endometriosis; Estrogens; Female; Humans
PubMed: 33096011
DOI: 10.1080/13543784.2020.1842356 -
Breast (Edinburgh, Scotland) Apr 2022This systematic review aimed to determine the rate and identify correlates of adherence and persistence over five years of treatment with adjuvant endocrine therapy in... (Review)
Review
PURPOSE
This systematic review aimed to determine the rate and identify correlates of adherence and persistence over five years of treatment with adjuvant endocrine therapy in female breast cancer patients.
METHODS
Relevant articles were identified from Medline, Embase, AMED, PsycINFO, International Pharmaceutical Abstracts, and APA PsycArticles. Studies that measured patient adherence in the implementation or persistence phase for a period of at least five years using objective or multiple measures of adherence and investigated correlates of adherence were included. The titles, abstracts and full articles were screened and reviewed by two authors and any discrepancies were discussed with a third author.
RESULTS
Twenty-six studies were included. Mean rate of adherence at five-year for implementation phase was 66.2% (SD = 17.3%), and mean persistence was 66.8% (SD = 14.5%). On average, adherence decreased by 25.5% (SD = 9.3%) from the first to fifth year. Higher rate of adherence was observed through self-report in comparison to database or medical record. Older age, younger age, higher comorbidity index, depression and adverse effects were associated with lower adherence. Treatment with aromatase inhibitors, received chemotherapy, and prior medication use were associated with improved adherence.
CONCLUSION
Adherence to adjuvant endocrine therapy decreased from the first to fifth year of treatment. On average, one-third of patients were not adherent to treatment by the fifth year. Nineteen recurring factors were found to be significantly associated with long-term adherence in multiple studies. Further research using objective or multiple measures of adherence are needed to improve validity of results.
Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Humans; Medication Adherence; Neoplasm Recurrence, Local; Patient Compliance
PubMed: 35121501
DOI: 10.1016/j.breast.2022.01.012 -
Reproductive Biomedicine Online Feb 2022The preservation of fertility in women of childbearing age with breast cancer is challenging because the time for ovarian stimulation is restricted and only a limited... (Meta-Analysis)
Meta-Analysis Review
The preservation of fertility in women of childbearing age with breast cancer is challenging because the time for ovarian stimulation is restricted and only a limited number of oocytes can be retrieved before gonadotoxic therapies. The aim of this meta-analysis was to evaluate the fertility preservation outcomes after ovarian stimulation with various protocols in women with breast cancer. PubMed, Embase and the Cochrane Library were searched. Twenty-two studies comparing the outcomes of women with breast cancer receiving random-start ovarian stimulation or conventional protocol; single or double ovarian stimulation cycles; and coadministration of aromatase inhibitors or tamoxifen were included. Random-start ovarian stimulation resulted in a comparable number of retrieved oocytes to the conventional protocol. Two ovarian stimulation cycles had significantly higher numbers of total retrieved oocytes than one cycle (mean difference 7.91, 95% confidence interval [CI] 3.42 to 12.40). Coadministration of letrozole and tamoxifen showed similar results for retrieved oocytes to those without. A significantly lower peak serum oestradiol concentration was observed in letrozole-based groups than in letrozole-free groups (mean difference -1.22; 95% CI -1.42 to -1.02). In conclusion, this study indicated that implementing random-start protocols to shorten the duration of waiting for ovarian stimulation, applying two ovarian stimulation cycles, and coadministration of letrozole can lead to more desirable outcomes.
Topics: Breast Neoplasms; Cryopreservation; Female; Fertility Preservation; Humans; Letrozole; Oocytes; Ovulation Induction; Tamoxifen
PubMed: 34656436
DOI: 10.1016/j.rbmo.2021.08.003 -
Breast (Edinburgh, Scotland) Aug 2021Hormone Therapy (HT) reduces the risk of breast cancer recurrence and mortality in women with breast cancer. Despite these clinical benefits, rates of HT non-adherence... (Review)
Review
BACKGROUND
Hormone Therapy (HT) reduces the risk of breast cancer recurrence and mortality in women with breast cancer. Despite these clinical benefits, rates of HT non-adherence and non-persistence are high. Research suggests this may be due to the impact of HT side effects. However, little research has explored the individual contribution of side effects to non-adherence and non-persistence behaviours, thereby hindering the implementation of targeted intervention strategies. Our aim is to review the published literature on breast cancer survivors' lived experiences of HT side effects and explore how these may be related to non-adherence and non-persistence behaviour.
METHODS
Electronic searches were conducted from inception to May 2020, utilising Cochrane CENTRAL, Medline, Embase, Web of Science and PsycINFO databases. Searches included a combination of terms related to breast cancer, adherence, hormone therapy and side effects.
RESULTS
Sixteen eligible papers were identified, and study quality was high. Data were thematically synthesised into four analytical themes, which encompassed 13 descriptive sub-themes: 'Daily impact of side-effects', 'Role of Health Care Professionals', 'Managing HT side-effects', and 'Weighing up the pros and cons'.
CONCLUSIONS
HT side effects significantly impact breast cancer survivor's quality of life. A lack of support from healthcare providers leads to self-management strategies, which negatively affects adherence and persistence behaviour.
Topics: Breast Neoplasms; Cancer Survivors; Female; Hormones; Humans; Medication Adherence; Neoplasm Recurrence, Local; Quality of Life
PubMed: 34049260
DOI: 10.1016/j.breast.2021.05.005 -
Gynecological Endocrinology : the... Feb 2021Previously, many studies investigated the association between CYP19 rs2414096(G > A) and susceptibility to develop PCOS. However, results had been inconsistent.... (Meta-Analysis)
Meta-Analysis
Previously, many studies investigated the association between CYP19 rs2414096(G > A) and susceptibility to develop PCOS. However, results had been inconsistent. Therefore, our systematic review and meta-analysis aimed to identify the association between CYP19 rs2414096 and PCOS risk. A systematic literature search was done from database PubMed, Google Scholar, Science Direct, and Cochrane Library up to July 15 2020 and statistical analysis was performed by RevMan5.3. A total of seven studies comprised of 1414 PCOS cases and 1276 controls were included in the current meta-analysis. The pooled analysis showed that overall, there is a significant association between CYP19 rs2414096(G > A) and risk of PCOS (OR = 0.74, 95% CI= 0.62-0.88, = .0008). In dominant model, GG + AG vs GG and recessive genetic model AA vs AG + GG found a significant association (OR = 1.60,95% CI = 1.10-2.31, = .01; OR = 0.65,95% CI = 0.45-0.93, = .02) respectively which indicates that GG phenotype might be risk factor for PCOS development. In stratified subgroup analysis, there was significant association between CYP19 rs2414096 polymorphism and PCOS risk for non-Indian population only while no association was found with Indian population. Present meta-analysis studies indicate that CYP19 rs2414096 is associated with PCOS risk and important in pathogenesis of PCOS for many populations but for Indian population more studies are required as Indian population comprises of various subpopulations genetically isolated since long.
Topics: Aromatase; Female; Genetic Predisposition to Disease; Humans; Polycystic Ovary Syndrome
PubMed: 32856958
DOI: 10.1080/09513590.2020.1813274 -
Cancer Medicine Jan 2023Breast cancer (BC) is a common type of cancer in women. Advances in therapy options have resulted in higher overall survival rates but side effects of cancer treatment... (Review)
Review
INTRODUCTION
Breast cancer (BC) is a common type of cancer in women. Advances in therapy options have resulted in higher overall survival rates but side effects of cancer treatment are increasingly in the spotlight. The beneficial effects of anti-oestrogen therapy with tamoxifen and letrozole in the prevention of BC recurrence are well documented. While the most common side-effects of this therapy are well-defined, less is known about its effects on thyroid function. In women treated for early BC, an average of 1-5 kg weight gain has been observed after treatment with chemotherapy/anti-oestrogens. We aim to evaluate the current knowledge on the side effects of tamoxifen and letrozole treatments on thyroid function, followed by its potential influence on the observed weight gain.
METHODS
We searched PubMed and found 16 publications on thyroid function and tamoxifen treatment in pre- and post-menopausal women with early- and advanced BC, whereas five publications on letrozole treatment in post-menopausal women with advanced BC.
RESULTS
According to the current literature, there is an overall tendency towards a mild and transient thyroid dysfunction, that is, subclinical hypothyroidism in tamoxifen-treated patients. Only one publication reported further significant changes in thyroid hormones beyond one year of tamoxifen treatment. No significant changes in thyroid function have been observed among letrozole-treated patients.
CONCLUSION
Tamoxifen-treated patients can develop mild and transient thyroid dysfunction within the first 12 months, yet further significant changes in thyroid function beyond one year of tamoxifen treatment have been reported in a single study. There is no evidence of thyroid dysfunction in letrozole-treated patients. Current literature does not focus on subclinical hypothyroidism as a possible cause of weight gain in patients with BC. Subgrouping of BC patients and studies with a longer observation of thyroid hormones and weight changes during and after anti-oestrogen treatment are needed to further elucidate how anti-oestrogens affect thyroid function.
Topics: Humans; Female; Letrozole; Breast Neoplasms; Tamoxifen; Aromatase Inhibitors; Nitriles; Triazoles; Neoplasm Recurrence, Local; Estrogens; Hypothyroidism; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant
PubMed: 35748065
DOI: 10.1002/cam4.4949 -
Clinical Breast Cancer Apr 2022Concerns around pharmacological interaction between tamoxifen and antidepressants have resulted in evidence-base guidelines that recommend avoidance or caution with... (Review)
Review
Concerns around pharmacological interaction between tamoxifen and antidepressants have resulted in evidence-base guidelines that recommend avoidance or caution with concurrent use. It remains unclear however whether this interaction is clinically important. A systematic review of studies comparing endocrine therapy (including tamoxifen and aromatase inhibitors) alone or concurrent with antidepressants in breast cancer patients was performed. The literature search sought studies within MEDLINE, EMBASE, and the Cochrane Collaboration Library published from database inception until December 1, 2020. Outcomes of interest included recurrence, breast cancer-specific survival, overall mortality, quality of life, and treatment compliance. Studies were assessed with the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle Ottawa tool for case-control and cohort studies. From 695 citations, we included 15 studies (2 randomized controlled trials [255 patients], 10 retrospective cohort studies [75,678 patients], and 3 case-control studies [18,836 patients]). While between-study clinical and methodologic differences (including analysis of confounding variables) precluded formal meta-analysis, findings from included studies did not find consistent evidence that concurrent use of antidepressants (including paroxetine) with tamoxifen therapy has negative impacts on the outcomes of interest. In this systematic review, despite data from nearly 100,000 patients, concurrent use of tamoxifen and antidepressants showed no consistent negative effect on clinical outcomes. Given the recognized harm to patients of changing either endocrine therapy or antidepressants to avoid concurrent use, current evidence-based guidelines should be updated accordingly. More rigorously designed pharmacoepidemiologic studies are needed.
Topics: Antidepressive Agents; Breast Neoplasms; Female; Humans; Practice Guidelines as Topic; Quality of Life; Retrospective Studies; Tamoxifen
PubMed: 34740542
DOI: 10.1016/j.clbc.2021.10.003