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Breast Cancer (Tokyo, Japan) Jan 2018In patients with hormone receptor-positive postmenopausal of early stage breast cancer, adjuvant endocrine monotherapies include letrozole, anastrozole, exemestane,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In patients with hormone receptor-positive postmenopausal of early stage breast cancer, adjuvant endocrine monotherapies include letrozole, anastrozole, exemestane, toremifene and tamoxifen. But the optimum regimen remains controversial.
METHODS
PubMed, Cochrane Database and ClinicalTrials.gov were systematically reviewed of abstract for randomized-controlled trials (RCTs) to assess the efficacy of tamoxifen, letrozole, exemestane, anastrozle and toremifene for postmenopausal patients with hormone-receptor positive (HR+), who have not received prior therapy for early stage breast cancer. The outcomes were measured by disease-free survival (DFS) and overall survival (OS). We evaluated relative hazard ratios (HRs) for death of different therapies by combination hazard ratios for death of included trials. The SUCRA values were used to evaluate the rankings of efficacy for these monotherapies.
RESULTS
A total of fourteen studies including 19,517 patients in our research were absorbed and estimated. The superiority of efficacy for DFS were 5-year letrozole and 10-year tamoxifen (SUCRA values 0.743/0.657) in all comparisons. A more efficient SUCRA values for OS were 5-year Exemestane, 5-year letrozole and 10-year tamoxifen (0.756/0.677/0.669).
CONCLUSIONS
Clinically important differences exist between commonly prescribed different adjuvant endocrine monotherapy regimens for both efficacy and acceptability in favor of exemestane and letrozole. 10-year tamoxifen for early breast cancer patients is noninferior to 5-year anastrozle, and might be the best choice where aromatase inhibitors (AIs) are not easy to acquire.
Topics: Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Network Meta-Analysis; Postmenopause; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone
PubMed: 28755088
DOI: 10.1007/s12282-017-0794-8 -
The Cochrane Database of Systematic... Jan 2017Fulvestrant is a selective oestrogen receptor down-regulator (SERD), which by blocking proliferation of breast cancer cells, is an effective endocrine treatment for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fulvestrant is a selective oestrogen receptor down-regulator (SERD), which by blocking proliferation of breast cancer cells, is an effective endocrine treatment for women with hormone-sensitive advanced breast cancer. The goal of such systemic therapy in this setting is to reduce symptoms, improve quality of life, and increase survival time.
OBJECTIVES
To assess the efficacy and safety of fulvestrant for hormone-sensitive locally advanced or metastatic breast cancer in postmenopausal women, as compared to other standard endocrine agents.
SEARCH METHODS
We searched the Cochrane Breast Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov on 7 July 2015. We also searched major conference proceedings (American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer Symposium) and practice guidelines from major oncology groups (ASCO, European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network, and Cancer Care Ontario). We handsearched reference lists from relevant studies.
SELECTION CRITERIA
We included for analyses randomised controlled trials that enrolled postmenopausal women with hormone-sensitive advanced breast cancer (TNM classifications: stages IIIA, IIIB, and IIIC) or metastatic breast cancer (TNM classification: stage IV) with an intervention group treated with fulvestrant with or without other standard anticancer therapy.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from trials identified in the searches, conducted 'Risk of bias' assessments of the included studies, and assessed the overall quality of the evidence using the GRADE approach. Outcome data extracted from these trials for our analyses and review included progression-free survival (PFS) or time to progression (TTP) or time to treatment failure, overall survival, clinical benefit rate, toxicity, and quality of life. We used the fixed-effect model for meta-analysis where possible.
MAIN RESULTS
We included nine studies randomising 4514 women for meta-analysis and review. Overall results for the primary endpoint of PFS indicated that women receiving fulvestrant did at least as well as the control groups (hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.89 to 1.02; P = 0.18, I= 56%, 4258 women, 9 studies, high-quality evidence). In the one high-quality study that tested fulvestrant at the currently approved and now standard dose of 500 mg against anastrozole, women treated with fulvestrant 500 mg did better than anastrozole, with a HR for TTP of 0.66 (95% CI 0.47 to 0.93; 205 women) and a HR for overall survival of 0.70 (95% CI 0.50 to 0.98; 205 women). There was no difference in PFS whether fulvestrant was used in combination with another endocrine therapy or in the first- or second-line setting, when compared to control treatments: for monotherapy HR 0.97 (95% CI 0.90 to 1.04) versus HR 0.87 (95% CI 0.77 to 0.99) for combination therapy when compared to control, and HR 0.93 (95% CI 0.84 to 1.03) in the first-line setting and HR 0.96 (95% CI 0.88 to 1.04) in the second-line setting.Overall, there was no difference between fulvestrant and control treatments in clinical benefit rate (risk ratio (RR) 1.03, 95% CI 0.97 to 1.10; P = 0.29, I = 24%, 4105 women, 9 studies, high-quality evidence) or overall survival (HR 0.97, 95% CI 0.87 to 1.09, P = 0.62, I = 66%, 2480 women, 5 studies, high-quality evidence). There was no significant difference in vasomotor toxicity (RR 1.02, 95% CI 0.89 to 1.18, 3544 women, 8 studies, high-quality evidence), arthralgia (RR 0.96, 95% CI 0.86 to 1.09, 3244 women, 7 studies, high-quality evidence), and gynaecological toxicities (RR 1.22, 95% CI 0.94 to 1.57, 2848 women, 6 studies, high-quality evidence). Four studies reported quality of life, none of which reported a difference between the fulvestrant and control arms, though specific data were not presented.
AUTHORS' CONCLUSIONS
For postmenopausal women with advanced hormone-sensitive breast cancer, fulvestrant is at least as effective and safe as the comparator endocrine therapies in the included studies. However, fulvestrant may be potentially more effective than current therapies when given at 500 mg, though this higher dosage was used in only one of the nine studies included in the review. We saw no advantage with combination therapy, and fulvestrant was equally as effective as control therapies in both the first- and second-line setting. Our review demonstrates that fulvestrant is a safe and effective systemic therapy and can be considered as a valid option in the sequence of treatments for postmenopausal women with hormone-sensitive advanced breast cancer.
Topics: Anastrozole; Antineoplastic Agents, Hormonal; Breast Neoplasms; Disease-Free Survival; Estradiol; Female; Fulvestrant; Humans; Neoplasms, Hormone-Dependent; Nitriles; Randomized Controlled Trials as Topic; Triazoles
PubMed: 28043088
DOI: 10.1002/14651858.CD011093.pub2 -
Annals of Oncology : Official Journal... Mar 2017Aromatase inhibitors (AIs) have been associated with cardiovascular disease in adjuvant randomized controlled trials (RCTs) comparing these drugs to tamoxifen. However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Aromatase inhibitors (AIs) have been associated with cardiovascular disease in adjuvant randomized controlled trials (RCTs) comparing these drugs to tamoxifen. However, it is unclear whether this risk is real or due to cardioprotective effects of tamoxifen. To address this question, we conducted a systematic review and meta-analysis of all RCTs of AIs and tamoxifen in adjuvant and extended adjuvant setting.
PATIENTS AND METHODS
We searched PubMed, Embase (OVID), Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from inception to June 2016 for all RCTs comparing cardiovascular and cerebrovascular safety of AIs to tamoxifen, AIs to placebo or no-treatment, or tamoxifen to placebo or no-treatment in the adjuvant or extended adjuvant setting. Relative risks (RRs) were pooled using DerSimonian and Laird random-effects models with analyses stratified by RCT design.
RESULTS
A total of 19 RCTs were included in the meta-analysis (n = 62 345). In the adjuvant setting, AIs were associated with a 19% (RR: 1.19, 95% confidence interval [CI]: 1.07-1.34) increased risk of cardiovascular events compared with tamoxifen. AIs were not associated with an increased risk compared with placebo in the extended-adjuvant setting (RR: 1.01, 95% CI: 0.85-1.20). In the adjuvant setting, tamoxifen was associated with a 33% (RR: 0.67, 95% CI: 0.45-0.98) decreased risk compared with placebo or no-treatment. The results from extended adjuvant RCTs comparing tamoxifen to placebo were inconclusive but suggestive of a small protective effect (RR: 0.91, 95% CI: 0.77-1.07).
CONCLUSIONS
The increased risk of cardiovascular events with AIs relative to tamoxifen is likely the result of cardioprotective effects of the latter. This new evidence should be considered when assessing the benefits and risks of AIs in the treatment of breast cancer.
Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Cardiotoxicity; Female; Humans; Postmenopause; Randomized Controlled Trials as Topic; Risk Factors; Tamoxifen
PubMed: 27998966
DOI: 10.1093/annonc/mdw673 -
World Journal of Clinical Oncology Aug 2016To evaluate the current role of sorafenib, an oral multikinase inhibitor in the treatment of breast cancer.
AIM
To evaluate the current role of sorafenib, an oral multikinase inhibitor in the treatment of breast cancer.
METHODS
An extensive search of the literature until March 2016 was carried out in Medline and clinicaltrials.gov, by using the search terms "sorafenib" and "breast cancer". Papers found were checked for further relevant publications. Overall, 21 relevant studies were found, 18 in advanced breast cancer (16 in stage IV and two in stages III-IV) and three in early breast cancer.
RESULTS
Among studies in advanced breast cancer, there were two trials with sorafenib as monotherapy, four trials of sorafenib in combination with taxanes, two in combination with capecitabine, one with gemcitabine and/or capecitabine, one with vinorelbine, one with bevacizumab, one with pemetrexed and one with ixabepilone, three trials of sorafenib in combination with endocrine therapy and two trials in women with brain metastases undergoing whole brain radiotherapy. In addition, there was one trial of sorafenib added to standard chemotherapy in the adjuvant setting, and two trials in the neoadjuvant setting. In general, sorafenib was well tolerated in breast cancer patients, though its dosage had to be adjusted in some trials, and discontinuation rates were high, particularly for the combination of sorafenib with anastrozole. Sorafenib monotherapy and combinations with taxanes, bevacizumab and ixabepilone showed inadequate efficacy, while efficacy results from combinations with gemcitabine and/or capecitabine and possibly tamoxifen were more promising.
CONCLUSION
At present, sorafenib should not be used for the treatment of breast cancer outside of clinical trials and more clinical data are needed in order to support its standard use in breast cancer therapy.
PubMed: 27579253
DOI: 10.5306/wjco.v7.i4.331 -
JBRA Assisted Reproduction May 2016The aim of this study as to analyze published evidence regarding the effectiveness of aromatase inhibitor therapy on improving spermatogenesis in infertile men. We... (Meta-Analysis)
Meta-Analysis Review
The aim of this study as to analyze published evidence regarding the effectiveness of aromatase inhibitor therapy on improving spermatogenesis in infertile men. We carried out a systematic review of randomized controlled trials. The date of the most recent search was October 4, 2015. Two authors independently selected relevant clinical trials, assessing their methodological quality and extracting data. Three studies were included in this review with a total of 100 participants; however, we were able to include data from only 54 participants in the analysis. In the representation of meta-analysis with a single study comparing testolactone versus placebo, related to the hormone concentrations, there was a statistically significance difference favoring the use of testolactone for Luteinizing Hormone (LH); Estrogen (E2); free Testosterone (free T); free Estrogen (free E2); 17-Hydroxyprogesterone (17OHP); prolactin (PRL). In another analysis from a single study comparing letrozole versus anastrozole, there was also a statistically significance difference favoring the use of letrozole for the increase in both the sperm count and LH. There is only low quality evidence regarding the effectiveness of aromatase inhibitor therapy in infertile men. Further trials are needed with standardized interventions and outcomes.
Topics: Aromatase Inhibitors; Azoospermia; Humans; Male; Oligospermia; Randomized Controlled Trials as Topic
PubMed: 27244767
DOI: 10.5935/1518-0557.20160019 -
Integrative Cancer Therapies Jun 2016Background Lower breast density (BD) is associated with lower risk of breast cancer and may serve as a biomarker for the efficacy of chemopreventive strategies. This... (Meta-Analysis)
Meta-Analysis
Background Lower breast density (BD) is associated with lower risk of breast cancer and may serve as a biomarker for the efficacy of chemopreventive strategies. This review explores parameters that are thought to be associated with lower BD. We conducted a systematic review of articles published to date using the PRISMA strategy. Articles that assessed change in BD with estrogen-receptor modulators (tamoxifene [TAM], raloxifene [RLX], and tibolone) and aromatase inhibitors (AIs), as well as cross-sectional and longitudinal studies (LSs) that assessed association between BD and physical activity (PA) or diet were reviewed. Results Ten studies assessed change in BD with TAM; all reported TAM-mediated BD decreases. Change in BD with RLX was assessed by 11 studies; 3 reported a reduction in BD. Effect of tibolone was assessed by 5 RCTs; only 1 reported change in BD. AI-mediated BD reduction was reported by 3 out of 10 studies. The association between PA and BD was assessed by 21 studies; 4 reported an inverse association. The relationship between diet and BD was assessed in 34 studies. All studies on calcium and vitamin D as well as vegetable intake reported an inverse association with BD in premenopausal women. Two RCTs demonstrated BD reduction with a low-fat, high-carbohydrate intervention. Conclusion TAM induces BD reduction; however, the effect of RLX, tibolone, and AIs on BD is unclear. Although data on association between diet and BD in adulthood are contradictory, intake of vegetables, vitamin D, and calcium appear to be associated with lower BD in premenopausal women.
Topics: Adult; Aged; Aged, 80 and over; Aromatase Inhibitors; Breast; Breast Density; Breast Neoplasms; Cross-Sectional Studies; Diet; Exercise; Female; Humans; Longitudinal Studies; Middle Aged; Selective Estrogen Receptor Modulators; Vitamin D
PubMed: 27130722
DOI: 10.1177/1534735416628343 -
PloS One 2015Gynecomastia and/or mastodynia is a common medical problem in patients receiving antiandrogen (bicalutamide or flutamide) treatment for prostate cancer; up to 70% of... (Review)
Review
INTRODUCTION
Gynecomastia and/or mastodynia is a common medical problem in patients receiving antiandrogen (bicalutamide or flutamide) treatment for prostate cancer; up to 70% of these patients result to be affected; furthermore, this can jeopardise patients' quality of life.
AIMS
To systematically review the quality of evidence of the current literature regarding treatment options for bicalutamide-induced gynecomastia, including efficacy, safety and patients' quality of life.
METHODS
The PubMed, Medline, Scopus, The Cochrane Library and SveMed+ databases were systematically searched between January 1, 2000 and December 31, 2014. All searches were undertaken between January and February 2015. The search phrase used was:"gynecomastia AND treatment AND prostate cancer". Two reviewers assessed 762 titles and abstracts identified. The search and review process was done in accordance with the PRISMA statement. The PICOS (patients, intervention, comparator, outcomes and study design) process was used to specify inclusion criteria. Quality of evidence was rated according to GRADE.
MAIN OUTCOME MEASURES
Primary outcomes were: treatment effects, number of complications and side effects. Secondary outcome was: Quality of Life.
RESULTS
Eleven studies met the inclusion criteria and are analysed in this review. Five studies reported pharmacological intervention with tamoxifen and/or anastrozole, either as prophylactic or therapeutic treatment. Four studies reported radiotherapy as prophylactic and/or therapeutic treatment. Two studies compared pharmacological treatment to radiotherapy. Most of the studies were randomized with varying risk of bias. According to GRADE, quality of evidence was moderate to high.
CONCLUSIONS
Bicalutamide-induced gynecomastia and/or mastodynia can effectively be managed by oral tamoxifen (10-20 mg daily) or radiotherapy without relevant side effects. Prophylaxis or therapeutic treatment with tamoxifen results to be more effective than radiotherapy.
Topics: Androgen Antagonists; Gynecomastia; Humans; Male; Meta-Analysis as Topic; Prostatic Neoplasms; Quality of Life
PubMed: 26308532
DOI: 10.1371/journal.pone.0136094 -
Journal of Cancer 2015Inhibition of aberrantly activated pathways cross-talking with hormone receptor (HR) improves response to endocrine therapy in patients with HR-positive advanced breast... (Review)
Review
Inhibition of aberrantly activated pathways cross-talking with hormone receptor (HR) improves response to endocrine therapy in patients with HR-positive advanced breast cancer. We performed a Pubmed database systematic review to ascertain the existence of a better clinical response when combining endocrine therapy with targeted agents in the neoadjuvant setting. Preclinical studies or trials evaluating toxicity were excluded. We found nine phase II trials that fulfilled the research criteria. The endocrine agents used were third generation aromatase inhibitors (AIs), anastrozole, letrozole or exemestane. The investigated targeted agents were inhibitors of tyrosine kinase receptors such as gefitinib, imatinib or trastuzumab/lapatinib, inhibitors of mTOR, such as everolimus, inhibitors of COX-2, such as celecoxib, and inhibitors of angiogenesis, such as bevacizumab. The response rate (RR) observed combining endocrine and targeted agents ranged between 36% and 90%. Overall the studies failed to show a remarkable advantage in RR in the combination group compared to historical control subjects receiving AIs alone.
PubMed: 26000050
DOI: 10.7150/jca.11566 -
American Journal of Clinical Oncology Aug 2014The addition of adjuvant chemotherapy to hormonal therapy is recommended for patients with estrogen receptor-positive (ER+), node-positive (N+) early breast cancer... (Meta-Analysis)
Meta-Analysis Review
The addition of adjuvant chemotherapy to hormonal therapy is recommended for patients with estrogen receptor-positive (ER+), node-positive (N+) early breast cancer (EBC). Some of these patients, however, are not likely to benefit from treatment and may, therefore, be overtreated while also incurring unnecessary treatment-related adverse events and health care costs. The 21-gene Recurrence Score assay has been clinically validated and recommended for use in patients with ER+, node-negative (N0) EBC to assess the 10-year risk of distant disease recurrence and predict the likelihood of response to adjuvant chemotherapy. A growing body of evidence from several large phase III clinical trials reports similar findings in patients with ER+, N+ EBC. A systematic review of published literature from key clinical trials that have used the 21-gene breast cancer assay in patients with ER+, N+ EBC was performed. The Recurrence Score has been shown to be an independent predictor of disease-free survival, overall survival, and distant recurrence-free interval in patients with ER+, N+ EBC. Outcomes from decision impact and health economics studies further indicate that the Recurrence Score affects physician treatment recommendations equally in patients with N+ or N0 disease. It also indicates that a reduction in Recurrence Score-directed chemotherapy is cost-effective. There is a large body of evidence to support the use of the 21-gene assay Recurrence Score in patients with N+ EBC. Use of this assay could help guide treatment decisions for patients who are most likely to receive benefit from chemotherapy.
Topics: Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials, Phase III as Topic; Disease-Free Survival; Female; Genetic Markers; Humans; Nitriles; Predictive Value of Tests; Prognosis; Receptors, Estrogen; Reproducibility of Results; Tamoxifen; Treatment Outcome; Triazoles; Validation Studies as Topic
PubMed: 24853663
DOI: 10.1097/COC.0000000000000086 -
Journal of Clinical Oncology : Official... Jul 2014To provide evidence-based recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)... (Review)
Review
Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline.
PURPOSE
To provide evidence-based recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.
METHODS
The American Society of Clinical Oncology convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic literature review from January 2009 to October 2012. Outcomes of interest included overall survival, progression-free survival (PFS), and adverse events.
RESULTS
A total of 16 trials met the systematic review criteria. The CLEOPATRA trial found survival and PFS benefits for docetaxel, trastuzumab, and pertuzumab in first-line treatment, and the EMILIA trial found survival and PFS benefits for trastuzumab emtansine (T-DM1) in second-line treatment. T-DM1 also showed a third-line PFS benefit. One trial reported on duration of HER2-targeted therapy, and three others reported on endocrine therapy for patients with HER-positive advanced breast cancer.
RECOMMENDATIONS
HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and T-DM1 for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations or T-DM1 (if not previously administered) and may offer pertuzumab, if the patient has not previously received it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive/progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone.
Topics: Ado-Trastuzumab Emtansine; Anastrozole; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Clinical Trials as Topic; Comorbidity; Docetaxel; Drug Administration Schedule; Evidence-Based Medicine; Female; Health Status Disparities; Healthcare Disparities; Humans; Lapatinib; Letrozole; Maytansine; Molecular Targeted Therapy; Nitriles; Quinazolines; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Societies, Medical; Taxoids; Trastuzumab; Treatment Outcome; Triazoles; United States
PubMed: 24799465
DOI: 10.1200/JCO.2013.54.0948