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JNCI Cancer Spectrum Feb 2021Higher mammographic breast density (MBD) is associated with an increased risk of breast cancer when compared with lower MBD, especially in premenopausal women. However,...
BACKGROUND
Higher mammographic breast density (MBD) is associated with an increased risk of breast cancer when compared with lower MBD, especially in premenopausal women. However, little is known about the effectiveness of chemoprevention agents in reducing MBD in premenopausal women without a history of breast cancer. Findings from this review should provide insight on how to target MBD in breast cancer prevention in premenopausal women with dense breasts.
METHODS
We searched 9 electronic databases for clinical trials in English, Spanish, French, or German published until January 2020. Articles evaluating the association of pharmacological agents and MBD were included. Data were extracted on methods, type and dose of intervention, outcomes, side effects, and follow up. Quality of the studies was assessed using the US Preventive Services Task Force criteria.
RESULTS
We identified 7 clinical trials evaluating the associations of 6 chemoprevention agents with changes in MBD in premenopausal women without history of breast cancer. The studies evaluated selective estrogen-receptor modulators (n = 1); gonadotropin-releasing hormone agonists (n = 2); isoflavones (n = 1); vitamin D (n = 1); and Boswellia, betaine, and mayo-inositol compound (n = 1). Hormonal interventions were associated with net reductions in percent density (tamoxifen [13.4%], leuprolide acetate [8.9%], and goserelin [2.7%]), whereas nonhormonal (vitamin D and isoflavone) interventions were not. However, MBD returned to preintervention baseline levels after cessation of gonadotropin-releasing hormone agonists.
CONCLUSIONS
A limited number of chemoprevention agents have been shown to reduce MBD in premenopausal women. Identification of new and well-tolerated chemoprevention agents targeting MBD and larger studies to confirm agents that have been studied in small trials are urgent priorities for primary breast cancer prevention in premenopausal women with dense breasts.
Topics: Anticarcinogenic Agents; Betaine; Boswellia; Breast Density; Drug Combinations; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Inositol; Isoflavones; Leuprolide; Mammography; Premenopause; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Tamoxifen; Vitamin D; Vitamins
PubMed: 33554041
DOI: 10.1093/jncics/pkaa125 -
Journal of Bone Oncology Oct 2019Hormonal therapies for receptor positive-breast and prostate cancer patients have shown clinical efficacy but also several side effects including osteoporosis, loss of... (Review)
Review
Hormonal therapies for receptor positive-breast and prostate cancer patients have shown clinical efficacy but also several side effects including osteoporosis, loss of bone mass and increased fracture risk. Denosumab represents an anti RANKL (receptor activator of nuclear factor-kB ligand) monoclonal anti-body acting as inhibitor of osteoclasts formation, function, and survival, then increasing bone mass. Herein, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the role of Denosumab in saving bone health in prostate and breast cancer patients receiving respectively androgen deprivation therapy and adjuvant endocrine therapy. Moreover, selected patients have to be treated with Denosumab at the dose of 60 mg every six month or placebo. Outcomes studied included the bone mass density (BMD) increase at 24 and 36 months, BMD loss, reduction of fractures risk (in particular vertebral) at 24 and 36 months and safety (overall, serious adverse events - SAEs and discontinuation rate). Our results showed a reduction of the BMD loss up to 36 months both at the lumbar and femoral level and a BMD increase both at 24 and 36 months. It was also found a reduction in the number of new vertebral and femoral fractures at 24 and 36 months. Finally, our pooled analysis showed that Denosumab did not affect both the SAEs and therapy discontinuation risk. In conclusion, Denosumab administration can be considered effective and safe in the prevention and management of the above mentioned adverse events related to hormonal therapies designed for breast and prostate tumors.
PubMed: 31440444
DOI: 10.1016/j.jbo.2019.100252 -
Breast Cancer Research : BCR Oct 2016Breast density, the amount of fibroglandular tissue in the adult breast for a women's age and body mass index, is a strong biomarker of susceptibility to breast cancer,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Breast density, the amount of fibroglandular tissue in the adult breast for a women's age and body mass index, is a strong biomarker of susceptibility to breast cancer, which may, like breast cancer risk itself, be influenced by events early in life. In the present study, we investigated the association between pre-natal exposures and breast tissue composition.
METHODS
A sample of 500 young, nulliparous women (aged approximately 21 years) from a U.K. pre-birth cohort underwent a magnetic resonance imaging examination of their breasts to estimate percent water, a measure of the relative amount of fibroglandular tissue equivalent to mammographic percent density. Information on pre-natal exposures was collected throughout the mothers' pregnancy and shortly after delivery. Regression models were used to investigate associations between percent water and pre-natal exposures. Mediation analysis, and a systematic review and meta-analysis of the published literature, were also conducted.
RESULTS
Adjusted percent water in young women was positively associated with maternal height (p for linear trend [p ] = 0.005), maternal mammographic density in middle age (p = 0.018) and the participant's birth size (p < 0.001 for birthweight). A 1-SD increment in weight (473 g), length (2.3 cm), head circumference (1.2 cm) and Ponderal Index (4.1 g/cm) at birth were associated with 3 % (95 % CI 2-5 %), 2 % (95 % CI 0-3 %), 3 % (95 % CI 1-4 %) and 1 % (95 % CI 0-3 %), respectively, increases in mean adjusted percent water. The effect of maternal height on the participants' percent water was partly mediated through birth size, but there was little evidence that the effect of birthweight was primarily mediated via adult body size. The meta-analysis supported the study findings, with breast density being positively associated with birth size.
CONCLUSIONS
These findings provide strong evidence of pre-natal influences on breast tissue composition. The positive association between birth size and relative amount of fibroglandular tissue indicates that breast density and breast cancer risk may share a common pre-natal origin.
Topics: Adult; Breast Density; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Mammary Glands, Human; Maternal Exposure; Population Surveillance; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; United Kingdom; Young Adult
PubMed: 27729066
DOI: 10.1186/s13058-016-0751-z -
Pharmaceutical Biology Dec 2023Chinese medicinal herbs (CMH) have been considered a potentially efficacious approach for patients with breast cancer that experience adverse effects from endocrine... (Meta-Analysis)
Meta-Analysis
Chinese medicinal herbs for reducing endocrine therapy-induced side effects in patients with hormone receptor-positive breast cancer: a systematic review and meta-analysis.
CONTEXT
Chinese medicinal herbs (CMH) have been considered a potentially efficacious approach for patients with breast cancer that experience adverse effects from endocrine treatment.
OBJECTIVE
To investigate the impact of CMH on endocrine therapy-induced side effects in patients with hormone receptor-positive (HR+) breast cancer.
METHODS
Ten databases (e.g., PubMed, Web of Science, Cochrane Library, China National Knowledge Information Database and other databases) were searched up to 20 May 2022. The search terms included Chinese herb, breast cancer, endocrine therapy, clinical trial and their mesh terms. The study selection and data extraction were performed by two independent reviewers. The risk of bias was evaluated using the Cochrane risk of bias method.
RESULTS
A total of 31 studies with 2288 patients were included. There were significant improvements in bone mineral density (BMD) [lumbar BMD ( 0.08, 95% CI 0.07 to 0.09, < 0.00001) and femoral neck BMD ( 0.08, 95% CI 0.07 to 0.10, < 0.00001)] and bone gal protein (BGP) ( 0.24, 95% CI 0.17 to 0.31, < 0.00001), with a significant reduction in triglycerides (MD -0.53, 95% CI -1.00 to -0.07, < 0.05) and no effect on estradiol levels (MD 0.90, 95% CI -0.31 to 2.12, = 0.15).
CONCLUSIONS
CMH combined with complementary therapy can moderately reduce endocrine therapy-induced side effects, including bone loss and dyslipidemia in patients with HR + breast cancer, revealing the potential role of CMH in treating (HR+) breast cancer. More high-quality RCTs are warranted to further validate the effectiveness and safety of CMH.
Topics: Humans; Female; Breast Neoplasms; Plants, Medicinal; Antineoplastic Agents; Bone Density; China
PubMed: 37096936
DOI: 10.1080/13880209.2023.2203193 -
Women's Health Issues : Official... 2015A review was conducted to summarize the current evidence and gaps in the literature on geographic access to mammography and its relationship to breast cancer-related... (Review)
Review
INTRODUCTION
A review was conducted to summarize the current evidence and gaps in the literature on geographic access to mammography and its relationship to breast cancer-related outcomes.
METHODS
Ovid, Medline, and PubMed were searched for articles published between January 1, 2000, and April 1, 2013, using Medical Subject Headings and key terms representing geographic accessibility and breast cancer-related outcomes. Owing to a paucity of breast cancer treatment and mortality outcomes meeting the criteria (N = 6), outcomes were restricted to breast cancer screening and stage at diagnosis. Studies included one or more of the following types of geographic accessibility measures: capacity, density, distance, and travel time. Study findings were grouped by outcome and type of geographic measure.
RESULTS
Twenty-one articles met the inclusion criteria. Fourteen articles included stage at diagnosis as an outcome, five included mammography use, and two included both. Geographic measures of mammography accessibility varied widely across studies. Findings also varied, but most articles found either increased geographic access to mammography associated with increased use and decreased late-stage at diagnosis or no association.
CONCLUSION
The gaps and methodologic heterogeneity in the literature to date limit definitive conclusions about an underlying association between geographic mammography access and breast cancer-related outcomes. Future studies should focus on the development and application of more precise and consistent measures of geographic access to mammography.
Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Early Detection of Cancer; Female; Geographic Mapping; Health Services Accessibility; Humans; Mammography; Mass Screening; Middle Aged; Neoplasm Staging; Residence Characteristics; Time Factors
PubMed: 26219677
DOI: 10.1016/j.whi.2015.05.010 -
Annals of Oncology : Official Journal... Mar 2016Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and... (Meta-Analysis)
Meta-Analysis Review
Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients.
Topics: Antineoplastic Agents; Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Chemotherapy, Adjuvant; Clodronic Acid; Consensus; Diphosphonates; Europe; Female; Humans; Imidazoles; Neoplasm Recurrence, Local; Osteoporosis; Surveys and Questionnaires; Zoledronic Acid
PubMed: 26681681
DOI: 10.1093/annonc/mdv617 -
Cancer Management and Research 2019The evidence from recent epidemiological studies investigating the relationship between bone mineral density (BMD) and the risk of breast cancer (BC) remains...
PURPOSE
The evidence from recent epidemiological studies investigating the relationship between bone mineral density (BMD) and the risk of breast cancer (BC) remains inconsistent.
MATERIALS AND METHODS
The PubMed, EMBASE, and Web of Science databases were comprehensively searched by two independent authors to identify related cohort studies from the inception of the databases through January 31, 2018. Similarly, two researchers separately extracted the data from the selected studies, and any differences were resolved by discussion. Summarized relative risks (RRs) and 95% CIs were summarized via inverse variance weighted random-effects meta-analysis. Heterogeneity among studies was assessed with the statistic.
RESULTS
Ten studies with 1,522 BC patients among 81,902 participants were included in this meta-analysis. Compared to the participants with the lowest BMD at the lumbar spine, those with the highest BMD had a significantly lower RR for BC (RR =0.75; 95% CI =0.60-0.93; =23.0%). In the subgroup analyses, although the directions of the results were consistent with those of the main findings, not all showed statistical significance. We failed to detect an association between BMD at the femoral neck or total hip and the risk of BC (RR =0.94; 95% CI =0.66-1.33; =72.5%). Furthermore, the results of the dose-response analysis did not show a significant association between BMD at the lumbar spine, femoral neck, or total hip and the risk of BC. Funnel plot and statistical analyses showed no evidence of publication bias.
CONCLUSION
There is no relationship between BMD and the risk of BC. More prospective cohort studies are warranted to further investigate this issue.
PubMed: 30863156
DOI: 10.2147/CMAR.S188251 -
PloS One 2016The prognostic values of tumor-infiltrating lymphocytes (TILs) and TILs subsets in breast cancer (BC) are uncertain. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prognostic values of tumor-infiltrating lymphocytes (TILs) and TILs subsets in breast cancer (BC) are uncertain.
METHODS
A systematic literature search (MEDLINE, Web of Science, EMBASE, and the Cochrane Library to August 2014) was conducted for studies which met the eligibility criteria. The primary clinical outcome was defined as disease-free survival (DFS), overall survival (OS), and BC-specific survival (BCSS). Random or fixed-effects model was adopted to estimate the summary hazard ratio (HR).
RESULTS
Twenty-five published studies comprising 22,964 patients were reviewed. Pooled analysis indicated that TILs were not prognostic markers for DFS and OS in overall population, but related to improved DFS (HR, 0.82; 95% CI, 0.76-0.88) and OS (HR, 0.79; 95% CI, 0.71-0.87) in triple negative breast cancer (TNBC) patients. For TILs subsets, CD8+ lymphocytes were associated with improved DFS (HR, 0.69; 95% CI, 0.56-0.84) and BCSS (HR, 0.78; 95% CI, 0.71-0.86) in overall population, while FOXP3+ lymphocytes were associated with reduced DFS (HR, 1.47; 95% CI, 1.01-2.05) and OS (HR, 1.50; 95% CI, 1.15-1.97). In estrogen receptor (ER) negative patients, CD8+ lymphocytes was also related to better BCSS. In addition, the high density of CD20+, CD3+ or low level of PD-1+ or γδ T lymphocytes indicated increased OS in limited studies.
CONCLUSION
TILs and TILs subsets are promising prognostic biomarkers in breast cancer, especially in TNBC.
Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Lymphocytes, Tumor-Infiltrating; Prognosis
PubMed: 27073890
DOI: 10.1371/journal.pone.0152500 -
TheScientificWorldJournal 2014Breast density (BD) is recognized as one of the strongest independent risk factors of breast cancer (BC). Unlike most other risk factors, BD can be modified, suggesting... (Review)
Review
Breast density (BD) is recognized as one of the strongest independent risk factors of breast cancer (BC). Unlike most other risk factors, BD can be modified, suggesting that it may be a biomarker for preventive interventions. We conducted a qualitative systematic review to address the effect of preventive hormonal therapy on BD. Among the 26 relevant studies, 10 assessed the effect of tamoxifen on BD (TAM: n = 2,877), 9 that of raloxifene (RLX: n = 1,544), and 7 that of aromatase inhibitors (AI: n = 416). The studies were characterized by a large heterogeneity in designs and in methods of BD measurement. BD could be reduced by TAM (10 studies/10). However, the effect of RLX and AI on BD remains unclear due to conflicting results between studies. Consequently, it is crucial to develop practical, accurate, and reproducible methods of measurement in order to be able to compare the effect of preventive hormonal agents on BD and to determine whether change in BD can be used as a predictor of response to therapy.
Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Humans; Raloxifene Hydrochloride; Tamoxifen
PubMed: 24895676
DOI: 10.1155/2014/942386 -
Health Technology Assessment... Jul 2013Denosumab offers an alternative, or additional, treatment for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumours. (Review)
Review
BACKGROUND
Denosumab offers an alternative, or additional, treatment for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumours.
OBJECTIVES
The aim of this review was to assess the clinical effectiveness and cost-effectiveness of denosumab, within its licensed indication, for the prevention of SREs in patients with bone metastases from solid tumours.
DATA SOURCES
Databases searched were MEDLINE (1948 to April 2011), EMBASE (1980 to March 2011), The Cochrane Library (all sections; Issue 1, 2011) and Web of Science with Conference Proceedings (1970 to May 2011).
REVIEW METHODS
Only randomised controlled trials (RCTs) assessing denosumab, bisphosphonates (BPs) or best supportive care (BSC) in patients with bone metastases were included. Systematic reviews and observational studies were used for safety and quality-of-life assessments. Study quality was assessed using the Cochrane risk of bias tool. Studies suitable for meta-analysis were synthesised using network meta-analysis (NMA). A systematic review was conducted for cost, quality-of-life and cost-effectiveness studies. The results of this informed the cost-utility modelling. This principally estimated the cost-effectiveness of denosumab relative to zoledronic acid for when BPs are currently recommended and relative to BSC when BPs are not recommended or are contraindicated.
RESULTS
A literature search identified 39 studies (eight suitable for NMA). Denosumab was effective in delaying time to first SRE and reducing the risk of multiple SREs compared with zoledronic acid. Generally speaking, denosumab was similar to zoledronic acid for quality of life, pain, overall survival and safety. The NMA demonstrated that denosumab was more effective in delaying SREs than placebo, but was limited by numerous uncertainties. Cost-utility modelling results for denosumab relative to zoledronic acid were driven by the availability of the patient access scheme (PAS) for denosumab. Without this, denosumab was not estimated to be cost-effective compared with zoledronic acid. With it, the cost-effectiveness ranged between dominance for breast and prostate cancer, to between £5400 and £15,300 per quality-adjusted life-year (QALY) for other solid tumours (OSTs) including non-small cell lung cancer (NSCLC) and £12,700 per QALY for NSCLC. Owing to small patient gains estimated, the cost-effectiveness of denosumab was very sensitive to the zoledronic acid price. Denosumab was not estimated to be cost-effective compared with BSC.
LIMITATIONS
Only subgroup data were available for denosumab for NSCLC, and OSTs excluding NSCLC. The NMA was subject to numerous uncertainties. Owing to small patient gains estimated, the cost-effectiveness of denosumab was very sensitive to the zoledronic acid price.
CONCLUSION
Denosumab, compared with zoledronic acid and placebo, is effective in delaying SREs, but is similar with regard to quality of life and pain. Cost-effectiveness showed that without the PAS denosumab was not estimated to be cost-effective relative to either zoledronic acid or BSC. With the PAS, denosumab was estimated to be cost-effective relative to zoledronic acid but not BSC.
STUDY REGISTRATION
PROSPERO number CRD42011001418.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Antibodies, Monoclonal, Humanized; Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Cost-Benefit Analysis; Denosumab; Female; Humans; Lung Neoplasms; Male; Models, Economic; Prostatic Neoplasms; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic
PubMed: 23870108
DOI: 10.3310/hta17290