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The Cochrane Database of Systematic... Apr 2018Recent progress in understanding the genetic basis of breast cancer and widely publicized reports of celebrities undergoing risk-reducing mastectomy (RRM) have increased... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent progress in understanding the genetic basis of breast cancer and widely publicized reports of celebrities undergoing risk-reducing mastectomy (RRM) have increased interest in RRM as a method of preventing breast cancer. This is an update of a Cochrane Review first published in 2004 and previously updated in 2006 and 2010.
OBJECTIVES
(i) To determine whether risk-reducing mastectomy reduces death rates from any cause in women who have never had breast cancer and in women who have a history of breast cancer in one breast, and (ii) to examine the effect of risk-reducing mastectomy on other endpoints, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes.
SEARCH METHODS
For this Review update, we searched Cochrane Breast Cancer's Specialized Register, MEDLINE, Embase and the WHO International Clinical Trials Registry Platform (ICTRP) on 9 July 2016. We included studies in English.
SELECTION CRITERIA
Participants included women at risk for breast cancer in at least one breast. Interventions included all types of mastectomy performed for the purpose of preventing breast cancer.
DATA COLLECTION AND ANALYSIS
At least two review authors independently abstracted data from each report. We summarized data descriptively; quantitative meta-analysis was not feasible due to heterogeneity of study designs and insufficient reporting. We analyzed data separately for bilateral risk-reducing mastectomy (BRRM) and contralateral risk-reducing mastectomy (CRRM). Four review authors assessed the methodological quality to determine whether or not the methods used sufficiently minimized selection bias, performance bias, detection bias, and attrition bias.
MAIN RESULTS
All 61 included studies were observational studies with some methodological limitations; randomized trials were absent. The studies presented data on 15,077 women with a wide range of risk factors for breast cancer, who underwent RRM.Twenty-one BRRM studies looking at the incidence of breast cancer or disease-specific mortality, or both, reported reductions after BRRM, particularly for those women with BRCA1/2 mutations. Twenty-six CRRM studies consistently reported reductions in incidence of contralateral breast cancer but were inconsistent about improvements in disease-specific survival. Seven studies attempted to control for multiple differences between intervention groups and showed no overall survival advantage for CRRM. Another study showed significantly improved survival following CRRM, but after adjusting for bilateral risk-reducing salpingo-oophorectomy (BRRSO), the CRRM effect on all-cause mortality was no longer significant.Twenty studies assessed psychosocial measures; most reported high levels of satisfaction with the decision to have RRM but greater variation in satisfaction with cosmetic results. Worry over breast cancer was significantly reduced after BRRM when compared both to baseline worry levels and to the groups who opted for surveillance rather than BRRM, but there was diminished satisfaction with body image and sexual feelings.Seventeen case series reporting on adverse events from RRM with or without reconstruction reported rates of unanticipated reoperations from 4% in those without reconstruction to 64% in participants with reconstruction.In women who have had cancer in one breast, removing the other breast may reduce the incidence of cancer in that other breast, but there is insufficient evidence that this improves survival because of the continuing risk of recurrence or metastases from the original cancer. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention, when considering RRM.
AUTHORS' CONCLUSIONS
While published observational studies demonstrated that BRRM was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies are suggested. BRRM should be considered only among those at high risk of disease, for example, BRCA1/2 carriers. CRRM was shown to reduce the incidence of contralateral breast cancer, but there is insufficient evidence that CRRM improves survival, and studies that control for multiple confounding variables are recommended. It is possible that selection bias in terms of healthier, younger women being recommended for or choosing CRRM produces better overall survival numbers for CRRM. Given the number of women who may be over-treated with BRRM/CRRM, it is critical that women and clinicians understand the true risk for each individual woman before considering surgery. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention when considering RRM.
Topics: Breast Neoplasms; Female; Genes, BRCA1; Genes, BRCA2; Genetic Predisposition to Disease; Humans; Observational Studies as Topic; Patient Satisfaction; Postoperative Complications; Prophylactic Mastectomy; Risk Assessment; Unilateral Breast Neoplasms
PubMed: 29620792
DOI: 10.1002/14651858.CD002748.pub4 -
Genetics in Medicine : Official Journal... Oct 2018To review the evidence for the effectiveness and cost-effectiveness of cancer risk management interventions for BRCA carriers.
PURPOSE
To review the evidence for the effectiveness and cost-effectiveness of cancer risk management interventions for BRCA carriers.
METHODS
Comparative effectiveness and cost-effectiveness analyses were identified by searching scientific and health economic databases. Eligible studies modeled the impact of a cancer risk management intervention in BRCA carriers on life expectancy (LE), cancer incidence, or quality-adjusted life years (QALYs), with or without costs.
RESULTS
Twenty-six economic evaluations and eight comparative effectiveness analyses were included. Combined risk-reducing salpingo-oophorectomy and prophylactic mastectomy resulted in the greatest LE and was cost-effective in most analyses. Despite leading to increased LE and QALYs, combined mammography and breast magnetic resonance imaging (MRI) was less likely to be cost-effective than either mammography or MRI alone, particularly for women over 50 and BRCA2 carriers. Variation in patient compliance to risk management interventions was incorporated in 11/34 studies with the remaining analyses assuming 100% adherence.
CONCLUSION
Prophylactic surgery and intensive breast screening are effective and cost-effective in models of BRCA carrier risk management. Findings were based predominantly on assuming perfect adherence to recommendations without assessment of the health-care resource use and costs related to engaging patients and maximizing compliance, meaning the real-world impact on clinical outcomes and resource use remains unclear.
Topics: BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Cost-Benefit Analysis; Female; Humans; Mass Screening; Risk Management
PubMed: 29323669
DOI: 10.1038/gim.2017.255 -
BMC Women's Health Mar 2017It is unclear if the use of hormone therapy (HT) in carriers of BRCA mutations improves the quality of life (QOL) without increasing the risk of breast cancer following... (Review)
Review
BACKGROUND
It is unclear if the use of hormone therapy (HT) in carriers of BRCA mutations improves the quality of life (QOL) without increasing the risk of breast cancer following a risk-reducing salpingo-oophorectomy (RRSO). Our objective was to assess the effect of HT on QOL and breast cancer risk, after RRSO.
METHODS
We searched MEDLINE, EMBASE, CINHAL, and others, from inception to July 22, 2016, to identify relevant studies. Two reviewers independently screened identified records for controlled trials and observational studies that addressed the effect of HT on QOL and breast cancer risk in women with BRCA mutations, post RRSO. Two reviewers independently extracted data on populations, interventions, comparators, outcomes, and methodological quality. Studies addressing the same outcome were synthesized using written evidence summaries or tables.
RESULTS
Of the 1,059 records identified, 13 met our inclusion criteria. All studies were observational. Six studies assessed the effect on QOL. Of these, 3 showed improvement in QOL with HT use. The risk of breast cancer was evaluated in 4 studies. The mean duration of follow-up was 2.6 years (range 0.1-19.1). The risk of breast cancer did not change with HT use in all 4 studies.
CONCLUSIONS
Cumulative evidence from our review suggests that short-term HT use following RRSO improves QOL. The effect on breast cancer risk is still unclear. There are too few long-term studies to draw any strong conclusions. The need for future well-designed RCTs for more established evidence is imperative.
Topics: Breast Neoplasms; Female; Genes, BRCA1; Hormone Replacement Therapy; Humans; Ovariectomy; Quality of Life; Risk Reduction Behavior; Salpingectomy
PubMed: 28320467
DOI: 10.1186/s12905-017-0370-6 -
The Oncologist Apr 2017The objective of this study was to review the role of bilateral salpingo-oophorectomy in mutation (m) carriers and alternative interventions in risk reduction of... (Review)
Review
OBJECTIVE
The objective of this study was to review the role of bilateral salpingo-oophorectomy in mutation (m) carriers and alternative interventions in risk reduction of ovarian cancer (OC).
MATERIALS AND METHODS
A systematic review using PubMed, MEDLINE, EMBASE, and the Cochrane library was conducted to identify studies of different strategies to prevent OC in m carriers, including bilateral salpingo-oophorectomy, prophylactic salpingectomy with delayed oophorectomy, intensive surveillance, and chemoprevention.
RESULTS
Risk-reducing bilateral salpingo-oophorectomy is an effective intervention, but its associated morbidity is substantial and seems to curtail uptake rates among the target population. Although there is much interest and a strong theoretical basis for salpingectomy with delayed oophorectomy, data on its clinical application are scarce with regard to screening, the use of an algorithmic protocol has recently shown favorable albeit indefinite results in average-risk postmenopausal women. Its incorporation into studies focused on high-risk women might help solidify a future role for screening as a bridge to surgery. The use of oral contraceptives for chemoprevention is well supported by epidemiologic studies. However, there is a lack of evidence for advocating any of the other agents proposed for this purpose, including nonsteroidal anti-inflammatory drugs, vitamin D, and retinoids.
CONCLUSION
Further studies are needed before salpingectomy with delayed oophorectomy or intensive surveillance can be offered as acceptable, less morbid alternatives to upfront oophorectomy for m carriers. 2017;22:450-459 IMPLICATIONS FOR PRACTICE: Risk-reducing bilateral salpingo-oophorectomy is currently the most effective method for reducing the risk of ovarian cancer in mutation (m) carriers. Unfortunately, it is associated with significant short- and long-term morbidity, stemming from reduced circulating estrogen. In recent years, much research has been devoted to evaluating less morbid alternatives, especially multimodal cancer screening and prophylactic salpingectomy with delayed oophorectomy. This review describes the present state of the art, with the aim of informing the counseling provided to m carriers on this complicated issue and encouraging additional research to facilitate the incorporation of such alternatives into routine practice.
Topics: BRCA1 Protein; BRCA2 Protein; Female; Heterozygote; Humans; Mutation; Ovarian Neoplasms; Risk Factors; Salpingo-oophorectomy
PubMed: 28314837
DOI: 10.1634/theoncologist.2016-0444 -
Journal of Ovarian Research Aug 2016The aims of this report were to describe a case of ovarian adenosquamous carcinoma and to systematically review the pertinent literature. (Review)
Review
BACKGROUND
The aims of this report were to describe a case of ovarian adenosquamous carcinoma and to systematically review the pertinent literature.
METHODS
We describe a case in which a 57-year-old woman had stage IC ovarian cancer histologically diagnosed as adenosquamous carcinoma. We also systematically reviewed the literature using the PubMed database.
CASE PRESENTATION
Preoperative computed tomography and magnetic resonance imaging showed a tumor measuring 14 cm in diameter and containing solid areas. Tumor marker levels were as follows: CA125, 42.6 U/mL; CA 19-9, 134.1 U/mL; CEA, 0.9 ng/mL; and SCC, 1.6 ng/mL. The patient underwent multiple surgeries including total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node dissection, para-aortic lymph node biopsy, and total omentectomy. Based on the cytological features of the ascitic fluid, the tumor was diagnosed as a squamous cell carcinoma. Histological examination of an excised specimen showed the transition of an endometrioid adenocarcinoma to a squamous cell carcinoma. There was no evidence of any teratomas or endometriosis-related features. We considered the tumor to be an adenosquamous carcinoma, with the squamous cell carcinoma component arising from the endometrioid adenocarcinoma component. After surgery, the patient underwent 6 cycles of paclitaxel and carboplatin chemotherapy. There has been no recurrence to date, 66 months after the initial treatment.
RESULTS
Histologically, the 8 adenosquamous carcinomas reported in the literature either arose from the mature cystic teratoma (4 cases) or endometriosis (3 cases) or were pure adenosquamous carcinomas (1 case). Our literature search uncovered no cases of ovarian adenosquamous carcinomas originating from endometrioid adenocarcinomas.
CONCLUSIONS
This is the first reported case of an adenosquamous carcinoma arising from an endometrioid adenocarcinoma. Because such tumors are rare, their standard management is unclear.
Topics: Adult; Carboplatin; Carcinoma, Adenosquamous; Carcinoma, Endometrioid; Carcinoma, Squamous Cell; Female; Gynecologic Surgical Procedures; Humans; Middle Aged; Ovarian Neoplasms; Paclitaxel; Survival Analysis
PubMed: 27514842
DOI: 10.1186/s13048-016-0255-6 -
Obstetrics and Gynecology Sep 2016To compare the long-term risks associated with salpingo-oophorectomy with ovarian conservation at the time of benign hysterectomy. (Review)
Review
OBJECTIVE
To compare the long-term risks associated with salpingo-oophorectomy with ovarian conservation at the time of benign hysterectomy.
DATA SOURCES
MEDLINE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials were searched from inception to January 30, 2015. We included prospective and retrospective comparative studies of women with benign hysterectomy who had either bilateral salpingo-oophorectomy (BSO) or conservation of one or both ovaries.
METHODS OF STUDY SELECTION
Reviewers double-screened 5,568 citations and extracted eligible studies into customized forms. Twenty-six comparative studies met inclusion criteria. Studies were assessed for results, quality, and strength of evidence.
TABULATION, INTEGRATION, AND RESULTS
Studies were extracted for participant, intervention, comparator, and outcomes data. When compared with hysterectomy with BSO, prevalence of reoperation and ovarian cancer was higher in women with ovarian conservation (ovarian cancer risk of 0.14-0.7% compared with 0.02-0.04% among those with BSO). Hysterectomy with BSO was associated with a lower incidence of breast and total cancer, but no difference in the incidence of cancer mortality was found when compared with ovarian conservation. All-cause mortality was higher in women younger than age 45 years at the time of BSO who were not treated with estrogen replacement therapy (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.04-1.92). Coronary heart disease (HR 1.26, 95% CI 1.04-1.54) and cardiovascular death were higher among women with BSO (HR 1.84, 95% CI 1.27-2.68), especially women younger than 45 years who were not treated with estrogen. Finally, there was an increase in the prevalence of dementia and Parkinson disease among women with BSO compared with conservation, especially in women younger than age 50 years. Clinical practice guidelines were devised based on these results.
CONCLUSION
Bilateral salpingo-oophorectomy offers the advantage of effectively eliminating the risk of ovarian cancer and reoperation but can be detrimental to other aspects of health, especially among women younger than age 45 years.
Topics: Age Factors; Female; Humans; Hysterectomy; Organ Sparing Treatments; Outcome and Process Assessment, Health Care; Ovarian Neoplasms; Ovariectomy; Patient Selection; Risk Assessment; Salpingectomy
PubMed: 27500347
DOI: 10.1097/AOG.0000000000001592 -
Health Technology Assessment... Sep 2014Lynch syndrome (LS) is an inherited autosomal dominant disorder characterised by an increased risk of colorectal cancer (CRC) and other cancers, and caused by mutations... (Review)
Review
BACKGROUND
Lynch syndrome (LS) is an inherited autosomal dominant disorder characterised by an increased risk of colorectal cancer (CRC) and other cancers, and caused by mutations in the deoxyribonucleic acid (DNA) mismatch repair genes.
OBJECTIVE
To evaluate the accuracy and cost-effectiveness of strategies to identify LS in newly diagnosed early-onset CRC patients (aged < 50 years). Cascade testing of relatives is employed in all strategies for individuals in whom LS is identified.
DATA SOURCES AND METHODS
Systematic reviews were conducted of the test accuracy of microsatellite instability (MSI) testing or immunohistochemistry (IHC) in individuals with CRC at risk of LS, and of economic evidence relating to diagnostic strategies for LS. Reviews were carried out in April 2012 (test accuracy); and in February 2012, repeated in February 2013 (economic evaluations). Databases searched included MEDLINE (1946 to April week 3, 2012), EMBASE (1980 to week 17, 2012) and Web of Science (inception to 30 April 2012), and risk of bias for test accuracy was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) quality appraisal tool. A de novo economic model of diagnostic strategies for LS was developed.
RESULTS
Inconsistencies in study designs precluded pooling of diagnostic test accuracy results from a previous systematic review and nine subsequent primary studies. These were of mixed quality, with significant methodological concerns identified for most. IHC and MSI can both play a part in diagnosing LS but neither is gold standard. No UK studies evaluated the cost-effectiveness of diagnosing and managing LS, although studies from other countries generally found some strategies to be cost-effective compared with no testing. The de novo model demonstrated that all strategies were cost-effective compared with no testing at a threshold of £20,000 per quality-adjusted life-year (QALY), with the most cost-effective strategy utilising MSI and BRAF testing [incremental cost-effectiveness ratio (ICER) = £5491 per QALY]. The maximum health benefit to the population of interest would be obtained using universal germline testing, but this would not be a cost-effective use of NHS resources compared with the next best strategy. When the age limit was raised from 50 to 60 and 70 years, the ICERs compared with no testing increased but remained below £20,000 per QALY (except for universal germline testing with an age limit of 70 years). The total net health benefit increased with the age limit as more individuals with LS were identified. Uncertainty was evaluated through univariate sensitivity analyses, which suggested that the parameters substantially affecting cost-effectiveness: were the risk of CRC for individuals with LS; the average number of relatives identified per index patient; the effectiveness of colonoscopy in preventing metachronous CRC; the cost of colonoscopy; the duration of the psychological impact of genetic testing on health-related quality of life (HRQoL); and the impact of prophylactic hysterectomy and bilateral salpingo-oophorectomy on HRQoL (this had the potential to make all testing strategies more expensive and less effective than no testing).
LIMITATIONS
The absence of high-quality data for the impact of prophylactic gynaecological surgery and the psychological impact of genetic testing on HRQoL is an acknowledged limitation.
CONCLUSIONS
Results suggest that reflex testing for LS in newly diagnosed CRC patients aged < 50 years is cost-effective. Such testing may also be cost-effective in newly diagnosed CRC patients aged < 60 or < 70 years. Results are subject to uncertainty due to a number of parameters, for some of which good estimates were not identified. We recommend future research to estimate the cost-effectiveness of testing for LS in individuals with newly diagnosed endometrial or ovarian cancer, and the inclusion of aspirin chemoprevention. Further research is required to accurately estimate the impact of interventions on HRQoL.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42012002436.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Aged; Colorectal Neoplasms, Hereditary Nonpolyposis; Cost-Benefit Analysis; Genetic Testing; Humans; Middle Aged
PubMed: 25244061
DOI: 10.3310/hta18580 -
Annals of Internal Medicine Feb 2014Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer. (Review)
Review
Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the U.S. Preventive Services Task Force recommendation.
BACKGROUND
Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer.
PURPOSE
To review new evidence on the benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women.
DATA SOURCES
MEDLINE and PsycINFO between 2004 and 30 July 2013, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews from 2004 through the second quarter of 2013, Health Technology Assessment during the fourth quarter of 2012, Scopus, and reference lists.
STUDY SELECTION
English-language studies about accuracy of risk assessment and benefits and harms of genetic counseling, genetic testing, and interventions to reduce cancer incidence and mortality.
DATA EXTRACTION
Individual investigators extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability by using established criteria.
DATA SYNTHESIS
Five referral models accurately estimated individual risk for BRCA mutations. Genetic counseling increased the accuracy of risk perception and decreases the intention for genetic testing among unlikely carriers and cancer-related worry, anxiety, and depression. No trials evaluated the effectiveness of intensive screening or risk-reducing medications in mutation carriers, although false-positive rates, unneeded imaging, and unneeded surgeries were higher with screening. Among high-risk women and mutation carriers, risk-reducing mastectomy decreased breast cancer by 85% to 100% and breast cancer mortality by 81% to 100% compared with women without surgery; risk-reducing salpingo-oophorectomy decreased breast cancer incidence by 37% to 100%, ovarian cancer by 69% to 100%, and all-cause mortality by 55% to 100%.
LIMITATION
The analysis included only English-language articles;efficacy trials in mutation carriers were lacking.
CONCLUSION
Studies of risk assessment, genetic counseling, genetic testing, and interventions to reduce cancer and mortality indicate potential benefits and harms that vary according to risk.
Topics: Anxiety; Breast Neoplasms; Depression; Fallopian Tube Neoplasms; Female; Genes, BRCA1; Genes, BRCA2; Genetic Counseling; Genetic Predisposition to Disease; Genetic Testing; Humans; Mutation; Ovarian Neoplasms; Risk Assessment
PubMed: 24366442
DOI: 10.7326/M13-1684 -
The Cochrane Database of Systematic... Jan 2013The surgical management of ovarian tumors in pregnancy is similar to that of non-pregnant women. The procedures include resection of the tumor (enucleation), removal of... (Review)
Review
BACKGROUND
The surgical management of ovarian tumors in pregnancy is similar to that of non-pregnant women. The procedures include resection of the tumor (enucleation), removal of an ovary or ovaries (oophorectomy), or surgical excision of the fallopian tube and ovary (salpingo-oophorectomy). The procedure can be done by open surgery (laparotomy) or keyhole surgery (laparoscopy) technique. The benefits of laparoscopic surgery include shorter hospital stay, earlier return to normal activity, and reduced postoperative pain. However, conventional laparoscopic surgery techniques required the infusion of gas carbon dioxide in the peritoneum to distend the abdomen and displace the bowel upward to create the room for surgical manipulation. Serious complications such as abnormally high levels of carbon dioxide in the circulating blood (hypercarbia) and perforation of internal organs have also been reported. These serious complication may be harmful to the fetus.
OBJECTIVES
To compare the effects of using laparoscopic surgery for benign ovarian tumor during pregnancy on maternal and fetal health and the use of healthcare resources.
SEARCH METHODS
We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 11 November 2012.
SELECTION CRITERIA
Randomized controlled trials with reported data that compared outcomes of laparoscopic surgery for benign ovarian tumor in pregnancy to conventional laparotomy technique.
DATA COLLECTION AND ANALYSIS
Two review authors planned to independently assess trial quality and extract data.
MAIN RESULTS
The updated search did not identify any randomized controlled trials.
AUTHORS' CONCLUSIONS
The practice of laparoscopic surgery for benign ovarian tumour during pregnancy is associated with benefits and harms. However, the evidence for the magnitude of these benefits and harms is drawn from case series studies, associated with potential bias. The results and conclusions of these studies must therefore be interpreted with caution.The available case series studies of laparoscopic surgery for benign ovarian tumour during pregnancy provide limited insight into the potential benefits and harms associated with this new surgical technique in pregnancy. Randomized controlled trials are required to provide the most reliable evidence regarding the benefits and harms of laparoscopic surgery for benign ovarian tumour during pregnancy.
Topics: Female; Humans; Laparoscopy; Ovarian Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic
PubMed: 23440802
DOI: 10.1002/14651858.CD005459.pub3