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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

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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

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Review published: .

CRD summary

This updated review assessed the benefits and harms of risk assessment, genetic counselling and genetic testing for BRCA-related cancer in women. The authors concluded that potential benefits and harms of risk assessment, genetic counselling, genetic testing and interventions to reduce cancer and mortality varied with risk. The conclusion and specific findings of the review are probably reliable.

Authors' objectives

To review new evidence on the benefits and harms of risk assessment, genetic counselling and genetic testing for BRCA-related cancer in women. This updates a previous review (see Other Publications of Related Interest below).

Searching

MEDLINE, PsycINFO, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL) and the Health Technology Assessment (HTA) Database were searched from 2004 to dates up to July 2013. Reference lists were checked and citations of key studies were reviewed using Scopus. Studies from the earlier review were also assessed for inclusion. Only studies reported in English were eligible for inclusion.

Study selection

The target population for assessment of risk models, counselling or screening was women without known cancer or BRCA mutations in clinical settings relevant to US primary care practice. For interventions designed to reduce risk, the target population was women with known mutations. Randomised controlled trials (RCTs), systematic reviews, cohort studies, case control studies and diagnostic accuracy studies were eligible for inclusion if they assessed accuracy of risk assessment methods, outcomes of genetic counselling and testing or effectiveness of interventions to reduce BRCA-related cancer and mortality in women who are carriers of the BRCA1 or BRCA2 genes. Risk assessment methods were included in the review if designed to guide referrals to genetic specialists and usable by non-specialists in primary care practice. Eligible interventions were intensive screening, risk-reducing medications approved by the U.S. Food and Drug Administration and risk-reducing surgery. Studies of any design that assessed potential adverse effects of interventions in women at high risk of BRCA-related cancer were eligible for inclusion.

Study characteristics varied widely and depended on the specific intervention assessed. Full details were reported in an online appendix.

The authors did not report how many reviewers selected studies for review.

Assessment of study quality

Two reviewers assessed studies using the criteria of the United States Preventative Services Task Force. They then rated studies as good, fair or poor quality. Disagreements were resolved through discussion. Descriptive, cross-sectional studies, pre-post studies and case series were not formally assessed.

Data extraction

One reviewer extracted data on all aspects of the studies, including key outcomes, and this was checked by a second reviewer.

Methods of synthesis

The studies were combined in a narrative synthesis structured by the intervention assessed and the outcome reported. Studies were considered consistent if outcomes were generally in the same direction of effect and ranges of effect sizes were narrow.

Results of the review

Referral models (ten studies, five referral models were identified): Sensitivity and specificity varied depending on the population in which the models were assessed. Estimates were high (sensitivity between 87 and 100%) in studies conducted in primary care screening populations. Populations with higher prevalence of BRCA carriers showed lower sensitivity.

Genetic counselling (27 studies): Several studies reported decreased intentions to participate, or actual participation in screening following genetic counselling. Breast cancer-related worry either decreased or did not change following counselling; no studies reported increases. Where reported, measures of anxiety and depression also generally decreased or did not differ following counselling.

Genetic Testing, adverse effects (13 studies): Five studies reported significantly increased breast cancer-related worry after receipt of BRCA results. These increases were confined to mutation carriers. One study reported a decrease in breast cancer-related worry for both carriers and non-carriers. Studies reported mixed results for anxiety; some found decreases regardless of carrier status whilst others reported decreases for non-carriers and increases for carriers. Depression scores also showed varying impacts.

Risk-reducing interventions

Intensive screening (five studies): There were no studies of the effectiveness of intensive screening; five studies of intensive breast cancer screening of mutation carriers and other high-risk women reported adverse effects. These included mixed evidence but some studies showed more false positives with MRI than mammography but some indication of fewer false negatives. Recall rates for MRI were also higher in one study, mostly for benign findings. Additional unnecessary imaging procedures and biopsies were also higher in patients who had had MRI in one study. Discomfort, pain and anxiety were not generally increased by intensive yearly screening compared to usual surveillance. One study assessed ovarian cancer screening and found high levels of unnecessary diagnostic surgery (55%); 3% of screening visits detected some abnormality of which around one fifth were cancerous.

Medications (three studies): There were no trials that evaluated the efficacy of risk-reducing medications in mutation carriers. Three trials in women at various risk levels showed reduced risks for oestrogen receptor positive cancer in those treated with prophylactic tamoxifen or raloxifene. Higher rates of several categories of adverse events were reported in women in these active treatment groups, including thromboembolic events and endometrial events including cancer.

Surgery (six studies): Three studies reported the impact of bilateral mastectomies. Two found a reduced incidence of breast cancer occurred in the intervention group compared with non-operated carriers. Surgical complications were frequent. Another reported less anxiety in women after surgery but no change on other psychological measures. One study of salpingo-oophorectomy and one of oophorectomy reported reduced incidences of ovarian cancer or breast cancer (one study each). Two other small studies described some adverse effects of oophorectomy.

Authors' conclusions

The potential benefits and harms of risk assessment, genetic counselling, genetic testing and interventions to reduce cancer and mortality varied with risk.

CRD commentary

The review questions were clear, although broad, and were supported by clear inclusion criteria. The search was reasonable, but language restrictions may have increased the chance that some relevant studies were not included. The quality of included studies was assessed using appropriate criteria. Methods to reduce the chances of mistakes or biases by researchers were reported for this assessment and for the data extraction; it was not clear if they were also used for the inclusion of studies.. The synthesis appeared balanced and appropriate.

This was a generally well-conducted review of a wide range of interventions and its findings appear likely to be reliable.

Implications of the review for practice and research

Practice: The authors stated that services should be well-integrated and highly personalised in order to maximise benefits and minimise harms for women and their families.

Research: The authors identified extensive implications for research. These included the need for research on access to testing, effectiveness of screening approaches including risk stratification; use of system supports and patient acceptance and education. They also recommended an expanded database of women receiving genetic counselling and and testing for BRCA and research on the consequences of identifying women as high risk. Finally they made specific recommendations for the further assessment of interventions to reduce risk.

Funding

Agency for Healthcare Research and Quality.

Bibliographic details

Nelson HD, Pappas M, Zakher B, Mitchell JP, Okinaka-Hu L, Fu R. 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 Annals of Internal Medicine 2014; 160(4): 255-266. [PubMed: 24366442]

Other publications of related interest

US Preventative Services Task Force. Generic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: recommendations statement. Annals of Internal Medicine. 2005; 143: 355-361.

Indexing Status

Subject indexing assigned by CRD

MeSH

Breast Neoplasms; Humans; Genetic Testing; Genes, BRCA1; Genes, BRCA2; Mutation; Ovarian Neoplasms; Risk Assessment; Counseling

AccessionNumber

12014003528

Database entry date

17/01/2014

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

Copyright © 2014 University of York.
Bookshelf ID: NBK179374

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