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Cancer Epidemiology, Biomarkers &... Dec 2004Women who are carriers of BRCA gene mutations have an elevated lifetime risk of developing breast or ovarian cancer. Although a number of risk-reducing options are... (Review)
Review
OBJECTIVE
Women who are carriers of BRCA gene mutations have an elevated lifetime risk of developing breast or ovarian cancer. Although a number of risk-reducing options are currently available to mutation carriers, uncertainty exists in terms of their efficacy. A systematic review of the literature was conducted to describe the utilization of screening and preventive surgery among unaffected mutation carriers in the face of uncertainty.
METHODS
MEDLINE, PubMed, and CANCERLIT, English-only computerized literature searches were done to identify articles pertaining to decisions made by unaffected BRCA mutation carriers to reduce risk of breast and ovarian cancer. Studies were required to include information on choices taken by at-risk women following disclosure of a positive BRCA test.
RESULTS
Only seven studies (5 American and 2 Dutch studies) were identified. The proportion of mutation carriers who chose preventive surgery over screening varied widely across the studies, ranging from 0% to 54% for prophylactic mastectomy and from 13% to 53% for prophylactic oophorectomy. Furthermore, a significant minority of women who chose surveillance failed to comply with the recommended schedule.
CONCLUSION
There is considerable variability within and between countries in risk reduction strategies utilized by healthy mutation carriers. This variability may relate to differences in (1) population characteristics; (2) recommendations for follow-up care of unaffected carriers; (3) prevailing values towards body integrity, femininity, and preventive surgery; and (4) health care funding systems. Future research needs to provide further insight into factors influencing women's decisions to adopt various risk reduction strategies.
Topics: Breast Neoplasms; DNA Mutational Analysis; Decision Making; Female; Genes, BRCA1; Genes, BRCA2; Genetic Predisposition to Disease; Genetic Testing; Humans; Ovarian Neoplasms; Ovariectomy; Patient Compliance; Risk Factors
PubMed: 15598752
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2004Breast cancer is the most common cancer and the second most common cause of cancer-related death among North American and Western European women. Recent progress in... (Review)
Review
BACKGROUND
Breast cancer is the most common cancer and the second most common cause of cancer-related death among North American and Western European women. Recent progress in understanding the genetic basis of breast cancer, along with rising incidence rates, have resulted in increased interest in prophylactic mastectomy as a method of preventing breast cancer, particularly in those with familial susceptibility.
OBJECTIVES
The primary objective was to determine whether prophylactic mastectomy reduces death from any cause in women who have never had breast cancer and in women who have a history of breast cancer in one breast. The secondary objective was to examine the effect of prophylactic mastectomy on other endpoints including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes.
SEARCH STRATEGY
Electronic searches were performed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cancerlit, and the Science Citation Index.
SELECTION CRITERIA
Inclusion criteria were studies in English of any design type including randomized or nonrandomized controlled trials, cohort studies, case-control studies, and case series with at least ten participants. 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, including subcutaneous mastectomy, total or simple mastectomy, modified radical mastectomy, and radical mastectomy.
DATA COLLECTION AND ANALYSIS
Information on patients, interventions, methods, and results were extracted by at least two independent reviewers. Methodological quality was assessed based on how well each study minimized potential selection bias, performance bias, detection bias, and attrition bias. Data for each study were summarized descriptively; quantitative meta-analysis was not feasible due to heterogeneity of study designs and insufficient reporting. Data were analyzed separately for bilateral prophylactic mastectomy (BPM) and contralateral prophylactic mastectomy (CPM).
MAIN RESULTS
Twenty-three studies, including more than 4,000 patients, met inclusion criteria. No randomized or nonrandomized controlled trials were found. Most studies were either case series or cohort studies. All studies had methodological limitations, with the most common source of potential bias being systematic differences between the intervention and comparison groups that could potentially be associated with a particular outcome. Thirteen studies assessed the effectiveness of BPM. No study assessed all-cause mortality after BPM. All studies reporting on incidence of breast cancer and disease-specific mortality reported reductions after BPM. Nine studies assessed psychosocial measures; most reported high levels of satisfaction with the decision to have prophylactic mastectomy (PM) but more variable satisfaction with cosmetic results. Only one study assessed satisfaction with the psychological support provided by healthcare personnel during risk counseling and showed that more women were dissatisfied than satisfied with the support they received in the healthcare setting. Worry over breast cancer was significantly reduced after BPM when compared both to baseline worry levels and to the groups who opted for surveillance rather than BPM. Three studies reported body image/feelings of femininity outcomes, and all reported that a substantial minority (about 20%) reported BPM had adverse effects on those domains. Six studies assessed contralateral prophylactic mastectomy. Studies consistently reported reductions in contralateral incidence of breast cancer but were inconsistent about improvements in disease-specific survival. Only one study attempted to control for multiple differences between intervention groups, and this study showed no overall survival advantage for CPM at 15 years. Two case series were exclusively focused on adverse events from prophylactic mastectomy with reconstruction, and both reported rates of unanticipated re-operations from 30% to 49%.
REVIEWERS' CONCLUSIONS
While published observational studies demonstrated that BPM was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies (ideally randomized trials) are needed. The studies need to be of sufficient duration and make better attempts to control for selection biases to arrive at better estimates of risk reduction. The state of the science is far from exact in predicting who will get or who will die from breast cancer. By one estimate, most of the women deemed high risk by family history (but not necessarily BRCA 1 or 2 mutation carriers) who underwent these procedures would not have died from breast cancer, even without prophylactic surgery. Therefore, women need to understand that this procedure should be considered only among those at very high risk of the disease. For women who had already been diagnosed with a primary tumor, the data were particularly lacking for indications for contralateral prophylactic mastectomy. While it appeared that contralateral mastectomy may reduce the incidence of cancer in the contralateral breast, there was insufficient evidence about whether, and for whom, CPM actually improved survival. Physical morbidity is not uncommon following PM, and many women underwent unanticipated re-operations (usually due to problems with reconstruction); however, these data need to be updated to reflect changes in surgical procedures and reconstruction. Regarding psychosocial outcomes, women generally reported satisfaction with their decisions to have PM but reported satisfaction less consistently for cosmetic outcomes, with diminished satisfaction often due to surgical complications. Therefore, physical morbidity and post-operative surgical complications were areas that should be considered when deciding about PM. With regard to emotional well-being, most women recovered well postoperatively, reporting reduced cancer worry and showing reduced psychological morbidity from their baseline measures; exceptions also have been noted. Of the psychosocial outcomes measured, body image and feelings of femininity were the most adversely affected.
Topics: Breast Neoplasms; Female; Genetic Predisposition to Disease; Humans; Mastectomy; Patient Satisfaction
PubMed: 15495033
DOI: 10.1002/14651858.CD002748.pub2