Association of Women Surgeons
Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers, a systematic review

https://doi.org/10.1016/j.amjsurg.2016.06.010Get rights and content

Abstract

Background

Mutations in BRCA1 or BRCA2 genes results in an elevated risk for developing both breast and ovarian cancers over the lifetime of affected carriers. General surgeons may be faced with questions about surgical risk reduction and survival benefit of prophylactic surgery.

Methods

A systematic literature review was performed using the electronic databases PubMed, OVID MEDLINE, and Scopus comparing prophylactic surgery vs observation with respect to breast and ovarian cancer risk reduction and mortality in BRCA mutation carriers.

Results

Bilateral risk-reducing mastectomy provides a 90% to 95% risk reduction in BRCA mutation carriers, although the data do not demonstrate improved mortality. The reduction in ovarian and breast cancer risks using risk-reducing bilateral salpingo-oophorectomy has translated to improvement in survival.

Conclusions

Clinical management of patients at increased risk for breast cancer requires consideration of risk, patient preference, and quality of life.

Section snippets

Search strategy

The preferred reporting items for systematic reviews and meta-analyses statement was followed to perform the systematic review that included trials without any restrictions on publication date. The last search was carried out on January 16, 2016. A review of surgical management strategies for BRCA mutation carriers was performed by searching the electronic databases PubMed, OVID MEDLINE, and Scopus. The terms “risk reduction,” “risk reducing,” “prophylactic,” “BRCA1,” “BRCA2,” “BRCA,” and

Results

Our literature search for prophylactic or risk-reducing mastectomy in BRCA patients identified 1,902 articles through PubMed, OVID MEDLINE, and Scopus. After excluding case reports, reviews, comments, editorial, and letters and non-English publications, 1,085 records remained. After duplicates were removed, there were 495 records. A total of 483 records were excluded because they were not relevant to the review leaving 12 full-text articles assessed for eligibility. An additional 2 were

Breast cancer risk reduction

A total of 10 studies specifically described the incidence of breast cancers after bilateral risk-reducing mastectomies (BRRM).14, 15, 16, 17, 18, 19, 20, 21, 22, 23 They demonstrated a significant risk reduction in the incidence of breast cancer with BRRM ranging from 89.5% to 100% (Table 2). A total of 5 of these studies compared BRRM with surveillance15, 16, 18, 19, 20 and 5 only described the incidence of occult cancers at surgery and in follow-up after BRRM.14, 17, 21, 22, 23 Of the 10

Ovarian cancer risk reduction

A total of 8 studies had cancer occurrence as an outcome, including ovarian cancer, fallopian tube cancer, and primary peritoneal carcinoma.16, 24, 25, 26, 27, 28, 29, 30 Of all the studies, 6 compared surveillance to surgery,16, 24, 26, 28, 29, 30 (Table 3) whereas 2 reported the prevalence of occult cancers and risk of primary peritoneal carcinoma after RRBSO.25, 27

The 6 studies comparing RRBSO to surveillance reported a profound reduction in ovarian cancer risk, ranging from 72% to 88%.16, 23

Comments

This systematic review addresses the question of whether RRBSO and/or BRRM is beneficial for BRCA mutation carriers with respect to risk reduction and mortality. Primary studies of BRCA mutation carriers who have undergone BRRM in this review demonstrate a significant risk reduction in breast cancer incidence. The risk of breast cancer after BRRM is less than 3%, and the risk reduction appears to be equal in both BRCA1 and BRCA2 mutation carriers (Table 2).14, 15, 16, 17, 18, 19, 20, 21, 22, 23

Individualized decision making

With the increasing indications for genetic testing that are constantly changing,9 more women will be diagnosed with BRCA mutations. Currently, it is not feasible to personalize BRCA carriers' cancer risk based on the specific deleterious mutation. Instead, average risk among a group of carriers with a representative mix of mutations in the population must be calculated. One of the most comprehensive studies of BRCA1 and BRCA2 penetrance found that the mean cumulative cancer risks for mutation

Conclusions

In summary, our systematic review aimed to determine whether prophylactic surgery improves outcomes in unaffected BRCA carriers. The data presented here confirm both BRRM and RRBSO result in a reduction in both breast and ovarian cancers. Improvement in ovarian cancer–related and all-cause mortality was seen with RRBSO with moderate-quality data. However, this improvement was not seen with BRRM as the data were of low quality. Need for longer follow-up and heterogeneity in reporting contribute

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    The authors declare no conflicts of interest.

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