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Contralateral Mastectomy After Unilateral Breast Cancer

Contralateral Mastectomy After Unilateral Breast Cancer

Abstract and Introduction

Abstract


Objective To examine whether contralateral prophylactic mastectomy (CPM) is associated with improved survival, incidence of contralateral breast cancer (CBC), and recurrence in patients with unilateral breast cancer (UBC).

Background Despite conflicting data, CPM rates continue to increase. Here we present the first meta-analysis to assess post-CPM outcomes in women with UBC.

Methods We searched 5 databases and retrieved papers' bibliographies for relevant studies published through March 2012. Fixed- and random-effects meta-analyses were conducted on the basis of tests of study heterogeneity. We examined potential confounding via stratification and meta-regression. We report pooled relative risks (RRs) and risk differences (RDs) with 95% confidence intervals (CIs) at 2-tailed P < 0.05 significance.

Results Of 93 studies reviewed, 14 were included in meta-analyses. Compared with nonrecipients, CPM recipients had higher rates of overall survival [OS; RR = 1.09 (95% CI: 1.06, 1.11)] and lower rates of breast cancer–specific mortality [BCM; RR = 0.69 (95% CI: 0.56, 0.85)] but saw no absolute reduction in risk of metachronous CBC (MCBC). Among patients with elevated familial/genetic risk (FGR, ie, BRCA carrier status and/or family history of breast cancer), both relative and absolute risks of MCBC were significantly decreased among CPM recipients [RR = 0.04 (95% CI: 0.02, 0.09); RD = −24.0% (95% CI: −35.6%, −12.4%)], but there was no improvement in OS or BCM.

Conclusions CPM is associated with decreased MCBC incidence but not improved survival among patients with elevated FGR. The superior outcomes observed when comparing CPM recipients with nonrecipients in the general population are likely not attributable to a CPM-derived decrease in MCBC incidence. UBC patients without known FGR should not be advised to undergo CPM.

Introduction


Despite an overall trend toward less invasive oncologic care in the United States, rates of contralateral prophylactic mastectomy (CPM) in women diagnosed with unilateral breast cancer (UBC) have more than doubled over the past 15 years. The increased prevalence of CPM is thought to reflect pervasive overestimation of metachronous contralateral breast cancer (MCBC) risk by breast cancer patients, increased dissemination of personalized genetic and immunohistochemical information to patients, improved postmastectomy reconstruction options, and exposure to internet-based information that is often contradictory. It is unclear whether CPM is associated with improved survival or decreased recurrence in UBC patients, all of whom are at increased risk for MCBC, that is, contralateral breast cancer (CBC) diagnosed subsequent to an index cancer. Definitions of MCBC vary throughout the literature. Depending on a given researcher's decision as to what period of time is sufficiently long to distinguish a synchronous contralateral breast cancer (SCBC) from a metachronous one, MCBC has been defined as a new CBC diagnosed anywhere from 1 month to 2 years after an index tumor. But the magnitude of MCBC risk is not uniformly distributed among patients with UBC: among women without a BRCA mutation, less than 10% would be expected to eventually develop MCBC, but among women with a family history of breast cancer and/or an identified genetic mutation in BRCA1 or BRCA2, incidence of MCBC has been estimated to be anywhere from 12% to 47%. CPM has historically been prescribed for these higher risk patients as a means through which to decrease MCBC and, concomitantly, mortality associated with MCBC. But even among this subset of breast cancer patients, the efficacy of CPM in improving long-term clinical outcomes is questionable.

Mirroring the difficulties of establishing a uniform definition of MCBC, survival—overall, breast-cancer-specific, and disease-free—in women with UBC has been defined in variable ways throughout the literature, and reports of the potential survival benefit CPM might confer on recipients have been similarly inconsistent. Among recent studies examining the relationship between CPM and overall survival (OS), neither Chung and colleagues' 2012 study nor the 2000 study by Peralta et al demonstrated a CPM-associated benefit with regard to OS. Peralta and colleagues did, however, report prolonged disease-free survival (DFS), defined as time to any breast cancer event (namely, a recurrent or second primary breast cancer including newly diagnosed CBCs) among CPM recipients. In contrast, the Bedrosian et al study based on Surveillance, Epidemiology, and End Results (SEER) data, the Boughey et al study from the Mayo Clinic, and the Herrinton et al Cancer Research Network study all reported an OS advantage potentially conferred by CPM; however, there are important subtleties in their findings. In the SEER data study by Bedrosian and colleagues, the observed CPM-associated survival benefit demonstrated in the full analysis was found in subgroup analysis to stem largely from the strong survival benefit (4.8%) conferred on young (ie, younger than 50 years) CPM recipients with early-stage (I and II), estrogen-receptor (ER)-negative disease who—by virtue of having more years to live and more aggressive tumor biology at baseline—had a higher absolute lifetime risk of MCBC compared with their older and ER-positive counterparts. In their cohort, Boughey et al found CPM to be associated with improved OS but not with breast cancer–specific survival and this discrepancy could be ascribed to CPM recipients' being healthier at baseline, a conjecture supported by the fact that the 9% survival difference between recipients and nonrecipients was greater than the absolute rate of CBCs in nonrecipients (8.1%). Finally, in the Herrinton et al study, the 3.6% difference in breast cancer–specific mortality (BCM) between CPM recipients and nonrecipients (8.1% vs 11.7%) is greater than the absolute reduction in CBC (0.5% vs 2.7%), making it difficult to attribute the difference in disease-specific mortality to the effects of CPM and suggesting there may be some other contributing factor. Thus, it is unclear to what extent the observed survival benefit reported in these studies is secondary to decreased (though, notably, not eliminated) risk of MCBC after removal of contralateral breast tissue; selection bias, specifically confounding patient characteristics, such as younger age, that are both independently associated with better baseline health and a greater likelihood of undergoing CPM; or to receipt of treatments—such as, tamoxifen and bilateral oophorectomy—that decrease the risk of BCM and/or all-cause mortality.

Here, we present the results of a systematic review and meta-analysis of CPM in female patients with a personal history of UBC. Although a Cochrane review on prophylactic mastectomy (both CPM in UBC patients as well as bilateral prophylactic mastectomy for prevention of a first breast cancer) was published in 2004 and updated in 2010, our review is the first to include meta-analyses of clinical outcomes, focuses solely on CPM as a method of risk reduction in patients with breast cancer diagnoses, and includes several large-scale studies published after the Cochrane review's 2010 update. Our intention is to provide a quantitative summation of current evidence that can serve as a succinct guide for clinical practice and can inform the development of future research examining the efficacy of CPM in both average- and high-risk breast cancer patients.



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