Skin-sparing mastectomy for the treatment of breast cancer.

BACKGROUND: Skin-sparing mastectomy (SSM) is a surgical technique that aims to maximize skin preservation, facilitate breast reconstruction, and improve cosmetic outcomes. Despite its use in clinical practice, the benefits and harms related to SSM are not well established. OBJECTIVES: To assess the effectiveness and safety of skin-sparing mastectomy for the treatment of breast cancer. SEARCH METHODS: We searched Cochrane Breast Cancer's Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov on 9 August 2019. SELECTION CRITERIA: Randomized controlled trials (RCTs), quasi-randomized or non-randomized studies (cohort and case-control) comparing SSM to conventional mastectomy for treating ductal carcinoma in situ (DCIS) or invasive breast cancer. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcome was overall survival. Secondary outcomes were local recurrence free-survival, adverse events (including overall complications, breast reconstruction loss, skin necrosis, infection and hemorrhage), cosmetic results, and quality of life. We performed a descriptive analysis and meta-analysis of the data. MAIN RESULTS: We found no RCTs or quasi-RCTs. We included two prospective cohort studies and twelve retrospective cohort studies. These studies included 12,211 participants involving 12,283 surgeries (3183 SSM and 9100 conventional mastectomies). It was not possible to perform a meta-analysis for overall survival and local recurrence free-survival due to clinical heterogeneity across studies and a lack of data to calculate hazard ratios (HR).  Based on one study, the evidence suggests that SSM may not reduce overall survival for participants with DCIS tumors (HR 0.41, 95% CI 0.17 to 1.02; P = 0.06; 399 participants; very low-certainty evidence) or for participants with invasive carcinoma (HR 0.81, 95% CI 0.48 to 1.38; P = 0.44; 907 participants; very low-certainty evidence). For local recurrence-free survival, meta-analysis was not possible, due to high risk of bias in nine of the ten studies that measured this outcome. Informal visual examination of effect sizes from nine studies suggested the size of the HR may be similar between groups. Based on one study that adjusted for confounders, SSM may not reduce local recurrence-free survival (HR 0.82, 95% CI 0.47 to 1.42; P = 0.48; 5690 participants; very low-certainty evidence).  The effect of SSM on overall complications is unclear (RR 1.55, 95% CI 0.97 to 2.46; P = 0.07, I2 = 88%; 4 studies, 677 participants; very low-certainty evidence). Skin-sparing mastectomy may not reduce the risk of breast reconstruction loss (RR 1.79, 95% CI 0.31 to 10.35; P = 0.52; 3 studies, 475 participants; very low-certainty evidence), skin necrosis (RR 1.15, 95% CI 0.62 to 2.12; P = 0.22, I2 = 33%; 4 studies, 677 participants; very low-certainty evidence), local infection (RR 2.04, 95% CI 0.03 to 142.71; P = 0.74, I2 = 88%; 2 studies, 371 participants; very low-certainty evidence), nor hemorrhage (RR 1.23, 95% CI 0.47 to 3.27; P = 0.67, I2 = 0%; 4 studies, 677 participants; very low-certainty evidence). We downgraded the certainty of the evidence due to the risk of bias, imprecision, and inconsistency among the studies. There were no data available on the following outcomes: systemic surgical complications, local complications, explantation of implant/expander, hematoma, seroma, rehospitalization, skin necrosis with revisional surgery, and capsular contracture of the implant. It was not possible to perform a meta-analysis for cosmetic and quality of life outcomes due to a lack of data. One study performed an evaluation of aesthetic outcome after SSM: 77.7% of participants with immediate breast reconstruction had an overall aesthetic result of excellent or good versus 87% of participants with delayed breast reconstruction. AUTHORS' CONCLUSIONS: Based on very low-certainty evidence from observational studies, it was not possible to draw definitive conclusions on the effectiveness and safety of SSM for breast cancer treatment. The decision for this technique of breast surgery for treatment of DCIS or invasive breast cancer must be individualized and shared between the physician and the patient while considering the potential risks and benefits of available surgical options.

Breast surgery for metastatic breast cancer.

BACKGROUND: Metastatic breast cancer is not a curable disease, but women with metastatic disease are living longer. Surgery to remove the primary tumour is associated with an increased survival in other types of metastatic cancer. Breast surgery is not standard treatment for metastatic disease, however several recent retrospective studies have suggested that breast surgery could increase the women's survival. These studies have methodological limitations including selection bias. A systematic review mapping all randomised controlled trials addressing the benefits and potential harms of breast surgery is ideal to answer this question. OBJECTIVES: To assess the effects of breast surgery in women with metastatic breast cancer. SEARCH METHODS: We conducted searches using the MeSH terms 'breast neoplasms', 'mastectomy', and 'analysis, survival' in the following databases: the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (by PubMed) and Embase (by OvidSP) on 22 February 2016. We also searched ClinicalTrials.gov (22 February 2016) and the WHO International Clinical Trials Registry Platform (24 February 2016). We conducted an additional search in the American Society of Clinical Oncology (ASCO) conference proceedings in July 2016 that included reference checking, citation searching, and contacting study authors to identify additional studies. SELECTION CRITERIA: The inclusion criteria were randomised controlled trials of women with metastatic breast cancer at initial diagnosis comparing breast surgery plus systemic therapy versus systemic therapy alone. The primary outcomes were overall survival and quality of life. Secondary outcomes were progression-free survival (local and distant control), breast cancer-specific survival, and toxicity from local therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted trial selection, data extraction, and 'Risk of bias' assessment (using Cochrane's 'Risk of bias' tool), which a third review author checked. We used the GRADE tool to assess the quality of the body of evidence. We used the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes and the hazard ratio (HR) for time-to-event outcomes. We calculated 95% confidence intervals (CI) for these measures. We used the random-effects model, as we expected clinical or methodological heterogeneity, or both, among the included studies. MAIN RESULTS: We included two trials enrolling 624 women in the review. It is uncertain whether breast surgery improves overall survival as the quality of the evidence has been assessed as very low (HR 0.83, 95% CI 0.53 to 1.31; 2 studies; 624 women). The two studies did not report quality of life. Breast surgery may improve local progression-free survival (HR 0.22, 95% CI 0.08 to 0.57; 2 studies; 607 women; low-quality evidence), while it probably worsened distant progression-free survival (HR 1.42, 95% CI 1.08 to 1.86; 1 study; 350 women; moderate-quality evidence). The two included studies did not measure breast cancer-specific survival. Toxicity from local therapy was reported by 30-day mortality and did not appear to differ between the two groups (RR 0.99, 95% CI 0.14 to 6.90; 1 study; 274 women; low-quality evidence). AUTHORS' CONCLUSIONS: Based on existing evidence from two randomised clinical trials, it is not possible to make definitive conclusions on the benefits and risks of breast surgery associated with systemic treatment for women diagnosed with metastatic breast cancer. Until the ongoing clinical trials are finalised, the decision to perform breast surgery in these women should be individualised and shared between the physician and the patient considering the potential risks, benefits, and costs of each intervention.

Nipple- and areola-sparing mastectomy for the treatment of breast cancer.

BACKGROUND: The efficacy and safety of nipple-sparing mastectomy and areola-sparing mastectomy for the treatment of breast cancer are still questionable. It is estimated that the local recurrence rates following nipple-sparing mastectomy are very similar to breast-conserving surgery followed by radiotherapy. OBJECTIVES: To assess the efficacy and safety of nipple-sparing mastectomy and areola-sparing mastectomy for the treatment of ductal carcinoma in situ and invasive breast cancer in women. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialized Register, the Cochrane Center Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), Embase (via OVID) and LILACS (via Biblioteca Virtual em Saúde [BVS]) using the search terms "nipple sparing mastectomy" and "areola-sparing mastectomy". Also, we searched the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov. All searches were conducted on 30th September 2014 and we did not apply any language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) however if there were no RCTs, we expanded our criteria to include non-randomised comparative studies (cohort and case-control studies). Studies evaluated nipple-sparing and areola-sparing mastectomy compared to modified radical mastectomy or skin-sparing mastectomy for the treatment of ductal carcinoma in situ or invasive breast cancer. DATA COLLECTION AND ANALYSIS: Two review authors (BS and RR) performed data extraction and resolved disagreements. We performed descriptive analyses and meta-analyses of the data using Review Manager software. We used Cochrane's risk of bias tool to assess studies, and adapted it for non-randomised studies, and we evaluated the quality of the evidence using GRADE criteria. MAIN RESULTS: We included 11 cohort studies, evaluating a total of 6502 participants undergoing 7018 procedures: 2529 underwent a nipple-sparing mastectomy (NSM), 818 underwent skin-sparing mastectomy (SSM) and 3671 underwent traditional mastectomy, also known as modified radical mastectomy (MRM). No participants underwent areola-sparing mastectomy. There was a high risk of confounding for all reported outcomes. For overall survival, the hazard ratio (HR) for NSM compared to SSM was 0.70 (95% CI 0.28 to 1.73; 2 studies; 781 participants) and the HR for NSM compared to MRM was 0.72 (95% CI 0.46 to 1.13; 2 studies, 1202 participants). Local recurrence was evaluated in two studies, the HR for NSM compared to MRM was 0.28 (95% CI 0.12 to 0.68; 2 studies, 1303 participants). The overall risk of complications was different in NSM when compared to other types of mastectomy in general (RR 0.10, 95% CI 0.01 to 0.82, 2 studies, P = 0.03; 1067 participants). With respect to skin necrosis, there was no evidence of a difference with NSM compared to other types of mastectomy, but the confidence interval was wide (RR 4.22, 95% CI 0.59 to 30.03, P = 0.15; 4 studies, 1948 participants). We observed no difference among the three types of mastectomy with respect to the risk of local infection (RR 0.95, 95% CI 0.44 to 2.09, P = 0.91, 2 studies; 496 participants). Meta-analysis was not possible when assessing cosmetic outcomes and quality of life, but in general the NSM studies reported a favourable aesthetic result and a gain in quality of life compared with the other types of mastectomy. The quality of evidence was considered very low for all outcomes due to the high risk of selection bias and wide confidence intervals. AUTHORS' CONCLUSIONS: The findings from these observational studies of very low-quality evidence were inconclusive for all outcomes due to the high risk of selection bias.