Capsular contracture is the most common complication following implant based breast surgery and is one of the most common reasons for reoperation. Therefore, it is important to try and understand why this happens, and what can be done to reduce its incidence. A literature search using the MEDLINE database was conducted including search terms 'capsular contracture breast augmentation', 'capsular contracture pathogenesis', 'capsular contracture incidence', and 'capsular contracture management', which yielded 82 results which met inclusion criteria. Capsular contracture is caused by an excessive fibrotic reaction to a foreign body (the implant) and has an overall incidence of 10.6%. Risk factors that were identified included the use of smooth (vs. textured) implants, a subglandular (vs. submuscular) placement, use of a silicone (vs. saline) filled implant and previous radiotherapy to the breast. The standard management of capsular contracture is surgical via a capsulectomy or capsulotomy. Medical treatment using the off-label leukotriene receptor antagonist Zafirlukast has been reported to reduce severity and help prevent capsular contracture from forming, as has the use of acellular dermal matrices, botox and neopocket formation. However, nearly all therapeutic approaches are associated with a significant rate of recurrence. Capsular contracture is a multifactorial fibrotic process the precise cause of which is still unknown. The incidence of contracture developing is lower with the use of textured implants, submuscular placement and the use of polyurethane coated implants. Symptomatic capsular contracture is usually managed surgically, however recent research has focussed on preventing capsular contracture from occurring, or treating it with autologous fat transfer.

The CCN family members cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/ CCN2) and nephroblastoma over-expressed (Nov/CCN3) play diverse roles in cells, are known to regulate cell growth, adhesion, matrix production and migration and are involved in endocrineregulated pathways in various cell types. The role of these molecules in cancer remains controversial. In a cohort of 122 human breast tumours (together with 32 normal breast tissues) we have analysed the expression of all three CCN members at the mRNA and protein levels. Significantly higher levels of Cyr61 ðP ¼ 0:02Þ, but low levels of CTGF and Nov, were seen in tumour tissues compared with normal tissues. Significantly raised levels of Cyr61 were associated with poor prognosis ðP ¼ 0:02Þ, nodal involvement ðP ¼ 0:03Þ and metastatic disease ðP ¼ 0:016Þ. Patients who died of breast cancer also had high levels of Cyr61. In contrast, CTGF in patients with poor prognosis ðP ¼ 0:021Þ, metastasis ðP ¼ 0:012Þ, local recurrence ðP ¼ 0:0024Þ and mortality ðP ¼ 0:0072Þ had markedly reduced levels. Similar to CTGF, low levels of Nov were also seen in patients with poor prognosis and mortality and with significantly decreased survival (P ¼ 0:033 and P ¼ 0:0146, respectively). This result was fully supported by immunohistochemical analysis of frozen sectioned tissues. While fibroblasts and endothelial cells generally expressed good levels of all three CCN proteins, highly invasive MDA MB 231 cells expressed lower levels of CTGF and Nov, but higher levels of Cyr61, than the less invasive MCF-7. It is concluded that members of the CCN family are differentially expressed and may play important but contrasting roles in the progressive nature of human breast cancer. While Cyr61 appears to act as a factor stimulating aggressiveness, CTGF and Nov may act as tumour suppressors.

BackgroundSuppressors of cytokine signaling (SOCS) are important negative feedback regulators of the JAK/STAT signaling pathway, and have been recently investigated for their role in the development of different cancers. In this study, we examined the expression of SOCS1-7 genes in normal and breast cancer tissue and correlated this with several clinico-pathological and prognostic factors.MethodsSOCS1-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples (n = 127) and normal background breast tissue (n = 31). Transcript levels of expression were determined using real-time PCR and analyzed against TNM stage, tumour grade and clinical outcome over a 10 year follow-up period.ResultsSOCS1,4,5,6 and 7 expression decreased with increased TNM stage (TNM1 vs. TNM3 p = 0.039, TNM1 vs. TNM4 p = 0.016, TNM2 vs. TNM4 p = 0.025, TNM1 vs. TNM3 p = 0.012, and TNM1 vs. TNM3 p = 0.044 respectively). SOCS2 and 3 expression decreased with increased Nottingham Prognostic Index (NPI) (NPI1 vs. NPI3 p = 0.033, and NPI2 vs. NPI3 p = 0.041 respectively). SOCS7 expression decreased with higher tumour grade (Grade 3 vs. Grade 2 p = 0.037). After a median follow up period of 10 years, we found higher levels of SOCS1,2 and 7 expression among those patients who remained disease-free compared to those who developed local recurrence (p = 0.0073, p = 0.021, and p = 0.039 respectively). Similarly, we found higher levels of SOCS 2,4, and 7 expression in those who remained disease-free compared to those who developed distant recurrence (p = 0.022, p = 0.024, and p = 0.033 respectively). Patients who remained disease-free had higher levels of SOCS1 and 2 expression compared to those who died from breast cancer (p = 0.02 and p = 0.033 respectively). The disease free survival (DFS) and overall survival (OS) curves showed that higher levels of SOCS1, 3 and 7 were significant predictors of higher DFS (p = 0.015, p = 0.024 and 0.03 respectively) and OS (p = 0.005, p = 0.013 and p = 0.035 respectively). Higher levels of SOCS 4 were significant in predicting better OS (p = 0.007) but not DFS. Immunohistochemical staining of representative samples showed a correlation between SOCS1, 3, 7 protein staining and the SOCS1, 3, 7 mRNA expression.ConclusionHigher mRNA expression levels of SOCS1, 3, 4 and 7 are significantly associated with earlier tumour stage and better clinical outcome in human breast cancer.

Nipple-sparing mastectomy (NSM) is increasingly popular as a procedure for the treatment of breast cancer and as a prophylactic procedure for those at high risk of developing the disease. However, it remains a controversial option due to questions regarding its oncological safety and concerns regarding locoregional recurrence. This systematic review with a pooled analysis examines the current literature regarding NSM, including locoregional recurrence and complication rates. Systematic electronic searches were conducted using the PubMed database and the Ovid database for studies reporting the indications for NSM and the subsequent outcomes. Studies between January 1970 and January 2015 (inclusive) were analysed if they met the inclusion criteria. Pooled descriptive statistics were performed. Seventy-three studies that met the inclusion criteria were included in the analysis, yielding 12,358 procedures. After a mean follow up of 38 months (range, 7.4–156 months), the overall pooled locoregional recurrence rate was 2.38%, the overall complication rate was 22.3%, and the overall incidence of nipple necrosis, either partial or total, was 5.9%. Significant heterogeneity was found among the published studies and patient selection was affected by tumour characteristics. We concluded that NSM appears to be an oncologically safe option for appropriately selected patients, with low rates of locoregional recurrence. For NSM to be performed, tumours should be peripherally located, smaller than 5 cm in diameter, located more than 2 cm away from the nipple margin, and human epidermal growth factor 2-negative. A separate histopathological examination of the subareolar tissue and exclusion of malignancy at this site is essential for safe oncological practice. Long-term follow-up studies and prospective cohort studies are required in order to determine the best reconstructive methods.