Molecular subtyping confirms that breast cancer comprises at least four genetically distinct entities based on the expression of specific genes including estrogen receptor (ER), progesterone receptor (PR), and HER2/neu receptor. The quantitative influence of subtype on ipsilateral locoregional recurrence (LRR) is unknown. The aim of this study was to systematically appraise the influence of breast cancer subtype on LRR following breast conserving therapy (BCT) and mastectomy. A comprehensive search for studies examining outcomes after BCT and/or mastectomy according to breast cancer subtype was performed using Medline and cross-referencing available data. Reviews of each study were conducted and data extracted to perform meta-analysis. Primary outcome was LRR related to breast cancer subtype. A total of 12,592 breast cancer patients who underwent either BCT (n = 7,174) or mastectomy (n = 5,418) were identified from 15 studies. Patients with luminal subtype tumors (ER/PR +ve) had a lower risk of LRR than both triple-negative (RR 0.38; 95% CI 0.23-0.61); and HER2/neu-overexpressing (RR 0.34; 95% CI 0.26-0.45) tumors following BCT. Luminal tumors were also less likely to develop LRR than HER2/neu-overexpressing (OR 0.69; 95% CI 0.54-0.89) or triple-negative tumors (OR 0.61; 95% CI 0.46-0.79) after mastectomy. HER2/neu-overexpressing tumors have increased risk of LRR compared to triple-negative tumors (RR 1.44; 95% CI 1.06-1.95) following BCT but there was no difference in LRR between HER2/neu-overexpressing and triple-negative tumors following mastectomy (RR 0.91; 95% CI 0.68-1.22). Luminal tumors exhibit the lowest rates of LRR. Patients with triple-negative and HER2/neu-overexpressing breast tumors are at increased risk of developing LRR following BCT or mastectomy. Breast cancer subtype should be taken into account when considering local control and identifies those at increased risk of LRR, who may benefit from more aggressive local treatment.

BackgroundTreatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®).Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype.Scope of ReviewHow tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease.Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed.Major conclusionsCellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome.General SignificanceFocusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy.

Surgical margins negative for DCIS should be obtained after BCS for DCIS. A margin threshold of 2 mm seems to be as good as a larger margin when BCS for DCIS is combined with RT.

To cite this version:M Barry, M. R. Kell. Radiotherapy and breast reconstruction: a meta-analysis. Breast Cancer Research and Treatment, Springer Verlag, 2011, 127 (1) databases were searched and cross-referenced for appropriate studies where morbidity following BR was the primary outcome measured.. Results:1,105 patients were identified from 11 appropriately selected studies.Patients undergoing PMRT and BR are more likely to suffer morbidity compared to patients not receiving PMRT ((OR) = 4.2; 95% CI, 2.4-7.2(no PMRT vs. PMRT)). Reconstruction technique was also examined with outcome whenPMRT was delivered after BR and this demonstrated that autologous reconstruction is associated with less morbidity in this setting ((OR) = 0.21; (95% CI, 0.1-0.4 (autologous vs. implant based)). Delaying BR until after PMRT had no significant effect on outcome ((OR) =0.87; 95% CI, 0.47-1.62 (delayed vs. immediate)).Conclusions: PMRT has a detrimental effect on BR outcome. These results suggest that where immediate reconstruction is undertaken with the necessity of PMRT, an autologous flap results in less morbidity when compared to implant based reconstruction. 3 INTRODUCTION:Breast Eligibility CriteriaAll trials whether randomized or non-randomized, prospective or retrospective were eligible that examined the effects of radiotherapy on immediate or delayed breast reconstruction using either a prosthesis or autologous tissue (Latissimus Dorsi (LD) or Trasversus Rectus Abdominis Muscle (TRAM). Case series orreports were not included. Studies where the data could not be accurately extracted were also excluded. Data Extraction and OutcomesThe following information regarding each eligible trial was recorded: authors' names, journal, patient numbers, timing and method of reconstruction, addition of radiotherapy and the post-operative complication rate. The primary end point of 7 this meta-analysis was postoperative morbidity including capsular contracture, fibrosis, fat necrosis, surgical site infections requiring removal of prosthesis/reoperation (see tables 2, 4 and 6). Statistical AnalysisFor post-operative complications in each study, the odds ratio (O.R.) of the simple proportions of events was estimated with its variance and 95% CI.Heterogeneity between the O.R.s for the same outcome between studies was assessed by use of the X 2 -based Q statistic [24]. Data were then combined across studies by the use of general variance methods with fixed and random effects models [14]. Analyses were conducted using StatsDirect version 2.5.6(StatsDirect Ltd, Chesire, United Kingdom) and SPSS version 12.0 (SPSS, Inc, Chicago, IL). All statistical tests were two tailed. 8 RESULTS:Eligible Studies 20 potentially eligible studies were identified that examined the effects of radiotherapy on immediate or delayed breast reconstructions. 9 studies were excluded from the meta-analysis due to low numbers (e.g. n < 15) or incomplete data set regarding postoperative morbidity. Of the 11 studies selected, 4 were studies that examined the effects of RT...

Patients with stage IV disease undergoing surgical excision of the primary tumor achieve a superior survival rate then their nonsurgical counterparts. In the absence of robust evidence, this meta-analysis provides evidence base for primary resection in the setting of stage IV breast cancer for appropriately selected patients.