This systematic review reveals tendency for sound scientific methodology in HRQoL to be undermined by poorly designed and underpowered studies. In the current healthcare environment, patients and providers increasingly seek meaningful data to guide clinical decisions; policy makers are similarly in need of a rigorous patient-centered, comparative effectiveness data to inform national level decision-making. In light of this and the limitations of the existing published data, there is a pressing need for further Level I and II evidence in the form of randomized controlled trials as well as well-designed, multicenter prospective longitudinal studies in breast reconstruction. Such studies should incorporate sensitive and condition-specific patient-report outcome measures, provide adequate sample sizes, and respect established guidelines for rigorous HRQoL methodology.

The prognosis for women with breast cancer is adversely affected by the comorbidities of obesity and diabetes mellitus (DM), which are conditions associated with elevated levels of circulating fatty acids, hyperglycaemia and hyperinsulinaemia. We investigated the effects of exposure of nonmalignant and malignant human breast epithelial cells to elevated levels of fatty acids and glucose on their growth, survival and response to chemotherapeutic agents. We found that palmitate induced cell death in the non-malignant cells but not in the malignant cells, which was abrogated through the inhibition of ceramide production and by oleate but not by IGF1. Fatty acid synthase (FAS) is responsible for the de novo synthesis of fatty acids from sugars, and is over-expressed in many epithelial cancers. Abundance of FAS was higher in malignant cells than in non-malignant cells, and was up-regulated by IGF1 in both cell types. IGF-induced growth of non-malignant cells was unaffected by suppression of FAS expression, whereas that of malignant cells was blocked as was their resistance to palmitate-induced cell death. Palmitate did not affect cell proliferation, whereas oleate promoted the growth of non-malignant cells but had the opposite effect, that is, inhibition of IGF1-induced growth of malignant cells. However, when the phosphatidylinositol 3-kinase pathway was inhibited, oleate enhanced IGF1-induced growth in both cell types. Hyperglycaemia conferred resistance on malignant cells, but not on non-malignant cells, to chemotherapy-induced cell death. This resistance was overcome by inhibiting FAS or ceramide production. Understanding the mechanisms involved in the associations between obesity, DM and breast cancer may lead to more effective treatment regimens and new therapeutic targets.

IntroductionHER-2 is one of four Erb B family-type I receptor tyrosine kinases and is the preferred dimerisation partner for the epidermal growth factor receptor [1,2]. The Erb B receptors are important in normal development and in human cancer. HER-2, independent of its own ligand, activates other Erb B receptors to increase their ligand affinity and to amplify biological responses. HER-2 plays a key role in activating cytoplasmic signalling through the phosphatidylinositol-3 kinase (PI-3K)/protein kinase B (Akt) and mitogen-activated protein kinase pathways to influence transcription of nuclear genes [2][3][4]. Activation of PI-3K/Akt is involved in cell proliferation and confers resistance to apoptosis [5,6]. Breast cancer is associated with Akt = protein kinase B; CDK = cyclin-dependent kinases; ELISA = enzyme-linked immunosorbent assay; ER = oestrogen receptor; IDS = intensity distribution score; NPI = Nottingham Prognostic Index; OS = overall survival; PI-3K = phosphatidylinositol-3 kinase; RFS = relapse-free survival. Breast Cancer Research AbstractBackground HER-2 (c-erbB2/Neu) predicts the prognosis of and may influence treatment responses in breast cancer. HER-2 activity induces the cytoplasmic location of p21 WAFI/CIPI in cell culture, accompanied by resistance to apoptosis. p21 WAFI/CIPI is a cyclin-dependent kinase inhibitor activated by p53 to produce cell cycle arrest in association with nuclear localisation of p21 WAFI/CIPI . We previously showed that higher levels of cytoplasmic p21 WAFI/CIPI in breast cancers predicted reduced survival at 5 years. The present study examined HER-2 and p21 WAFI/CIPI expression in a series of breast cancers with up to 9 years of follow-up, to evaluate whether in vitro findings were related to clinical data and the effect on outcome.

BackgroundThe clinical effectiveness of treating ipsilateral multifocal (MF) and multicentric (MC) breast cancers using breast‐conserving surgery (BCS) compared with the standard of mastectomy is uncertain. Inconsistencies relate to definitions, incidence, staging and intertumoral heterogeneity. The primary aim of this systematic review was to compare clinical outcomes after BCS versus mastectomy for MF and MC cancers, collectively defined as multiple ipsilateral breast cancers (MIBC).MethodsComprehensive electronic searches were undertaken to identify complete papers published in English between May 1988 and July 2015, primarily comparing clinical outcomes of BCS and mastectomy for MIBC. All study designs were included, and studies were appraised critically using the Newcastle–Ottawa Scale. The characteristics and results of identified studies were summarized.ResultsTwenty‐four retrospective studies were included in the review: 17 comparative studies and seven case series. They included 3537 women with MIBC undergoing BCS; breast cancers were defined as MF in 2677 women, MC in 292, and reported as MIBC in 568. Six studies evaluated MIBC treated by BCS or mastectomy, with locoregional recurrence (LRR) rates of 2–23 per cent after BCS at median follow‐up of 59·5 (i.q.r. 56–81) months. BCS and mastectomy showed apparently equivalent rates of LRR (risk ratio 0·94, 95 per cent c.i. 0·65 to 1·36). Thirteen studies compared BCS in women with MIBC versus those with unifocal cancers, reporting LRR rates of 2–40 per cent after BCS at a median follow‐up of 64 (i.q.r. 57–73) months. One high‐quality study reported 10‐year actuarial LRR rates of 5·5 per cent for BCS in 300 women versus 6·5 per cent for mastectomy among 887 women.ConclusionThe available studies were mainly of moderate quality, historical and underpowered, with limited follow‐up and biased case selection favouring BCS rather than mastectomy for low‐risk patients. The evidence was inconclusive, weakening support for the St Gallen consensus and supporting a future randomized trial.