Breast cancer (BC) is the most common malignant tumor in women, obesity is associated with increased BC incidence and mortality and high levels of circulating insulin may negatively impact on cancer incidence. In the present study, we investigated whether the strength of several anthropometric and metabolic parameters varies between BC molecular subtypes. Eligible cases were 991 non-metastatic BC patients recruited between January 2009 and December 2013. Anthropometric, clinical and immunohistochemical features were measured. Multivariate logistic regression models were built to assess HER2 positive BC risk, comparing (a) triple positive (TP) with luminal A, luminal B and triple negative (TN) and (b) HER2-enriched group with luminal A, luminal B and TN. We stratified patients in pre- and post-menopause: significant differences emerged for luminal A in relation to age: they were more likely to be older compared to other groups. Among postmenopausal patients, the adjusted multivariate analysis showed that high BMI and high waist circumference were inversely correlated to TP subtype when compared to luminal B (OR=0.48 and OR=0.49, respectively). Conversely, HOMA-IR was a risk factor for TP when compared to luminal A and TN (OR=2.47 and OR=3.15, respectively). Our findings suggest a potential role of higher abdominal fat in the development of specific BC molecular subtypes in postmenopausal women. Moreover, they support a potential role of insulin resistance in the development of HER2 positive BC, although this role appears to be stronger when hormone receptors are co-expressed, suggesting a difference in the etiology of these two BC subtypes.

BACKGROUND:Intraoperative radiotherapy (IORT) constitutes a paradigm shift from the conventional 3-5 weeks of whole-breast external beam radiotherapy (EBRT). IORT enables delivery of radiation at the time of excision of the breast tumour, targeting the area at highest risk of recurrence, while minimizing excessive radiation exposure to healthy breast tissue. The rationale for IORT is based on the observation that over 90 per cent of local recurrences after breast-conserving surgery occur at or near the original operation site.METHODS:This article reviews trials of IORT delivered with different techniques and devices.RESULTS:IORT is a very attractive option for delivering radiotherapy, reducing the traditional fractionated treatment to a single fraction administered at the time of surgery. IORT has been shown to be associated with reduced toxicity and has several potential benefits over EBRT. Only two randomized clinical trials have been published to date. The TARGIT-A and ELIOT trials have demonstrated that IORT is associated with a low rate of local recurrence, although higher than that after EBRT (TARGIT-A: 3·3 versus 1·3 per cent respectively, P = 0·042; ELIOT: 4·4 versus 0·4 per cent, P < 0·001). However, the local recurrence rate for IORT fell within the predefined 2·5 per cent non-inferiority margin in TARGIT-A, and the 7·5 per cent equivalence margin in ELIOT.CONCLUSION:Longer follow-up data from existing trials, optimization of patient criteria and cost-effectiveness analyses are needed. Based on the current evidence, IORT can be offered as an alternative to EBRT to selected patients within agreed protocols, and outcomes should be monitored within national registries.

In the last decade Ostreopsis cf. ovata blooms have been among the most intense along the entire Mediterranean coast, leading to ecological and human health problems, that are associated with the toxins (palytoxin-like compounds) produced by these algal cells. These compounds are secondary metabolites, whose rates of synthesis depend on the metabolism of their precursors. In general, growth dynamics and toxicity of dinoflagellates reflect the physiological status of the organism. The aim of the present study was to investigate the cellular production of the main biochemical compounds likely involved in the growth and toxicity dynamics of O. cf. ovata during exponential to the late stationary phase in batch cultures of an Adriatic strain. Removal of major nutrients from the medium was monitored along with concentration, biovolume and production of the main cellular components (e.g. polysaccharides, proteins, lipids and toxins). Nutrient uptake, as well as toxin production rates were calculated in the different growth periods. Nutrients (N and P) were completely depleted when cells entered stationary phase and the greatest net toxin production rate (RTOX) occurred during the first days of growth. The various palytoxins reported a relative abundance quite stable during the different growth phases, while the total toxin cellular amount increased along the growth curve. Total and extracellular released polysaccharides, as well as the lipid content increased greatly during the stationary phase, while proteins were mainly produced by cells during the exponential phase. The continuous release of polysaccharides could facilitate cell aggregation and the formation of the benthic community during algal blooms. The trend of production of the main cellular compounds in O. cf. ovata and the growth dynamics of this species lead us to hypothesize that the fast growth of this dinoflagellate, associated with the rapid use of environmental resources (nutrients, and phosphates in particular), may be an ecological/adaptive strategy which could favor this organism in competition with other species.

Aim: ErbB2 is overexpressed in about 25% of breast cancers. It modulates myocardial development and function in the heart. Trastuzumab (T), an anti-ErbB2 inhibitor, has improved the prognosis of patients with breast cancer, but is related to an increased risk of asymptomatic left ventricular (LV) dysfunction (3–34%) and heart failure (2–4%). The mechanisms of T cardiotoxicity are not entirely known and can include changes in Ca2+ regulation related to blockade of ErbB2. Here, we aim at assessing whether ranolazine (RAN), diminishing intracellular Ca2+ through its inhibition of late Ina, blunts T cardiotoxicity in vivo. Methods: To evaluate cardiac function in vivo, fractional shortening (FS) and ejection fraction (EF) were measured by echocardiography M-Mode in C57BL6 mice, 2-4 mo old, pretreated with RAN (750mg/kg/day, a dose comparable to the one used in humans) per os for 3 days. RAN was then administered for additional 7 days, alone and together with T (2.25 mg/kg/day ip), according to our well established protocol. Results: In our in vivo studies, after 7 days with T, FS decreased to 49 ± 1.5%, p < 0.01 vs 60 ± 0.5% (sham), and EF to 81 + 2%, p < 0.01 vs 91 ± 1% (sham). RAN alone did not change FS (59 ± 2%) nor EF 89 ± 1%. Interestingly, in mice treated with RAN and T, RAN prevents the reduction of EF and FS vs T alone (FS was 58 ± 1%, EF was 90 ± 1%, p = 0.01 and p < 0.01 respectively). Conclusions: In our mouse model, T produces LV dysfunction and RAN blunts T cardiotoxic effects. We plan to test RAN as a cardioprotective agent with other target-therapy drugs in our experimental models and to define the mechanisms of cardioprotection.

Background: Metabolic syndrome is considered to be associated with the increased risk of breast cancer. Epidemiologic data suggest that the strength of the metabolic syndrome–breast cancer link varies by intrinsic molecular subtype, but results from worldwide literature are controversial. Main aim of this study was to assess whether metabolic syndrome is associated to breast cancer specific subtype.

e12012 Background: The reasons for variation in breast cancer survival are multifactorial. In patients diagnosed with early breast cancer, evidence has emerged relatively to more favorable outcomes associated with disease detection in a screening context. Methods: To investigate whether mode of breast cancer detection may affect patient important outcomes following breast conservative therapy (BCT). We analyzed data on 448 patients with early breast cancer treated at the National Cancer Institute of Naples between January 2004 and June 2006. Breast cancers were categorized into mammography- and self-detected (MG and S-D) cases. The actuarial survival rates were calculated using the Kaplan–Meier method, and statistical significance differences between rates were evaluated by the log-rank test. Cox proportional hazard model was used for multivariate analysis including tumor characteristics, use of systemic therapy, and age to assess risk factors for local and distant metastasis free survival (LRFS, and DMFS respectively), and overall survival rates (OS). Results: The median follow up duration was 61,2 months (range 4-83). The 5-year DFS and OS for MG and S-D breast cancer cases were 89.7% and 73.1% (p = 0.001) and 93.5%.vs. 82.1 (p = 0.007), respectively. On multivariate analysis, mode of breast cancer was a significant predictor of DFS, with hazard ratio (HR) for MG detected cases being 2.11 (95% CI 1.04-4.86). In the same group, a suggestion for a predictor role on OS was given (HR 2.6, 95% CI 0.92-7.57). Conclusions: Following BCT, mammographic detected early breast cancer cases showed a significant advantage in terms of DFS and a non significant improvement in OS. mode of breast cancer detection might further add to the decision process leading to individualized patient management.

There has been progress in the identification of factors that confer important risk for the development of breast cancer.The factors include: heritable mutations in susceptibility genes; exposure to therapeutic radiation during breast development (as for Hodgkin's disease survivors who received therapeutic radiation to the chest); and histologic lesions, including LCIS and atypical hyperplasias.Testing for mutations in the BRCA1 and BRCA2 breast ovarian cancer susceptibility genes has become part of the established care of breast cancer patients.Genetic information from BRCA1/2 testing is used to help healthy at-risk women to avoid breast and/or ovarian cancer, and ultimately to avoid death from those cancers.Data accumulated over the past decade have provided evidence that breast cancer surveillance can be improved with the addition of breast MRI, that prophylactic oophorectomy substantially reduces the risk of ovarian cancer and, when performed before menopause, can reduce the risk of breast cancer as well, and that prophylactic mastectomy reduces the risk of breast cancer by more than 90%.It has been observed that approximately 80% of BRCA1-associated breast cancers are negative for ER, PR and HER2 (so-called triple negative) and cluster with basal-like breast cancers by DNA microarray, while 80% of BRCA2-associated breast cancers are ER + and PR + , but HER2 negative, and luminal.These data are surprising given the close relationships between these genes in their DNA repair activities, and raise some concern that hormonal interventions will not successfully reduce the risk of BRCA1-associated breast cancers.Other strategies may be necessary to reduce breast cancer risk for this group.Genetic information has been shown to have important implications for women with breast cancer as well.Women with strong family histories of breast and/or ovarian cancer, and women diagnosed before age 40 may consider testing at the time of breast cancer diagnosis if they would use the information to make treatment decisions.Some women choose bilateral mastectomies over breast-conserving treatment if they learn that their risk of second primary breast cancer exceeds 50%, and if their prognosis from the original breast cancer is good.Some women opt for oophorectomy as part of the management of their ER + breast cancer if they are premenopausal mutation carriers (and could participate in TEXT).Recently, novel agents, the PARP inhibitors, have been shown to be effective in the phase II trials in women with BRCA1 or BRCA2 mutations and metastatic ovarian or breast cancer.These drugs target DNA repair pathways that are particularly vulnerable in women with BRCA1/2 mutations.The agents may also be effective in women with sporadic breast cancer, and are currently in trials in Europe and the United States alone and in combination with cytotoxic agents. S2 Magnetic resonance imaging for diagnosis, staging, and follow-up

BACKGROUNDThe present article reports the updated survival outcome of the 200 patients enrolled in the Southern Italy Cooperative Oncology Group 9908 trial, which compared 12 weekly cycles of cisplatin-epirubicin-paclitaxel (PET) with 4 triweekly (once every 3 weeks) cycles of epirubicin-paclitaxel (ET) in patients with locally advanced breast cancer (LABC).METHODSThe effects of treatment, pathologically documented response (pathological response), pre- and post-treatment biomarkers on relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) are analysed.RESULTSAt a median follow-up of 74 (range 48-105 months) months, the 5-year RFS, DMFS, and OS were 64 % versus 53% (P = 0.11), 73% versus 55% (P = 0.04), and 82% versus 69% (P = 0.07) in PET and ET, respectively. At multivariate analysis, after adjusting treatment effect for pretreatment biomarkers, PET independently predicted better DMFS (P = 0.018) and OS (P = 0.03), whereas the impact on RFS was of borderline significance (0.057). PET treatment was significantly better than ET treatment only in high-grade or highly proliferating tumours. The better outcome in PET arm was the results of both the higher rate of patients with optimal pathological response and the lower rate of patients with biologically aggressive residual tumour.CONCLUSIONSThe PET weekly regimen significantly improves both DMFS and OS in LABC patients, compared with the triweekly ET combination. The therapeutic advantage is limited to patients with highly aggressive tumours.

The purpose of the current analysis was to evaluate the outcome of patients enrolled at the National Cancer Institute of Naples between 1997 and 2000, who underwent breast-conserving surgery. Between January 1997 and December 2000, 946 patients had been diagnosed with T1 or T2 (<= 3 cm) breast carcinoma. At the time of the present analysis (31-12-2005), all patients had been followed for >5 years. A Cox proportional hazards model was performed.Overall, 7-year Locoregional Relapse-free survival (LRFS) and Distant Relapse-free Survival (DRFS) rates were 95.9% and 88.4%, respectively. Seven-year DRFS was 91.2% and 79.3% in T1 and T2 stage, respectively (p<0.0001). Multivariate Cox analysis indicated that number of positive lymph-nodes and hormone receptor status were significantly associated with prognosis.Our findings confirm that early diagnosed breast cancer, treated with breast-conserving surgery, is associated with a very good prognosis in patients referred to an Institution which may be considered as representative of similar Cancer Institutes of Southern Italy. The risk of local relapse was found to be very low (4%), although a longer follow-up is needed to draw definitive conclusions.