The Impact of Lifestyle Interventions in High-Risk Early Breast Cancer Patients: A Modeling Approach from a Single Institution Experience

none21noA healthy lifestyle plays a strategic role in the prevention of BC. The aim of our prospective study is to evaluate the effects of a lifestyle interventions program based on special exercise and nutrition education on weight, psycho-physical well-being, blood lipid and hormonal profile among BC patients who underwent primary surgery. From January 2014 to March 2017, a multidisciplinary group of oncologists, dieticians, physiatrists and an exercise specialist evaluated 98 adult BC female patients at baseline and at different time points. The patients had at least one of the following risk factors: BMI ≥ 25 Kg/m2, high testosterone levels, high serum insulin levels or diagnosis of MS. Statistically significant differences are shown in terms of BMI variation with the lifestyle interventions program, as well as in waist circumference and blood glucose, insulin and testosterone levels. Moreover, a statistically significant difference was reported in variations of total Hospital Anxiety and Depression Scale (HADS) score, in the anxiety HADS score and improvement in joint pain. Our results suggested that promoting a healthy lifestyle in clinical practice reduces risk factors involved in BC recurrence and ensures psycho-physical well-being.openMirco Pistelli, Valentina Natalucci, Laura Scortichini, Veronica Agostinelli, Edoardo Lenci, Sonia Crocetti, Filippo Merloni, Lucia Bastianelli, Marina Taus, Daniele Fumelli, Gloria Giulietti, Claudia Cola, Marianna Capecci, Roberta Serrani, Maria Gabriella Ceravolo, Maurizio Ricci, Albano Nicolai, Elena Barbieri, Giulia Nicolai, Zelmira Ballatore, Agnese Savini and Rossana BerardiPistelli, Mirco; Natalucci, Valentina; Scortichini, Laura; Agostinelli, Veronica; Lenci, Edoardo; Crocetti, Sonia; Merloni, Filippo; Bastianelli, Lucia; Taus, Marina; Fumelli, Daniele; Giulietti, Gloria; Cola, Claudia; Capecci, Marianna; Serrani, Roberta; Gabriella Ceravolo, Maria; Ricci, Maurizio; Nicolai, Albano; Barbieri, Elena; Nicolai, Giulia; Ballatore, Zelmira; Savini and Rossana Berardi, Agnes

Vegetation dynamics in coastal wetlands. An example in Northern Italy : the Bardello

The coastal freshwater wetlands are in Italy very rare. The vegetation of one of these zones has been studied with Braun-Blanquet method. If exception is made for Cyperetum flavescentis, directly determined by trampling, the remaining surveyed vegetation can be divided into two groups : psammophytic vegetation in the more elevated zones (Bromo tectorum-Pleetum arenarsii, Schoeneto-Chrysopogonetum grylli), and hygrophytic vegetation, linked to the dune slacks (Phragmitetum australis, Eleocharis uniglumis community, Juncus subnodulosus community, Allio suaveolentis-Molinietum. The correlation of vegetation types with the ecological indexes and the phytogeographical elementshas been studied by applying numerical methods. The main dynamical trend in the hygrophytic vegetation consists of a linear dynamical sere since the reeds evolve to Populetalia communities, Bromo-Phleetum, present in the most releved dunes could be considered as a long-lasting stage conditioned both natural and anthropic causes. In the absence of disturbance, an evolution may be hypothesized towards Quercetalia pubescenti-petraeae communities.Les zones humides côtières d'eau douce sont très rare en Italie. La végétation de l'une d'entre elles a été étudiée selon la méthode de Braun-Blanquet. A l'exception de 1'association Cyperetum flavescentis, déterminée par le piétinement, la vegetation observée peut etre subdivisée en deux groupes : la végétation psammophytique dans les zones les plus élevées (Bromo tectorum-Phleetum arenarii, Schoeneto-Chrysopogonetum grylli), et la végétation hygrophytique dans les dépressions interdunaires (Phragmitetum australis, groupement à Eleocharis uniglumis, groupement à Juncus subnodulosus, Allio suaveolentis-Molinietum) . La corrélation des groupements végétaux avec les valeurs indicatrices de Landolt et resp. avec les éléments chronologiques a été étudiée à l'aide de 1'analyse numérique. La tendance dynamique principale consiste en une série linéaire, car les roselières peuvent évoluer vers l'ordre Molinietalia et ensuite probablement vers l'ordre Populetalia albae. L'association Bromo-Phleetum arenarii peut être considérée comme un gnoupement permanent, conditionnée par des causes soit naturelles soit anthropiques. En 1'absence de perturbation liée à l'érosion, on peut supposer une évolution vers l'ordre Quercetalia pubescenti-petaeae.Piccoli Filippo, Merloni Nicola. Vegetation dynamics in coastal wetlands. An example in Northern Italy : the Bardello. In: Ecologia mediterranea, tome 15 n°1-2, 1989. pp. 81-95

The vegetation of the Comacchio Saltern (Northern Adriatic coast, Italy)

The vegetation of the Comacchio Saltern was studied with the phytosociological method and the data processed with numerical methods. In this biotope, whose activity of salt production was terminated in 1984, seven associations have been found, some having marked phytogeographic interest, namely Pucinellio convolutae -Arthrocnemetum glauci with the subassociations typicum and halocnemetosum strobilacei. The main ecological factors which determine the various distributions of the vegetational types are the level and salinity of the water.La végétation de la Saline de Comacchio a été étudiée selon la méthode de Braun-Blanquet. Les relevés ont été classés par des méthodes d’analyse numérique. Dans ce biotope dont la production du sel a été arrêtée en 1984, 7 associations ont été mises en évidence, quelques-unes entre elles très intéressantes au point de vue phytogéographique et en particulier Puccinellio convolutae -Arthrocnemetum glauci subass. typicum et halocnemetosum strobilacei. Les principaux facteurs écologiques qui déterminent la distribution des types de végétation sont le niveau et la salinité de l’eau.Piccoli Filippo, Merloni Nicola, Pellizzari Mauro. The vegetation of the Comacchio Saltern (Northern Adriatic coast, Italy). In: Ecologia mediterranea, tome 20 n°3-4, 1994. pp. 85-94

Tailored therapy in patients treated with fluoropyrimidines: focus on the role of dihydropyrimidine dehydrogenase

Fluoropyrimidines are widely used in the treatment of solid tumors, mainly gastrointestinal, head and neck and breast cancer. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for catabolism of 5-FU and it is encoded by DPYD gene. To date, many known polymorphisms cause DPD deficiency and subsequent increase of 5-FU toxicity. In addition, reduced inactivation of 5-FU could lead to increased 5-FU intracellular concentration and augmented efficacy of this drugs. Therefore DPD expression, particularly intratumoral, has been investigated as predictive and prognostic marker in 5-FU treated patients. There also seems to be a tendency to support the correlation between DPD expression and response/survival in patients treated with fluoropyrimidine even if definitive conclusions cannot be drawn considering that some studies are conflicting. Therefore, the debate on intratumoral DPD expression as a potential predictor and prognostic marker in patients treated with fluoropyrimidines is still open. Four DPD-polymorphisms are the most relevant for their frequency in population and clinical relevance. Many studies demonstrate that treating a carrier of one of these polymorphisms with a full dose of fluoropyrimidine can expose patient to a severe, even life-threatening, toxicity. Severe toxicity is reduced if this kind of patients received a dose-adjustment after being genotyped. CPIC (Clinical Pharmacogenetics Implementation Consortium) is an International Consortium creating guidelines for facilitating use of pharmacogenetic tests for patient care and helps clinicians ensuring a safer drug delivery to the patient. Using predictive DPD deficiency tests in patients receiving 5FU-based chemotherapy, in particular for colorectal cancer, has proven to be a cost-effective strategy

Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy

The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice

Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy

The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice

Old but gold: the role of drug combinations in improving response to immune check-point inhibitors in thoracic malignancies beyond NSCLC

none8siThe introduction of immune checkpoint inhibitors (ICIs) in non-oncogene addicted non-small cell lung cancer (NSCLC) has revolutionized the treatment scenario and led to a meaningful improvement in patient prognosis. Disappointingly, the success of ICI therapy in NSCLC has not been fully replicated in other thoracic malignancies as small cell lung cancer (SCLC), malignant pleural mesothelioma (MPM), and thymic epithelial tumors (TETs), due to the peculiar biological features of these disease and to the difficulties in the conduction of well-designed, biomarker-driven clinical trials. Therefore, combination strategies of ICIs plus conventional therapies (either chemotherapy, alternative ICIs or targeted agents) have been implemented. Although first approvals of ICI therapy have been recently granted in SCLC and MPM (in combination with chemotherapy and different ICIs), results remain somewhat modest and limited to a small proportion of patients. This work reviews the trial results of ICI therapy in mesothelioma, SCLC, and TETs and discusses the potential of combining ICIs with old drugsrestrictedCantini, Luca; Pecci, Federica; Merloni, Filippo; Lanese, Andrea; Lenci, Edoardo; Paoloni, Francesco; Aerts, Joachim G.J.V.; Berardi, RossanaCantini, Luca; Pecci, Federica; Merloni, Filippo; Lanese, Andrea; Lenci, Edoardo; Paoloni, Francesco; Aerts, Joachim G. J. V.; Berardi, Rossan

Long‑responders to anti‑HER2 therapies: A case report and review of the literature

Since the introduction of targeted therapies, prognosis in human epidermal growth factor receptor (HER) 2-positive metastatic breast cancer (MBC) has radically changed. The addition of Pertuzumab to Trastuzumab and standard chemotherapy has further increased patients' overall survival (OS). However, there is no agreement regarding the optimal duration of trastuzumab therapy in selected patients achieving long-term complete remission. In addition, no potential factors of long-term benefit have been identified yet. In the present study, we report the case of a MBC woman who was successfully treated with trastuzumab for over 10 years. At the time of diagnosis (February 2005), she revealed lung, nodal and bone metastases. Therefore, a first-line chemotherapy with Epirubicine and Docetaxel was administered for 6 cycles and then the patient started Trastuzumab plus hormonal therapy until reaching a sensible reduction of mammary lump and disappearance of distant metastases. Following a multidisciplinary evaluation, in November 2006, the patient underwent radical mastectomy and axillary dissection, achieving a complete remission. She continued Trastuzumab until September 2015 (for a total of 156 cycles) when a pleural diffusion was demonstrated. Long-term survival during anti-HER2 treatment remains a rare and optimal situation. Currently, no data exist to support trastuzumab interruption in this setting and collaborative efforts to better analyze the characteristics of long-responder patients are needed. Data regarding prognostic factors in this setting are relatively confusing. Our review reveals that hormonal receptor (HR)-positive disease is associated with a better prognosis, whereas the role of visceral spread differs by single or dual target anti HER2-inhibition. The introduction of Pertuzumab is raising concerns in terms of toxicity and its cost effectiveness. While waiting for novel molecular data and randomized trials, available evidence advocates continuous use of anti-HER2 therapies until disease progression or development of side effects

Prognostic Impact of Ki-67 Change in Locally Advanced and Early Breast Cancer after Neoadjuvant Chemotherapy: A Single Institution Experience

Systemic neoadjuvant chemotherapy (NCT) is a standard treatment for locally advanced breast cancer (LABC) and for selected early breast cancer (EBC). In these settings, the prognostic and predictive role of Ki-67 before and after NCT is unclear. The aim of our study was to investigate the prognostic role of Ki-67 change in patients not achieving pathological complete response (pCR). We retrospectively analyzed data of patients who did not achieve pCR assessing Ki-67 expression pre- and post-NCT. We stratified three groups: high reduction (>20%), low reduction (1–20%), and no reduction in Ki-67. These groups were correlated with clinical and pathological data by χ2 test. We estimated disease-free survival (DFS) and overall survival (OS) using Kaplan–Meier method, and we adopted univariate and multivariate Cox proportional hazard models. We selected 82 patients from a database of 143 patients, excluding those who were metastatic at diagnosis, achieved pCR, or lack data regarding Ki-67. Median age at diagnosis was 54 years (range 30–75); 51 patients were Luminal B, 10 human epidermal growth factor receptor 2 (HER-2) enriched, and 21 triple negative. A significant correlation between high Ki-67 reduction and luminal B HER-2-negative subtype was observed (p=0,0035). The change in Ki-67 was significantly associated with DFS (p=0,0596) and OS (p=0,0120), also at multivariate analysis (p=0,0256 for DFS; p=0,0093 for OS). In particular, as compared to patients with low/no reduction of Ki-67, those with high Ki-67 reduction (>20%) after NCT showed better survival (60% vs. 56% vs. 83% after 5 years from diagnosis, respectively; p=0.01). In conclusion, in our study, Ki-67 change showed a significant prognostic role in breast cancer patients treated with NCT who did not achieve pCR. Crucially, Ki-67 < 20% identifies a high-risk population that may be eligible for clinical trials with novel therapeutic interventions in adjuvant setting