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The inflammatory potential of the diet decreased significantly after one-year of nutrition counselling on the Mediterranean diet and low glycemic index in women with breast cancer living in Italy.

Immune cell components are able to infiltrate tumor tissues, and different reports described the presence of infiltrating immune cells (TILs) in several types of solid tumors, including breast cancer. The primary immune cell component cells are reported as a lymphocyte population mainly comprising the cytotoxic (CD8+) T cells, with varying proportions of helper (CD4+) T cells and CD19+ B cells, and rarely NK cells. In clinical practice, an expert pathologist commonly detects TILs areas in hematoxylin and eosin (H&E)-stained histological slides via light microscopy. Moreover, other more in-depth approaches could be used to better define the immunological component associated with tumor tissues. Using a multiparametric flow cytometry approach, we have studied the immune cells obtained from breast tumor tissues compared to benign breast pathologies. A detailed evaluation of immune cell components was performed on 15 and 14 biopsies obtained from breast cancer and fibroadenoma subjects, respectively. The percentage of tumor-infiltrating T lymphocytes was significantly higher in breast cancer patients compared to patients with fibroadenoma. Infiltrating helper T lymphocytes were increased in the case of malignant breast lesions, while cytotoxic T lymphocytes disclosed an opposite trend. In addition, our data suggest that the synergistic effect of the presence/activation of NK cells and NKT cells, in line with the data in the literature, determines the dampening of the immune response. Moreover, the lymphocyte-to-monocyte ratio was calculated and was completely altered in patients with breast cancer. Our approach could be a potent prognostic factor to be used in diagnostic/therapeutic purposes for the improvement of breast cancer patients’ management.

Healthy lifestyles are associated with better health-related quality of life (HRQoL), favorable prognosis and lower mortality in breast cancer (BC) survivors. We investigated changes in HRQoL after a 12-month lifestyle modification program in 227 BC survivors participating in DEDiCa trial (Mediterranean diet, exercise, vitamin D). HRQoL was evaluated through validated questionnaires: EQ-5D-3L, EORTC-QLQ-C30 and EORTC QLQ-BR23. Baseline changes were tested using analysis of variance. Multiple regression analyses were performed to assess treatment effects on HRQoL. Increases were observed in global health status (p &lt, 0.001), physical (p = 0.003), role (p = 0.002) and social functioning (p &lt, 0.001), body image (p &lt, 0.001), future perspective (p &lt, 0.001), well-being (p = 0.001), and reductions in fatigue (p &lt, 0.001), nausea and vomiting (p = 0.015), dyspnea (p = 0.001), constipation (p = 0.049), financial problems (p = 0.012), sexual functioning (p = 0.025), systematic therapy side effects (p &lt, 0.001) and breast symptoms (p = 0.004). Multiple regression analyses found inverse associations between changes in BMI and global health status (p = 0.048) and between serum 25(OH)D levels and breast symptoms (p = 0.002). A healthy lifestyle treatment of traditional Mediterranean diet and exercise may impact positively on HRQoL in BC survivors possibly through reductions in body weight while vitamin D sufficiency may improve BC-related symptoms. These findings are relevant to BC survivors whose lower HRQoL negatively affects treatment compliance and disease outcomes.

International audience; The molecular complexity of human breast cancer (BC) renders the clinical management of the disease challenging. Long non-coding RNAs (lncRNAs) are promising biomarkers for BC patient stratification, early detection, and disease monitoring. Here, we identified the involvement of the long intergenic non-coding RNA 01087 (LINC01087) in breast oncogenesis. LINC01087 appeared significantly downregulated in triple-negative BCs (TNBCs) and upregulated in the luminal BC subtypes in comparison to mammary samples from cancer-free women and matched normal cancer pairs. Interestingly, deregulation of LINC01087 allowed to accurately distinguish between luminal and TNBC specimens, independently of the clinicopathological parameters, and of the histological and TP53 or BRCA1/2 mutational status. Moreover, increased expression of LINC01087 predicted a better prognosis in luminal BCs, while TNBC tumors that harbored lower levels of LINC01087 were associated with reduced relapse-free survival. Furthermore, bioinformatics analyses were performed on TNBC and luminal BC samples and suggested that the putative tumor suppressor activity of LINC01087 may rely on interferences with pathways involved in cell survival, proliferation, adhesion, invasion, inflammation and drug sensitivity. Altogether, these data suggest that the assessment of LINC01087 deregulation could represent a novel, specific and promising biomarker not only for the diagnosis and prognosis of luminal BC subtypes and TNBCs, but also as a predictive biomarker of pharmacological interventions.

Background The molecular complexity of human breast cancer (BC) is one of the current challenges for the clinical management of the disease. The identification of subtype-specific biomarkers, such as long non-coding RNAs (lncRNAs), is currently investigated to improve BC patient’s stratification, early detection and disease monitoring. Methods High-throughput sequencing approach of rRNA-depleted RNA samples extracted from 61 laser-microdissected breast tissues, supported by in silico analyses relying on TCGA database (n = 813), were performed to define a specific signature of lncRNAs in the different BC subtypes. Focusing on the long intergenic non-coding RNA 01087 (LINC01087), we estimated its prognostic value using Kaplan-Meier Plotter Database, together with its association with clinical parameters and the histological tumor type within the TCGA cohort of BC patients. cBioPortal data were used to evaluate the expression level of LINC01087 according to the mutational status of TP53, BRCA1 and BRCA2 in BC patients. TCGA samples of triple-negative BC (TNBC) and luminal BCs have been segregated according to the expression level of LINC01087 for comparative analysis of the transcriptomic profiles to identify genes modulated upon variation of the level of LINC01087. GO, KEGG and REACTOME functional annotation and enrichment analyses of these modulated genes were conducted, and their protein-protein interaction networks built using STRING database. Results We identified the involvement of LINC01087 in breast oncogenesis. LINC01087 appeared significantly downregulated in TNBCs and upregulated in the luminal BC subtypes in comparison to mammary samples from cancer-free woman and matched normal cancer tissue pairs. Deregulation of LINC01087 allowed to accurately distinguish luminal and TNBC specimens, independently of the clinicopathological parameters, of the histological and TP53 or BRCA1/2 mutational status. Moreover, a higher level of LINC01087 expression predicted a better prognosis in luminal BCs, while TNBCs harboring a lower expression of LINC01087 were associated with a reduced relapse-free survival. Furthermore, bioinformatics analyses suggested a putative tumor suppressor activity of LINC01087 through interference with pathways involved in cell survival, proliferation, adhesion, or inflammation. Conclusions The assessment of LINC01087 deregulation in BCs represents a novel and specific biomarker for the diagnosis of luminal BC and TNBC subtypes, and also to predict their clinical outcome.

Evidence suggests a beneficial role of the Mediterranean Diet (MedDiet) on health-related quality of life (HRQoL) in healthy subjects. HRQoL is relevant in cancer therapy and disease outcomes, therefore we investigated the association between adherence to the MedDiet and HRQoL in breast cancer survivors participating in the multicentre trial DEDiCa. Diet and HRQoL were assessed at baseline in a subgroup of 309 women enrolled within 12 months of breast cancer diagnosis without metastasis (stages I-III, mean age 52±1 yrs, BMI 27±7 kg/m2). The 14-item PREDIMED questionnaire was used to analyse adherence to the MedDiet. HRQoL was assessed with three validated questionnaires measuring physical, mental, emotional and social factors: EQ-5D-3L, EORTC QLQ-C30 and EORTC QLQ-BR23. Analysis of variance (ANOVA) and multivariate analyses were performed to assess the possible role of the MedDiet on HRQoL. Patients with higher adherence to MedDiet (PREDIMED score >7) showed significantly higher scores for physical functioning (p = 0.02) and lower scores on the symptomatic pain scale (p = 0.04) assessed by the EORTC QLQ-C30 questionnaire compared to patients with a lower adherence to MedDiet (PREDIMED score ≤7). Higher scores from the EQ-5D-3L indicating higher well-being were observed mainly in participants with higher MedDiet adherence (p = 0.05). In adjusted multivariate analyses significant positive associations were found between MedDiet, physical functioning (p = 0.001) and EQ 5D-3L score (p = 0.003) while inverse associations were found with pain and insomnia symptoms (p = 0.005 and p = 0.029, respectively). These results suggest that higher adherence to the MedDiet in breast cancer survivors is associated with better aspects of quality of life, specifically higher physical functioning, better sleep, lower pain and generally higher well-being confirming findings in healthy subjects.

One-stage implant-based breast reconstruction using titanium-coated polypropylene mesh is a novel approach widely used in Europe. Complication rates in breast reconstruction with the use of titanium-coated meshes seem to be comparable to those in patients with implant-based breast reconstruction alone. However, the use of synthetic meshes in implant-based breast reconstructive surgery leads to new clinical scenarios with the need for the breast surgeon to face new complications. We present an innovative treatment of implant exposure in the absence of infection in patients who underwent nipple-sparing mastectomy and immediate breast reconstruction with silicone implants and titanium-coated polypropylene mesh by using a pedicled sub-mammary intercostal perforator flap. Four patients who experienced implant exposure without infection have been treated with the use of a sub-mammary intercostal perforator flap. Whole coverage of the exposed implant/mesh with a sub-mammary intercostal perforator flap was obtained in all cases. No post-operative complications have been observed, whereas a pleasant aesthetic result has been achieved. Patients’ post-operative quality of life and satisfaction levels were measured by the European Organisation for Research and Treatment of Cancer breast cancer-specific quality of life QLQ-BR23 questionnaire and showed an average good satisfaction with the post-operative outcomes (mean QLQ-BR23 score 1.9). For the first time, a sub-mammary intercostal perforator flap has been used with the aim of treating implant exposures without removing the prosthesis even in the presence of synthetic meshes, when wound infection was excluded. Although tested on a small series, the sub-mammary intercostal perforator flap might represent a simple, versatile and cost-effective procedure for the management of implant exposure following nipple-sparing mastectomy and immediate reconstruction with silicone implants and synthetic meshes. It should be considered to avoid implant removal followed by delayed free flap reconstruction as “salvage surgery.” This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background Breast cancer is the most common malignancy amongst elderly women. It represents the main cause of mortality for those women and it is steadily increasing. The primary therapeutic approach remains surgery, as in other age groups. The role of radiotherapy following surgery is still debated. The use of hypofractionated schedules is challenging the standard fractionation and has now been considered an advantageous option within this subgroup of patients. Results from randomized controlled trials have not been shown to be inferior to standard fractionation in terms of local recurrence, disease-free survival and overall survival. Acute and late side effects were not increased by hypofractionated regimens. Patients and methods 60 elderly women treated by hypofractionated radiotherapy after breast conserving surgery were stratified by age. Comorbidities associated compliance and toxicity correlation to age were the first endpoints of the study. Comorbidity associated compliance was calculated by Cumulative Illness Rating Scale Geriatric. Results At a median follow-up of 15 months overall survival was 100%, without severe late toxicity. No statistical significant differences were found between Cumulative Illness Rating Scale-Geriatric, systemic therapy and toxicity. Conclusion In our experience hypofractioned regimens seem to be safe and reliable in the elderly setting, although longer follow up is needed.

By analyzing multiple gene panels, next-generation sequencing is more effective than conventional procedures in identifying disease-related mutations that are useful for clinical decision-making. Here, we aimed to test the efficacy of an 84 genes customized-panel in BRCA1 and BRCA2 mutation-negative patients. Twenty-four patients were enrolled in this study. DNA libraries were prepared using a picodroplet PCR-based approach and sequenced with the MiSeq System. Highly putative pathogenic mutations were identified in genes other than the commonly tested BRCA1/2: 2 pathogenic mutations one in TP53 and one in MUTYH; 2 missense variants in MSH6 and ATM, respectively; 2 frameshift variants in KLLN, and ATAD2, respectively; an intronic variant in ANPEP, and 3 not functionally known variants (a frameshift variant in ATM a nonsense variant in ATM and a missense variant in NFE2L2). Our results show that this molecular screening will increase diagnostic sensitivity leading to a better risk assessment in breast cancer patients and their families. This strategy could also reveal genes that have a higher penetrance for breast and ovarian cancers by matching gene mutation with familial and clinical data, thereby increasing information about hereditary breast and ovarian cancer genetics and improving cancer prevention measures or therapeutic approaches.

The so called “Triple Negative Breast Cancer” (TNBC) represents approximately 15-20% of breast cancers. This acronym simply means that the tumour does not express oestrogen receptor (ER) and progesterone receptor (PR) and does not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene. Despite this unambiguous definition, TNBCs are an heterogeneous group of tumours with just one common clinical feature: a distinctly aggressive nature with higher rates of relapse and shorter overall survival in the metastatic setting compared with other subtypes of breast cancer. Because of the absence of well-defined molecular targets, cytotoxic chemotherapy is currently the only treatment option for TNBC. In the last decades, the use of more aggressive chemotherapy has produced a clear improvement of the prognosis in women with TNBC, but this approach results in an unacceptable deterioration in the quality of life, also if some support therapies try to relieve patients from distress. In addition, there is the general belief that it is impossible to further improve the prognosis of TNBC patients with chemotherapy alone. In view of that, there is a feverish search for new “clever drugs” able both to rescue chemo-resistant, and to reduce the burden of chemotherapy in chemo-responsive TNBC patients. A major obstacle to identifying actionable targets in TNBC is the vast disease heterogeneity both inter-tumour and intra-tumour and years of study have failed to demonstrate a single unifying alteration that is targetable in TNBC. TNBC is considered the subtype that best benefits from the neoadjuvant model, since the strong correlation between pathological Complete Response and long-term Disease-Free-Survival in these patients. In this review, we discuss the recent discoveries that have furthered our understanding of TNBC, with a focus on the subtyping of TNBC. We also explore the implications of these discoveries for future treatments and highlight the need for a completely different type of clinical trials.

Qualitative assessment of un- certain (type II) time-intensity curves (TICs) in breast DCE-MRI is problematic and operator dependent. The aim of this work is to evaluate if a semi-quanti- tative assessment of uncertain TICs could improve overall diagnostic performance. Methods: In this study 49 lesions from 44 patients were retrospectively analysed. Per each lesion one region-of-interest (ROI)- averaged TIC was qualitatively evaluated by two ra- diologists in consensus: all the ROIs resulted in type II (uncertain) TIC. The same TICs were semi-quan- titatively re-classified on the basis of the difference between the signal intensities of the last-time-point and of the peak: this difference was classified accord- ing to two different cut-off ranges (±5% and ±3%). All patients were cytological or histological biopsy proven. Fisher test and McNemar test were per- formed to evaluate if results were statistically signifi- cant (p < 0.05). Results: Using ±5% cut-off 16 TICs were reclassified as type III and 12 as type I while 21 were reclassified again as type II. Using ±3% 22 TICs were reclassified as type III and 16 as type I while 11 were reclassified again as type II. The semi-quantita- tive classification was compared to the histological- cytological results: the sensitivity, specificity, positive and negative predictive values obtained with ±3% were 77%, 91%, 91% and 78% respectively while using ±5% were 58%, 96%, 94% and 68% respec- tively. Using the ±5% cut-off 26/28 (93%) TICs were correctly reclassified while using the ±3% cut-off 34/38 (90%) TICs were correctly reclassified (p < 0.05). Conclusions: Semi-quantitative methods in ki- netic curve assessment on DCE-MRI could improve classification of qualitatively uncertain TICs, leading to a more accurate classification of suspicious breast lesions.

Breast cancer is considered the most common cancer for women worldwide and it is now the second leading cause of cancer-related deaths among females in the world. Since breast cancer is highly resistant to chemotherapy, alternative anticancer strategies have been developed. In particular, many studies have demonstrated that curcumin, a derivative of turmeric, can be used as natural agent in treatment of some types of cancer by playing antiproliferative and antioxidant effects. In our study, we assessed the antitumor activities of curcumin in ER-negative human breast cancer cell line resistant to chemotherapy, MDA.MB231 byin vitroandin vivoexperiments.In vitrodata allowed us to demonstrate that curcumin played a role in regulation of proliferation and apoptosis in MDA.MB231 cells.In vivo, by generation of mouse model of breast cancer, we showed that treatment of curcumin inhibited tumor growth and angiogenesis. Specifically, we showed that curcumin is able to deregulate the expression of cyclin D1, PECAM-1, and p65, which are regulated by NF-κB. Our data demonstrated that curcumin could be used as an adjuvant agent to chemotherapy in treatment of triple negative breast cancer.

// Giuseppe Buono 1, * , Anna Crispo 2, * , Mario Giuliano 1, 3 , Carmine De Angelis 1 , Francesco Schettini 1 , Valeria Forestieri 1 , Rossella Lauria 1 , Matilde Pensabene 1 , Michelino De Laurentiis 4 , Livia Silvia Adriana Augustin 2, 5 , Alfonso Amore 4 , Massimiliano D’Aiuto 4 , Raffaele Tortoriello 4 , Antonello Accurso 6 , Ernesta Cavalcanti 2 , Gerardo Botti 2 , Maurizio Montella 2 , Sabino De Placido 1 and Grazia Arpino 1 1 Department of Clinical Medicine and Surgery, Oncology Division, University of Naples Federico II, Naples, Italy 2 Unit of Epidemiology, National Cancer Institute, G. Pascale Foundation, Naples, Italy 3 Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA 4 Breast Unit, National Cancer Institute, G. Pascale Foundation, Naples, Italy 5 Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital, Toronto, Canada 6 Department of Gastroenterology, Endocrinology and Surgery, University of Naples Federico II, Naples, Italy * These authors contributed equally to this work Correspondence to: Grazia Arpino, email: grazia.arpino@unina.it Keywords: breast cancer; obesity; diabetes; combined variables; outcome Received: August 19, 2017 Accepted: November 16, 2017 Published: December 05, 2017 ABSTRACT Background: Previous studies suggested that obesity and diabetes were correlated with breast cancer outcome. The aim of the present study was to investigate the prognostic effect of obesity and diabetes on the outcome of early breast cancer patients. Materials and Methods: Overall, 841 early breast cancer patients were prospectively enrolled between January 2009 and December 2013. Study population was divided into four groups: (1) patients without obesity or diabetes; (2) patients with only diabetes; (3) patients with only obesity; and (4) patients with both diabetes and obesity. Categorical variables were analyzed by the chi-square test and survival data by the log-rank test. Results: At diagnosis, obese and diabetic patients were more likely to be older ( p < 0.0001) and post-menopausal ( p < 0.0001) and to have a tumor larger than 2 cm ( p < 0.0001) than patients in groups 1–3. At univariate analyses, obese and diabetic patients had a worse disease-free survival ( p = 0.01) and overall survival ( p = 0.001) than did patients without obesity and diabetes. At multivariate analyses, the co-presence of obesity and diabetes was an independent prognostic factor for disease-free survival (hazard ratio=2.62, 95% CI 1.23–5.60) but not for overall survival. Conclusions: At diagnosis, patients with obesity and diabetes were older, had larger tumors and a worse outcome compared to patients without obesity or diabetes. These data suggest that metabolic health influences the prognosis of patients affected by early breast cancer.

Adenoma of the nipple (AN) represents a rare benign mammary proliferation of lactiferous ducts. It appears as an erosive or ulcerative lesion, which in a number of cases is associated with a serous/hematic secretion. AN may be clinically confused with Paget's disease and histologically with invasive breast carcinoma or breast cancer precursor lesions. Therefore, the histological and immunophenotypic analysis is essential for the differential diagnosis. The present study describes the histopathological characteristics of a first case series of AN.

Bone metastases are a frequent complication of advanced oncologic disease. Pain associated to bone metastasis is a major cause of morbidity in cancer patients, especially in elderly. The aim of this multicentric retrospective observational study is to evaluate the efficacy of different schedules of radiation therapy in elderly patients in terms of pain relief. 206 patients over the age of 60 were enrolled in 1 year time for a multicentre retrospective observational study. Patients were treated with palliative purposes for painful bone metastases. Pain intensity difference (PID) was found in 72% of patients. Reported PID was statistically significant for p

Background Mechanisms influencing breast cancer (BC) development and recurrence include hyperglycemia, hyperinsulinemia, high insulin-like growth factor-1, high circulating estrogen, inflammation and impaired cellular differentiation/apoptosis. A lifestyle program that targets all the above mechanisms may be warranted. Low glycemic index (GI) foods produce lower post-prandial glucose and insulin responses and have been associated with lower BC risk. Moderate physical activity post-diagnosis reduces BC recurrence and mortality, partly explained by reduced insulin and estrogen levels. Vitamin D increases cell differentiation/apoptosis and high serum vitamin D levels improve BC survival. Yet no trial has evaluated the combined effect of a low GI diet, moderate physical activity and vitamin D supplementation on BC recurrence in the context of a Mediterranean lifestyle setting. Methods Women (30-74 yr) who had undergone surgery for primary histologically confirmed BC (stages I-III) within the previous 12 months, in cancer centres in Italy, will be randomized to follow, for a maximum of 33 months, either a high intensity treatment (HIT) composed of low GI diet + exercise + vitamin D (60 ng/mL serum concentration) or a lower intensity treatment (LITE) with general advice to follow a healthy diet and exercise pattern + vitamin D to avoid insufficiency. Both interventions are on a background of a Mediterranean diet. Considering a 20% recurrence rate within 3 years for BC cases and a predicted rate of 10% in the HIT group, with power of 80% and two-sided alpha of 0.05, the subject number required will be 506 (n = 253 in each arm). Clinic visits will be scheduled every 3 months. Dietary and exercise counselling and vitamin D supplements will be given at each clinic visit when blood samples, anthropometric measures and 7-day food records will be collected. Discussion DEDiCa study aims to reduce BC recurrence in women with BC using a lifestyle approach with additional vitamin D and to investigate possible cardio-metabolic benefits as well as epigenetic modifications according to lifestyle changes. Given the supporting evidence and safety of the components of our intervention we believe it is feasible and urgent to test it in cancer patients. Trial registration May 11, 2016; NCT02786875. EudraCT Number 2015-005147-14

About 10% of all breast cancers arise from hereditary mutations that increase the risk of breast and ovarian cancers; and about 25% of these are associated with the BRCA1 or BRCA2 genes. The identification of BRCA1/BRCA2 mutations can enable physicians to better tailor the clinical management of patients; and to initiate preventive measures in healthy carriers. The pathophysiological significance of newly identified variants poses challenges for genetic counseling. We characterized a new BRCA1 variant discovered in a breast cancer patient during BRCA1/2 screening by next-generation sequencing. Bioinformatic predictions; indicating that the variant is probably pathogenetic; were verified using retro-transcription of the patient's RNA followed by PCR amplifications performed on the resulting cDNA. The variant causes the loss of a canonic donor splice site at position +2 in BRCA1 intron 21; and consequently the partial retention of 156 bp of intron 21 in the patient's transcript; which demonstrates that this novel BRCA1 mutation plays a pathogenetic role in breast cancer. These findings enabled us to initiate appropriate counseling and to tailor the clinical management of this family. Lastly; these data reinforce the importance of studying the effects of sequence variants at the RNA level to verify their potential role in disease onset.

The aim of this study was to assess the response to cytotoxic and hormone neo-adjuvant chemotherapy in four patients with locally advanced breast cancer by simultaneous PET/MRI. Four patients with locally advanced breast cancer underwent simultaneous PET/MRI of the breast using a 3 T Biograph mMR before and after neo-adjuvant chemotherapy (two patients were treated with hormone-therapy and two patients were treated with cytotoxic chemotherapy). Morpho-structural tumoral features and tumor size were assessed; area value, metabolic (SUV and MTV) and functional (ADC, K trans, V e, k ep and iAUC) data were obtained by positioning regions of interest. A comparison of all parameters between the pre- and post-treatment PET/MRI examinations and between the two different therapeutic schedules was assessed. In patients treated with cytotoxic chemotherapy and classified as PR, there was a significant reduction of post-treatment morphological, metabolic and functional parameters. In a patient treated with hormone therapy, classified as SD, there was an increase of all post-treatment perfusion parameters, a substantially stable ADC value and a poor reduction of lesion size and of maximum SUV (SUVmax) values; the last patient, treated with hormone therapy and classified as PR, showed a significant reduction of lesion size and SUVmax values with a reduction of perfusion parameters and substantially stable ADC values. Multiparametric evaluation with simultaneous PET/MRI could be a useful tool to assess the response to cytotoxic and hormone neo-adjuvant chemotherapy in patients with breast cancer. Future studies in a larger cohort of patients are warranted to confirm the results of this preliminary study.

Background Breast cancer is the most common malignancy amongst elderly women and the main cause of mortality. A specific management for elderly woman is not clear because clinical trials are usually not customized for this subset of patients. Aims The aim of this paper is to provide an overview of the available information on the main issues in the field of breast cancer radiotherapy in the elderly population. Materials and methods Authors discuss on different radiation treatments for breast cancer in the elderly, based on the data of the literature with a focus on new strategy: hypo-fractionation, accelerated partial breast irradiation, and the utility of a dose boost. Discussion The treatment of breast cancer is not standardized in the elderly. The optimal management in this population often requires complex multidisciplinary supportive care due to multiple comorbidities to optimize their cancer care. Conclusions New options such as APBI or HyRT regimens should be taken into consideration and offered as a breach of duty to the elderly population. Furthermore, they should be extensively investigated through randomized clinical trials.

Purpose To obtain breast vascular map and to assess correlation between predominant feeding vessel and tumor location with a semi-automatic method compared to conventional radiologic reading. Methods 148 malignant and 75 benign breast lesions were included. All patients underwent bilateral MR imaging. Written informed consent was obtained from the patients before MRI. The local ethics committee granted approval for this study. Semi-automatic breast vascular map and predominant vessel detection was performed on MRI, for each patient. Semi-automatic detection (depending on grey levels threshold manually chosen by radiologist) was compared with results of two expert radiologists; inter-observer variability and reliability of semi-automatic approach were assessed. Results Anatomic analysis of breast lesions revealed that 20% of patients had masses in internal half, 50% in external half and the 30% in subareolar/central area. As regards the 44 tumors in internal half, based on radiologic consensus, 40 demonstrated a predominant feeding vessel (61% were supplied by internal thoracic vessels, 14% by lateral thoracic vessels, 16% by both thoracic vessels and 9% had no predominant feeding vessel—p

Introduction The purpose of this study was to evaluate the added value of breast magnetic resonance imaging (MRI) in preoperative diagnosis of ductal carcinoma in situ (DCIS). We reviewed our institution database of 3499 consecutive patients treated for breast cancer. Patients and Methods A total of 362 patients with histologically proven DCIS were selected from the institutional database. Of these, 245 (67.7%) preoperatively underwent conventional imaging (CI) (mammography/ultrasonography) (CI group), and 117 (32.3%) underwent CI and dynamic MRI (CI + MRI group). The pathology of surgical specimens served as a reference standard. The Mann-Whitney U , χ 2 test, and Spearman correlation coefficient were performed. Results The CI + MRI group showed a sensitivity of 98.5% with an increase of 10.1% compared with the CI group to detect pure DCIS. Dynamic MRI identified 19.7% (n = 13) additional pure DCIS compared with CI. In the CI + MRI group, a single (1.5%) false negative was reported, whereas in the CI group, 11 (11.6%) false negatives were reported. Moreover, the CI + MRI group showed a sensitivity of 98.0% to detect DCIS + small invasive component. In this group, dynamic MRI identified 21.6% (n = 11) additional DCIS and a single (2.0%) false negative compared with the CI group, whereas in the CI group, 7 (4.7%) false negatives were reported. MRI and histopathologically measured lesion sizes, Breast Imaging Reporting and Data System MRI assessment categories, and enhancement signal intensity curve types showed a significant correlation. The MRI detection rate of DCIS increased significantly with increasing nuclear grade. Conclusions Preoperative breast MRI showed a better accuracy then CI in preoperative diagnosis for both pure DCIS and DCIS + small invasive component with a precise assessment of lesion size. This can provide a more appropriate management of DCIS patients.

Introduction Screening and adjuvant postoperative therapies have increased survival amongst women with breast cancer, but these tools are seldom applied in elderly patients. Higher rates of local recurrence occur in those elderly patients who avoid radiotherapy. TARGIT-A and ELIOT trials has been reported to not to be inferior to external beam RT in suitable subgroups of patients. The TARGIT-Elderly trial has been launched in order to confirm the efficacy of intraoperative radiotherapy (IORT) in a well selected group of elderly patients who are more likely to decline radiation treatment. Objectives Current evidence of the medical literature on the clinical reliability and applicability of intraoperative radiotherapy amongst older women diagnosed with early breast cancer is after summarized. Materials and methods Literature databases were searched up to June 2015. Terms used to retrieve articles were ‘breast cancer', ‘elderly', ‘intraoperative radiotherapy', ‘IORT' and ‘IOERT'. Results Elderly patients with pT1N0 tumours are regarded to be suitable for IORT according to ASTRO and GEC-ESTRO recommendations, respectively. Discussion In the light of the medical literature we can assume that patients benefit from postoperative radiation therapy, but we still do not know who can be spared from it. These issues emphasize the urgent need to develop and support clinical trials for this older population of breast cancer patients. Conclusions Whether radiotherapy is beneficial in elderly still remains a matter of debate. IORT along with BCS in a selected subgroup of patients (>70years, pT1N0 tumours) could represent a valid option for a better local control.

Purpose. To determine the diagnostic accuracy of DOBIComfortScan in patients with Breast Imaging Reporting suspect breast lesions (BI-RADS) 4-5 breast lesions. Materials and Methods. One-hundred and thirteen patients underwent DOBIComfortScan examination before surgery. Twelve parameters were taken into consideration to define DOBI findings. Results. Twenty-seven radical mastectomies, 47 quadrantectomies and 39 wide excisions, were performed. Overall, 65 invasive cancer, 9 in situ carcinoma and 39 nonmalignant lesions, were observed. Ten out of 12 considered parameters resulted significantly in association with histology at discriminant analysis. A summation score of 30.5 resulted to be the best cut off at ROC analysis, giving a sensitivity and specificity of 80% and 87%, respectively, and a positive predictive value of 92.2%. Finally the following DOBI-BI-RADS model was developed: malignant B5≥38 score); possibly malignant (B4=25-37 score); benign but the possibility of malignancy cannot be excluded (B3=20-24 score); benign (B2<20 score). Conclusion. definition of other parameters permits to improve the accuracy of this procedure. Further studies are warranted to define the potential role of DOBIComfortScan in breast cancer imaging.

Postmenopausal women show the highest incidence of breast cancer in the female population and are often affected by metabolic syndrome. Metabolic syndrome (MS)--characterized by central adiposity, insulin resistance, low serum high-density lipoprotein cholesterol (HDL-C), high serum triglyceride and high blood pressure--seems to be strictly correlated to breast carcinogenesis. We enrolled 777 healthy women and women with breast cancer in our nested case-control study to evaluate the association between MS and breast cancer, analyzing anthropometric parameters (weight, height, BMI, waist and hip circumference), blood pressure, serum HDL-C, triglyceride, fasting plasma glucose, insulin, testosterone and uric acid levels and administering a questionnaire about physical activity, food intake, tobacco use, alcohol abuse, personal and familial history of disease. We found an higher prevalence of metabolic syndrome (30%) in postmenopausal breast cancer patients compared to healthy women (19%). None of the individual MS features was strong enough to be considered responsible for breast carcinogenesis alone. However, of the 63 postmenopausal breast cancer cases associated to MS, 30% presented three or more MS features, suggesting that the activation of multiple molecular pathways underlying MS might contribute to tumorigenesis. Our data support the hypothesis that MS may be an indicator of breast cancer risk in postmenopausal women. The unsettlement of the hormonal arrangement in postmenopausal, along with an increase in visceral adiposity, probably favour the hormone-dependent cell proliferation, which drives tumorigenesis. Adjustments in lifestyle with physical activity intensification and healthy diet could represent modifiable factors for the primary prevention of sporadic breast cancer.

Cystic breast lesions with a nonsimple appearance, either complicated or complex, pose unique diagnostic difficulties, in part owing to their potentially malignant nature. Current ultrasound classification systems are based on morphostructural aspects only. The objective of this paper is to highlight the adjunctive role of Doppler techniques. Over a 1-year period, we prospectively evaluated 45 women with atypical breast cysts of type IV, V or VI according to the Chang classification. Forty patients were symptomatic, whereas the cyst was discovered as an incidental finding in five cases. Our assessment included morphostructural, angioarchitectural and flowmetric aspects. Twenty-three nontumoural lesions were managed conservatively. All 19 type-IV cysts and all four type-V cysts according to the Chang classification showed absence of signal flow at colour Doppler imaging. Among the 22 tumoural lesions, there were eight papillomas, one atypical ductal hyperplasia and 13 carcinomas. The eight papillomas showed single (four cases) or multiple (four cases) mural projections. The atypical ductal hyperplasia showed a single parietal nodule. Among the 13 carcinomas, patterns included mural projections in 11 cases, eccentric cystic wall thickening in one and coarse intracystic septa in one. Cystic content appeared clear in six papillomas and in the case of atypical ductal hyperplasia, whereas it exhibited fine echoes in two papillomas. Among the carcinomas, cystic content showed coarse echoes in two cases and fine echoes in 11. Intralesional calcifications were seen in three carcinomas. Posterior enhancement was present in all carcinomas, whereas none showed posterior shadowing. In three carcinomas, some small solid satellite nodules were evident. Colour Doppler imaging showed lack of flow in four papillomas and subtle flow in the remaining four papillomas and in the atypical ductal hyperplasia. All 13 carcinomas showed diffuse vascularity, with multiple sparse vessels and multiple vascular poles. The resistive index, measurable in 4/8 papillomas, was 0.43 on average. Spectral analysis was measured in all carcinoma cases, yielding a mean resistive index of 0.71. Intracystic breast tumours exhibit distinctive morphostructural and colour Doppler features that allow effective differentiation from nontumoural cysts. Frequently, a presumptive differentiation between papillomas and carcinomas can be achieved. Absence of flow signals represents an additional criterion for complicated/complex cysts, allowing conservative management. Vascularity indicates the need for excision or biopsy of the solid projections, even in cases with negative cytology.

Purpose To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment Bone Effects study). Patients and Methods Prospectively collected hormonal data were available for 81 premenopausal women, of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin ± zoledronate. Serum 17-β-estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), Δ4-androstenedione, testosterone, dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline and after 6 months of treatment. For each hormone, 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test. Results Median age was 44 years for both groups of patients. Letrozole + triptorelin (± zoledronate) induced a stronger suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median FSH serum levels were suppressed in both groups, but such suppression was lower among patients receiving letrozole, who showed significantly higher median FSH serum levels (P < .0001). No significant differences were observed for testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups of patients. Conclusion Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Large and consistent evidence supports the role of body mass index (BMI) as a prognostic and predictive indicator in breast cancer. However, there is paucity of data specifically referred to women diagnosed at a young age across the different disease settings. We investigated the impact of BMI on treatment outcomes in 86 breast cancer patients aged 45 y or less treated with neoadjuvant chemotherapy (CT) followed by surgery.Pathologic complete response (pCR) was defined as the eradication of cancer from both breast and lymph nodes. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier product-limit method. Curves were compared by long rank test for significance. Potential predictors of survival were tested in Cox models.We observed a pCR in 19 patients (22%). Lower values of BMI were more commonly associated with pCR (p = 0.05). Results from univariate, but not multivariate, models were somewhat supportive of higher pCR rates in leaner women (p = 0.06). None of the variables impacted DFS. OS was longer in leaner patients (medians and 95%CI: 74.6 months, 66.2-82.9 and 58.5 months, 49.6-67.4, p = 0.009). Longer OS was also related to lower T-stage, adjuvant radiotherapy (RT), and non triple negative (TN) subtype (p = 0.046, p = 0.024, and p = 0.015, respectively). Cox models confirmed the protective role of lower BMI (Hazard Ratios: 0.30, 95%CI: 0.12-0.71, p = 0.007), non TN subtype and adjuvant RT (p = 0.008 and p = 0.024).In young breast cancer patients treated with neoadjuvant CT followed by surgery, lower values of BMI are associated with longer OS. Our data also showed longer OS in association with a non TN molecular subtype and adjuvant RT. The modifiable nature of BMI and aggressive biologic behavior of the disease diagnosed at a young age encourage further studies to corroborate our findings.

Virtual reality (VR) during chemotherapy has resulted in an elapsed time compression effect, validating the use of VR in the treatment of some stressful conditions. In the past literature the framework of the pacemaker–accumulator cognitive model of time perception resulted very reliable to explain this effect. This pilot-study explored the efficacy of Virtual Reality in reducing the perception of time during receipt of intravenous chemotherapy. Patient’s retrospective estimates of time elapsed during this treatment were evaluated versus patient’s treated with Music-Therapy. Materials and methods 47 breast cancer patients were randomly assigned to 20 min of VR treatment (N = 24) or 20 min of Music-therapy (N = 23) during chemotherapy infusion. Difference between actual and perceived elapsed time during chemotherapy with VR and with MT were evaluated with ANOVA analysis. Results: The VR group underestimated the time spent with VR treatment, instead MT treatment group overestimated it. In one step anova model, the VR versus MT treatment showed a significant difference in terms of altered time perception (F = 5.06, p = 0.0008). Further analysis on the same panel of patients will be conducted to explain also the role of some possible mediator of this effect.

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. The diagnosis, treatment, and long-term management of cancer can present individuals with a multitude of stressors at various points in that trajectory. Psychosocial distress may appear early in the diagnostic process and have negative effects on compliance with treatment and subsequent quality of life. Purpose. The aim of the study was to determine early-phase predictors of distress before any medical treatment. Method. Consistent with the goals of the study, 123 newly diagnosed breast cancer patients (20 to 74 years old) completed multiple indicators of knowledge about breast cancer management and treatment, attitudes toward cancer, social support, coping efficacy, and distress. Results. SEM analysis confirmed the hypothesized model. Age was negatively associated with the patient's knowledge (β = - 0.22), which, in turn, was positively associated with both attitudes toward breast cancer (β = 0.39) and coping self-efficacy (β = 0.36). Self-efficacy was then directly related to psychological distress (β = - 0.68). Conclusions. These findings establish indicators of distress in patients early in the cancer trajectory. From a practical perspective, our results have implications for screening for distress and for the development of early interventions that may be followed by healthcare professionals to reduce psychological distress.

Purpose: The present study aimed to define the antitumor activity of eight cisplatin – epirubicin – paclitaxel (PET) weekly cycles with granulocyte colony-stimulating factor (G-CSF) support in patients with large operable breast cancer. Methods: Operable breast cancer (T2 –3 N0– 1; T >3 cm) patients received eight preoperative weekly cycles of cisplatin 30 mg/m 2 , epirubicin 50 mg/m 2 and paclitaxel 120 mg/m 2 , with G-CSF (5mg/kg, days 3– 5) support. Results: Sixty-three patients (T2/T3 = 30/33; N0/N + = 8/55) were enrolled. Thirty-one clinical complete (49%) and 30 partial (48%) responses were recorded, giving a 97% response rate (95% confidence interval 89% to 100%). Breast-sparing surgery was performed in 32/63 (51%) patients. At pathological assessment, 28 patients (45%) showed absence of invasive residual disease in breast and 34 (55%) had negative axilla. In 20 women (32%) both breast and axilla were found to be disease-free. At a 23-month median follow-up (range 4 – 63), only eight relapses and two deaths had occurred, with the 4-year projected relapse-free and overall survival being 59% and 95%, respectively. Grade 3 – 4 neutropenia and anemia occurred in 24% and 5% of patients, respectively. Emesis, diarrhea and mucositis were the main non-hematological toxicities; however, only nine (14%) patients experienced one or more episodes of severe non-hematological toxicity. Peripheral neuropathy was frequent, but never severe. Conclusions: A 2-month weekly treatment with PET represents a well tolerated and highly effective approach in large operable breast cancer patients. In spite of the short duration of chemotherapy, one-third of patients achieved a complete eradication of the tumor in both breast and axilla.

Purpose: The present study was aimed at defining the antitumor activity of the cisplatin-epirubicin-paclitaxel (PET) weekly administration with granulocyte colony-stimulating factor (G-CSF) support in chemonaive small-cell lung cancer patients with extensive disease (ED-SCLC). Methods: Chemonaive ED-SCLC patients received cisplatin 30 mg/sqm, epirubicin 50 mg/sqm and paclitaxel 120 mg/sqm, weekly, with G-CSF (5 µg/kg from day 3 to 5) support, for a maximum of 12 weeks. Results: Thirty-nine patients were treated, for a total of 354 cycles delivered. Eight complete (21%), and 22 partial responses (56%) were recorded, giving a 77% (95% CI = 61–89%) objective response rate (ORR). After 14 (range, 7–28)-month median follow-up, 24 deaths have occurred. Median progression-free and overall survival were 7 months and 11 months, with 1- and 2-year projected survivals of 45 and 24%, respectively. No toxic deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 4 (10%) and 1 (3%) patients, respectively. Only one case of neutropenic sepsis was recorded, while hemorrhagic thrombocytopenia was never observed. Emesis, loss of appetite, mucositis and fatigue were the main nonhematological toxicities, being severe in 9, 8, 4 and 7 patients, respectively. Conclusions: The weekly PET combination with G-CSF support represents an active therapeutic approach in chemonaive ED-SCLC patients. However, both ORR and median survival does not seem substantially better than those achievable with a standard regimen. In view of that, and in consideration of the relevant nonhematological toxicity, this approach should not be pursued outside clinical trials.

Purpose: To evaluate the feasibility and activity of combination treatment with docetaxel (DTX) and irinotecan (CPT-11), given together every other week, combined with filgrastim support, in anthracycline- and paclitaxel-pretreated breast cancer (BC) patients. Patients and Methods: Advanced BC patients pretreated with anthracycline- and paclitaxel-based chemotherapy were eligible. DTX (80 mg/m2) and CPT-11 (100 mg/m2) were given biweekly with filgrastim support (300 µg/day on days 4–7). Results: Fifty patients (48 with metastatic and 2 with locally advanced cancer) were enrolled, with a total of 318 cycles being delivered. Thirty-one patients had visceral localizations. All patients had received epirubicin plus paclitaxel, with or without cisplatin, as front-line treatment for advanced disease. Overall, fatigue and diarrhea were the main chemotherapy-related toxicities in this study, being severe in 10 (20%) and 4 (8%) patients. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 18 (36%) and 6 (12%) patients, respectively. Red blood cell transfusions were required in 4 patients. A total of 32 objective responses were registered (overall response rate, ORR = 64%, 95% confidence interval = 49–77%), including 8 complete responses (16%). An additional 8 patients showed stable disease. After a median follow-up of 18 (range 4–29) months, 30 patients were still alive, and 19 were progression free; median progression-free and overall survivals were 10 and 23 months, respectively. Conclusions: Biweekly DTX/CPT-11 with G-CSF support is a well-tolerated and highly effective approach in anthracycline-/paclitaxel-pretreated patients. The very promising ORR and survival outcome observed in this subset of patients with a poor prognosis suggest that this regimen might play a major role in the management of this disease.

Objectives: To study the clinical characteristics, treatment modalities, and outcome of patients with superior sulcus tumors who underwent surgery over a 15-year period. Design: Retrospective clinical study. Methods: Clinical records of all patients operated on for superior sulcus tumors by the same surgical team between 1988 and 2002 were reviewed retrospectively. Results: Sixty-seven patients were operated on in this period. All the patients underwent en bloc lung and chest wall resection. Surgical approaches were as follows: posterolateral thoracotomy according to Paulson (n = 33), combined transcervical and transthoracic approach (n = 33), and isolated transcervical approach (n = 1). Types of pulmonary resection included lobectomies (n = 59), pneumonectomies (n = 2), and wedge resections (n = 6). Pathologic stages were IIB, IIIA, and IIIB in 49 cases, 12 cases, and 6 cases, respectively. Resection was complete in 55 patients (82%). Operative mortality was 8.9% (n = 6). Postoperative treatment was administered in 53 patients (radiotherapy, n=42; chemoradiotherapy, n=9; and chemotherapy, n=2). Overall 2-year and 5-year survival rates were 54.2% and 36.2%, respectively. Five-year survival was significantly higher after complete resection than after incomplete resection (44.9% vs 0%, p=0.000065). The presence of associated major illness negatively affected the outcome (5-year survival, 16.9% vs 52%; p=0.043). Age, weight loss, respiratory impairment, tumor size, presence of nodal disease, and histologic type did not influence the long-term outcome. At multivariate analysis, only the completeness of resection and the absence of associated major comorbidities had an independent positive prognostic value. Conclusions: Superior sulcus tumor remains an extremely severe condition, but long-term survivals may be achieved in a large percentage of cases. The presence of associated major illness and the completeness of resection are the two most important factors affecting the long-term outcome.

Evidence on adjuvant chemotherapy for elderly early breast cancer patients is poor, due to the low number of phase 3 trials. ELDA shows that weekly docetaxel does not prolong DFS compared with standard CMF and worsens quality of life. Non-hematological toxicity is worse with weekly docetaxel. Age, comorbidities and functioning geriatric scales may be predictive of non-hematological side effects. Background Evidence on adjuvant chemotherapy in older women with breast cancer is poor. We tested whether weekly docetaxel is more effective than standard chemotherapy. Patients and methods We carried out a multicenter, randomized phase III study. Women aged 65–79, operated for breast cancer, with average to high risk of recurrence, were allocated 1 : 1 to CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m², days 1, 8) or docetaxel (35 mg/m2 days 1, 8, 15) every 4 weeks, for four or six cycles according to hormone receptor status. Primary end point was disease-free survival (DFS). A geriatric assessment was carried out. Quality of life (QoL) was assessed with EORTC C-30 and BR-23 questionnaires. Results From July 2003 to April 2011, 302 patients were randomized and 299 (152 allocated CMF and 147 docetaxel) were eligible. After 70-month median follow-up, 109 DFS events were observed. Unadjusted hazard ratio (HR) of DFS for docetaxel versus CMF was 1.21 [95% confidence interval (CI) 0.83–1.76,P = 0.32]; DFS estimate at 5 years was 0.69 with CMF and 0.65 with docetaxel. HR of death was 1.34 (95% CI 0.80–2.22,P = 0.26). There was no interaction between treatment arms and geriatric scales measuring patients' ability or comorbidities. Hematological toxicity, mucositis and nausea were worse with CMF; allergy, fatigue, hair loss, onychopathy, dysgeusia, diarrhea, abdominal pain, neuropathy, cardiac and skin toxicity were worse with docetaxel. One death was attributed to CMF and two to docetaxel. Increasing age, impairment in instrumental daily living activities, number of comorbidities and docetaxel treatment were independently associated with severe nonhematological toxicity. QoL was worse with docetaxel for nausea-vomiting, appetite loss, diarrhea, body image, future perspective, treatment side-effects and hair loss items. Conclusions Weekly docetaxel is not more effective than standard CMF as adjuvant treatment of older women with breast cancer and worsens QoL and toxicity. ClinicalTrials.gov NCT00331097.

Background The management of breast cancer (BC) skin metastases represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin with temporary permeabilization induced by locally administered electric pulses. Preliminary experience with ECT in BC patients is encouraging. Methods A total of 125 patients with BC skin metastases who underwent ECT between 2010 and 2013 were enrolled onto a multicenter retrospective cohort study. The treatment was administered following the European Standard Operative Procedures of Electrochemotherapy. Tumor response was clinically assessed adapting the Response Evaluation Criteria in Solid Tumors, and toxicity was evaluated according to Common Terminology Criteria for Adverse Events 4.0. Cox regression analysis was used to identify predictive factors. Results Response was evaluable in 113 patients for 214 tumors (median 1 per patient, range 1–3). The overall response rate after 2 months was 90.2 %, while the complete response (CR) rate was 58.4 %. In multivariate analysis, small tumor size (P