Dancing With Health: Quality of Life and Physical Improvements From an EU Collaborative Dance Programme With Women Following Breast Cancer Treatment.

Background: Women's health has received renewed attention in the last few years including health rehabilitation options for women affected by breast cancer. Dancing has often been regarded as one attractive option for supporting women's well-being and health, but research with women recovering from breast cancer is still in its infancy. Dancing with Health is multi-site pilot study that aimed to evaluate a dance programme for women in recovery from breast cancer across five European countries. Methods: A standardized 32 h dance protocol introduced a range of Latin American dances presented within a sports and exercise framework with influences from dance movement therapy. Fifty-four women (M age 53.51; SD 7.99) participated in the study who had a breast cancer diagnosis <3 years, chemotherapy >6 weeks, no indication of metastasis, or scheduled surgery/chemotherapy/radiation treatment for the duration of the intervention. Primary outcome data was collected for anthropometric and fitness measures next to cancer-related quality of life. T-tests and Wilcoxon signed ranked tests were used to establish differences pre and post intervention. Cohen's d was also calculated to determine the effect size of the intervention. Results: Statistically significant changes were found for: (i) weight, right and left forearm circumference and hip; (ii) 6 min walking, right and left handgrip, sit-to-stand and sit-and-reach; (iii) the EORTC-QLQ C30 summary score as well as the subscales of emotional and social functioning and symptoms. In all cases the direction of change was positive, while Cohen's d calculated showed that the effect of the intervention for these parameters ranged from intermediate to large. Conclusion: Changes on the above anthropometric, fitness and quality of life measures suggest that the intervention was of value to the participating women recovering from breast cancer. Results also advocate collaborative efforts across countries to further research.

The recovery of reaching movement in breast cancer survivors: two different rehabilitative protocols in comparison.

BACKGROUND: Breast cancer (BC) is the most common cancer in women in the developed world. The about the sequelae of surgery, especially in case of mastectomy or modified radical mastectomy is grown. Nowadays it is important choose appropriate exercise programs to allow recovery in "quantity" but also in "quality" of the movement of the operated upper limb. AIM: The aim of this study was to verify whether specific exercises for the scapula may induce changes in fluidity of the reaching movement. DESIGN: Randomized control-trial double-blind study. SETTING: Exercise training laboratory and gait analysis laboratory. POPULATION: Sixty-three breast cancer survivors were enrolled. METHODS: Participants randomized to single rehabilitative treatment (ST), or to group rehabilitative treatment (GT). VAS, DASH and a biomechanical evaluation of upper limb were performed for each group before treatment (T0=baseline), at the end rehabilitative treatment (T1) and after three months of follow-up (T2). RESULTS: Respect within group analysis, in the ST and in the GT, for VAS an improvement along evaluation times were observed, respectively at T0 to T1 and at T0 to T2 (P<0.001) without a statistically significant difference between groups. At the same, for the DASH, the results showed the same trend without a statistically significant difference between groups. For biomechanical parameters, at T2 velocity was statistically significantly greater in the ST than in the GT (P=0.029) in contrast with the duration, that was statistically significantly greater in the GT than in the ST (P=0.010). CONCLUSIONS: Both protocols are effective in reducing pain and for functional recovery of the upper limb. The adoption of a non-intensive rehabilitation program should be implemented at least in the first year after the operation, with the adoption of specific myofascial exercises on the scapulo-thoracic joint with better results in the "qualitative" recovery of the achievement. CLINICAL REHABILITATION IMPACT: Our study emphasizes the importance of rehabilitation in BC survivors after mastectomy, even during the course of radiotherapy and chemotherapy and the adoption of specific myofascial exercises on the scapulo-thoracic joint and specific exercises of muscular stretching on the pectoral muscle. Therefore, the proposed rehabilitation protocol must be "clipped" and "integrated" according to the specific objectives for each individual patient.

IL-10, IL-13, Eotaxin and IL-10/IL-6 ratio distinguish breast implant-associated anaplastic large-cell lymphoma from all types of benign late seromas.

Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is an uncommon peripheral T cell lymphoma usually presenting as a delayed peri-implant effusion. Chronic inflammation elicited by the implant has been implicated in its pathogenesis. Infection or implant rupture may also be responsible for late seromas. Cytomorphological examination coupled with CD30 immunostaining and eventual T-cell clonality assessment are essential for BI-ALCL diagnosis. However, some benign effusions may also contain an oligo/monoclonal expansion of CD30 + cells that can make the diagnosis challenging. Since cytokines are key mediators of inflammation, we applied a multiplexed immuno-based assay to BI-ALCL seromas and to different types of reactive seromas to look for a potential diagnostic BI-ALCL-associated cytokine profile. We found that BI-ALCL is characterized by a Th2-type cytokine milieu associated with significant high levels of IL-10, IL-13 and Eotaxin which discriminate BI-ALCL from all types of reactive seroma. Moreover, we found a cutoff of IL10/IL-6 ratio of 0.104 is associated with specificity of 100% and sensitivity of 83% in recognizing BI-ALCL effusions. This study identifies promising biomarkers for initial screening of late seromas that can facilitate early diagnosis of BI-ALCL.

The reaching movement in breast cancer survivors: Attention to the principles of rehabilitation.

INTRODUCTION: Breast-cancer is leading cause of morbidity and mortality in women. The prognosis and survival rate of women with breast-cancer have significantly improved worldwide; more attention needs to be paid to rehabilitative interventions after surgery. This paper describes use of reaching movement to assess upper limb motorcontrol and functional ability after breast-cancer surgery (BC). MATERIAL AND METHODS: We conducted a cross-sectional observational study consisting of biomechanical evaluation of upper limb limitations in women BC, versus a controlgroup (CG). Thirty breast-cancer survivors and thirty healthy women participated in this study. Both groups were subjected to clinical evaluation of the shoulder joint ROM on the operated side, as an assessment of the muscular-strength of the shoulder with the MRC-scale. The Functional-Assessment was evaluated by the DASH and Constant-Murley-Score. The EORTC QLQ-C30 and VAS were used to measure the quality of life assessment and pain respectively. A Biomechanical evaluation was performed, using Reaching-Task and Surface-EMG. RESULTS: Normal Jerk for BC was higher than CG. Target approaching velocity and movement duration BC was lower than CG. Synergy Anterior Deltoid/Triceps Brachii muscles in CG was higher than BC.

Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers.

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches.

Changes in Spine Alignment and Postural Balance After Breast Cancer Surgery: A Rehabilitative Point of View.

Breast cancer is the most common malignant tumor in female patients in developed countries. Recent articles indicate that one-sided mastectomy or minor breast surgery to treat breast cancer can have deleterious effects on posture and the musculoskeletal system. The purpose of this study was to investigate the alterations post-breast cancer surgery of the spine alignment associated to the balance not reported by the noninvasive instrumentation. We enrolled 30 women who had undergone treatment for breast cancer (BG) and were on a waiting-list for rehabilitation treatment and a control group of 30 healthy volunteer women (CG), matched by age and body mass index. The stabilometry was performed using a force platform (Kistler Instruments, Winterthur, Switzerland) test during quiet standing with closed-eyes (EC) and open-eyes (EO), recording the position of the center of pressure (CoP) for 51.2 sec. The stabilogram or the time plot of the two coordinates, X and Y, of the CoP was obtained, which represent anteroposterior and midlateral balance. Spinal posture was measured using the Formetric-4D rasterstereographic system (DIERS, International GmbH, Schlangenbad, Germany), and thoracic kyphotic angle, lumbar lordotic angle, and surface trunk rotation were evaluated. Sixty participants were analyzed (CG:30; BG:30). For the spine rasterstereography a statistically significant difference was shown with regard to anterior-posterior flexion of the trunk major in BG; pelvic inclination and twist of half-pelvis decreased in BG; normalized lumbosacral inversion point decreased in BG; surface rotation major in BG; and lateral deviation major in BG. Compared with the values for the stabilometry test with EO and EC, a statistically significant difference was observed, respectively, for ellipse length (mm; p = 0.04) and ellipse area (mm2; p = 0.04) with EO and in ellipse area (mm2) with EC (p = 0.05), increased in BG for both conditions. No difference was shown for CoP velocity and oscillations between the groups. Breast cancer survivors after prostheses or tissue expanders for mastectomy showed a spine's misalignment present both on the sagittal plane, both on the coronal and frontal plane, increased in BG regard to anterior-posterior flexion of the trunk, surface rotation, and lateral deviation. It is associated with greater energy expenditure for the postural balance control increased in BG with a major ellipse area in EO and EC conditions and major ellipse length in EC condition.

The sexist behaviour of immune checkpoint inhibitors in cancer therapy?

BACKGROUND: Immune checkpoint inhibitors, targeting the molecules CTLA-4, PD-1 and PD-L1, showed efficacy against several type of cancers and are currently used in clinical practice. An important biological variable that influences innate and adaptive immunity is the sex, acting through genetic, hormonal and environmental factors. The overall differences between sexes could be crucial to evaluate the response to ICIs. MATERIALS AND METHODS: We performed a meta-analysis of Phase II-III Clinical Trials published up to June 2017 in which anti-CTLA-4, anti-PD-1 and anti-PD-L1 were studied. We extracted the OS and PFS HR differentiated by sex from subgroups analysis of each trial. We analyzed the three classes of drugs separately. RESULTS: We selected 36 Phase II-III Clinical Trials, 9 of which reported results for OS and 6 for PFS. We analyzed 2 Clinical Trials for OS with anti-CTLA-4, including 1178 patients, observing a benefit for males vs females (HR 0.65, 95% CI 0.55-0.77 vs HR 0.79, 95% CI 0.65-0.96, p 0.078).Not statistically significant results were observed with anti-PD-1 neither for OS (males vs females: HR 0.72, 95% CI 0.64-0.83 vs HR 0.81, 95% CI 0.70-0.94, p 0.285) neither for PFS (males vs females: HR 0.66, 95% CI 0.52-0.82 vs HR 0.85, 95% CI 0.66-1.09, p 0.158). We cannot perform a meta-analysis for anti-PD-L1 due to the lack of data. CONCLUSIONS: Different mechanisms could be involved in sex differences with regard to immunotherapy. These differences could be relevant to identify immunological targets in order to draw studies exploring novel combinations of immunotherapy agents.

Reply to the Letter of Terracini B. et al. "Comment on Piscitelli et al. Hospitalizations in Pediatric and Adult Patients for All Cancer Type in Italy: The EPIKIT Study under the E.U. COHEIRS Project on Environment and Health". Int. J. Environ. Res. Public Health 2017, 14, 495.

A letter to the IJERPH Editor was submitted by Terracini B. et al. as a comment to our latest paper "Hospitalizations in Pediatric and Adult Patients for all Cancer Type in Italy:[...].

Cytological diagnostic features of late breast implant seromas: From reactive to anaplastic large cell lymphoma.

Late breast implant seroma may be the presentation of a breast implant-associated anaplastic large cell lymphoma (BI-ALCL), which claims for a prompt recognition. However, BI-ALCL diagnosis on fine-needle aspiration (FNA) might be challenging for pathologists lacking experience with peri-implant breast effusions. Sixty-seven late breast implant seromas collected by FNA from 50 patients were evaluated by Papanicolaou smear stain and immunocytochemistry on cell blocks. A diagnostic algorithm based on the cellular composition, cell morphology and percentage of CD30+ cells was developed. Histological evaluation of the corresponding peri-prosthetic capsules was also performed. Most of the effusions (91% of the samples) were classified as reactive and 9% as BI-ALCL. In the BI-ALCL cases, medium-to-large atypical cells expressing CD30 represented more than 70% of the cellularity, whereas in in the reactive effusions CD30+ elements were extremely rare (<5%) and consisted of non-atypical elements. The reactive effusions were categorized into three patterns: i) acute infiltrate with prominent neutrophilic component (33% of the samples); ii) mixed infiltrate characterized by a variable number of neutrophils, lymphocytes and macrophages (30% of the samples); iii) chronic infiltrate composed predominantly of T lymphocytes or macrophages with only sporadic granulocytes (37% of the samples). The inflammatory cytological patterns were consistent with the histology of the corresponding capsules. Our results indicate that cytological analysis of late breast implant effusions, supported by the knowledge of the heterogeneous cytomorphological spectrum of late seromas, is a valuable approach for the early recognition of BI-ALCL.

Hospitalizations in Pediatric and Adult Patients for All Cancer Type in Italy: The EPIKIT Study under the E.U. COHEIRS Project on Environment and Health.

Background: Cancer Registries (CRs) remain the gold standard for providing official epidemiological estimations. However, due to CRs' partial population coverage, hospitalization records might represent a valuable tool to provide additional information on cancer occurrence and expenditures at national/regional level for research purposes. The Epidemiology of Cancer in Italy (EPIKIT) study group has been built up, within the framework of the Civic Observers for Health and Environment: Initiative of Responsibility and Sustainability (COHEIRS) project under the auspices of the Europe for Citizens Program, to assess population health indicators. Objective: To assess the burden of all cancers in Italian children and adults. Methods: We analyzed National Hospitalization Records from 2001 to 2011. Based on social security numbers (anonymously treated), we have excluded from our analyses all re-hospitalizations of the same patients (n = 1,878,109) over the entire 11-year period in order to minimize the overlap between prevalent and incident cancer cases. To be more conservative, only data concerning the last five years (2007-2011) have been taken into account for final analyses. The absolute number of hospitalizations and standardized hospitalization rates (SHR) were computed for each Italian province by sex and age-groups (0-19 and 20-49). Results: The EPIKIT database included a total of 4,113,169 first hospital admissions due to main diagnoses of all tumors. The annual average number of hospital admissions due to cancer in Italy has been computed in 2362 and 43,141 hospitalizations in pediatric patients (0-19 years old) and adults (20-49 years old), respectively. Women accounted for the majority of cancer cases in adults aged 20-49. As expected, the big city of Rome presented the highest average annual number of pediatric cancers (n = 392, SHR = 9.9), followed by Naples (n = 378; SHR = 9.9) and Milan (n = 212; SHR = 7.3). However, when we look at SHR, minor cities (i.e., Imperia, Isernia and others) presented values >10 per 100,000, with only 10 or 20 cases per year. Similar figures are shown also for young adults aged 20-49. Conclusions: In addition to SHR, the absolute number of incident cancer cases represents a crucial piece of information for planning adequate healthcare services and assessing social alarm phenomena. Our findings call for specific risk assessment programs at local level (involving CRs) to search for causal relations with environmental exposures.

Positive impact of elastography in breast cancer diagnosis: an institutional experience.

Elastography (ES) is a technique that, when associated with traditional B mode ultrasound (US), allows the degree of elasticity of tissue to be evaluated according to a color scale system. The aims of the study were to compare the diagnostic characteristics of two widely used techniques adopted in breast cancer screening; US and color Doppler (CD), with those of the same two techniques plus ES, and assessment of the same diagnostic characteristics when the three methods were applied to lesions < or >1 cm. Methods used included subjecting 212 women to investigations aimed at the early diagnosis of breast cancer outside the screening model, whereby 395 lesions were detected by US, ES, and CD, with a definitive diagnosis proved by histological exam. The diagnostic performance of US, ES, CD, and their combinations was calculated. The results showed that comparing the diagnostic characteristics of the three methods with reference to the definitive histological results for malignant breast lesions, the best diagnostic accuracy was obtained when US, ES, and CD were combined (0.837). For lesions <1 cm, diagnostic accuracy was 0.782, and for those >1 cm, it was 0.886. In the lesions <1 cm, which were more difficult to study, a positive ES score (>4) appeared to be sufficient to deepen the diagnosis, even though 35 % of the ES or US positive lesions were not malignant. By contrast, in lesions >1 cm, the probability of having a malignant lesion when all three tests were positive was very high (97 %). It was concluded that early diagnosis is a key factor in breast cancer, so an economically sustainable, non-invasive pathway is the target of diagnostic breast imaging.

Diagnostic and therapeutic path of breast cancer: effectiveness, appropriateness, and costs--results from the DOCMa study.

OBJECTIVE: An increase in breast cancer incidence has been documented in Italy and in other countries, and some women decide by themselves to undergo diagnostic examinations outside the official screening campaigns. The aim of this paper was to analyze - in terms of effectiveness, appropriate access, and related costs - the path spontaneously followed by a sample of Italian women for the early diagnosis of breast cancer. SUBJECTS AND METHODS: A total of 143 women who consecutively referred themselves to the breast cancer outpatient facilities at the Sant'Andrea University Hospital in Rome from May to June 2007 were enrolled in the study, gave their consent, and were screened according to their individual risk factors for breast cancer. The entire diagnostic and therapeutic path followed in the previous 2 years by each of them, either at Sant'Andrea or in other medical facilities, was reviewed and evaluated in terms of its operative efficiency and fair economic value. RESULTS: The subjects' mean age was 47.5 years (standard deviation 13.6 years); 55% of the women were <50 years old (28% <40 years), and were thus not included in the official screening campaigns; 97 women (70%) were requesting a routine control; and 49% of them had already undergone four to seven examinations before the enrollment, although no major risk factor was present in 73.5%. After enrollment in the study, nine of the patients had surgical interventions performed on them at Sant'Andrea's, identifying five invasive carcinomas and two ductal in situ carcinomas and two benign lesions. Operative efficiency and fair economic value were found to be optimal only in diagnostic/therapeutic paths followed at Sant'Andrea. CONCLUSION: The diagnostic path at Sant'Andrea's specialized center for breast cancer diagnosis and therapy is characterized by higher operative efficiency and more sustainable costs than at general hospitals, outpatient facilities run by local health authorities, or private medical centers. This result seems to confirm the present tendency to refer high-risk patients for breast cancer directly to breast units like the one at Sant'Andrea.

High-resolution, handheld camera use for occult breast lesion localization plus sentinel node biopsy (SNOLL): a single-institution experience with 186 patients.

BACKGROUND: Sentinel node and occult lesion localization (SNOLL) calls for a combination of two specific procedures: intraoperative detection of sentinel lymph node (SLN) via gamma probe and radioguided occult lesion localization (ROLL). This applies to nonpalpable invasive breast cancer or high-grade in situ carcinoma. As opposed to standard techniques, today's handheld gamma cameras enable intraoperative scintigraphic images. METHODS: A cohort (N = 186) of consecutive patients with breast cancer was subjected to radioguided conservative surgery (quadrantectomy and SLN biopsy), using a standard gamma probe and a high-resolution handheld camera. Intraoperative SLN frozen section was also performed. RESULTS: Neoplastic lesions were removed in 99.4% of all patients, and SLN biopsy was achieved in 99%. Of the 137 patients with invasive cancer, SLN metastasis was confirmed in 21. In 12% of patients, a second operation was required for close or tumor-positive surgical margins. DISCUSSION: This combination of procedures represents an improvement in the surgical management of occult breast carcinomas and is the method of choice for accurate tumor localization and SLN biopsy. Handheld cameras have the potential to become highly useful intraoperative aids.

FCGRs Polymorphisms and Response to Trastuzumab in Patients With HER2-Positive Breast Cancer: Far From Predictive Value?

BACKGROUND: The aim of the study was to validate the association between the Arg166His polymorphisms of the Fc immunoglobulin receptor 2A (FCGR2A) and the Val212Phe of FCGR3A and pathological clinical response (pCR) to trastuzumab in HER2-positive breast cancer patients. METHODS: Polymorphisms were characterized by pyrosequencing in 26 patients with ductal histotype breast cancer in a neoadjuvant setting and genotype association with pCR was analyzed. RESULTS: No association was found between the FCGR3A Val212Phe polymorphisms and pCR. In contrast, the FCGR2A GG genotype (Arg allele) was found to be positively associated with pCR (P = 0.012). CONCLUSIONS: Our results do not support previously reported data on the effect of polymorphisms in immunoglobulin Fc receptors upon response to trastuzumab therapy.

Accuracy rates of US-guided vacuum-assisted breast biopsy.

A prospective study designed to measure the accuracy of mammography (MRx), ultrasound (US), fine-needle aspiration cytology (FNAC) and one of the most recently introduced techniques, vacuum biopsy (VB), in the diagnosis of breast cancer is reported. A sample of 146 breast lesions on 135 patients were examined. The design of the study made it possible to compare MRx, US, FNAC and VB directly, because it excluded several confounding variables. Statistical indicators--sensitivity, specificity, predictive values (PPV and NPV), false-negative and false-positive rates (FN and FP), suspicious plus indeterminate rate and likelihood ratios (LR)--were calculated. The NPV of MRx and US were remarkably high (92.4% and 97.9%, respectively), confirming previous reports. The complete sensitivity of FNAC was 80%, while specificity was 99.1% and LR of positive tests 88.8. The combined score of FNAC, US and MRx resulted in a good increase in complete sensitivity (97.1%), when compared with the results of the single diagnostic tests evaluated separately. The absolute sensitivity of VB was 97.1% and specificity was 100%. In conclusion, considered together, MRx, US and FNAC appear to be reliable diagnostic procedures and, when they are all negative, the possibility of a cancer is extremely low, although it cannot be completely ruled out. The VB test had the highest absolute sensitivity among all the methods compared. Therefore, this technique could be considered conclusive in diagnostically doubtful cases, avoiding open surgical biopsy.