Same action in different spatial locations induces selective modulation of body metric representation.

Recent studies have hypothesized that the stereotypical representation of the body may reflect some functional aspects of routine actions that are performed in specific peripersonal domains. For example, the lower and upper limbs tend to 'act' in different peripersonal spaces and perform different functions. The present study aims to directly investigate the relationship between body representation and the spatial context where actions are performed. By means of a modified version of the body image task, we investigated body representation before and after a sorting task training in two groups of participants who were asked to carry out the same task/actions in two different spaces: on a table or on the floor, while sitting on a chair. Findings showed that a significant recalibration of the perceived upper arms' length occurred when participants were asked to perform a motor task on the floor. These results seem to suggest that the modulation of the body representation reflects an increase action capabilities driven by the contribution of motor training, and importantly, the location in which the action occurs. Furthermore, the modulation was not limited to the body part actively involved in the action (the arms), it extended to other upper body parts (the torso) to maintain, we propose, a functionally coherent representation of the upper body.

PIK3CA Mutation in the ShortHER Randomized Adjuvant Trial for Patients with Early HER2+ Breast Cancer: Association with Prognosis and Integration with PAM50 Subtype.

PURPOSE: We explored the prognostic effect of PIK3CA mutation in HER2+ patients enrolled in the ShortHER trial. PATIENTS AND METHODS: The ShortHER trial randomized 1,253 patients with HER2+ breast cancer to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. PIK3CA hotspot mutations in exon 9 and 20 were analyzed by pyrosequencing. Expression of 60 genes, including PAM50 genes was measured using the nCounter platform. RESULTS: A mutation of the PIK3CA gene was detected in 21.7% of the 803 genotyped tumors. At a median follow-up of 7.7 years, 5-year disease-free survival (DFS) rates were 90.6% for PIK3CA mutated and 86.2% for PIK3CA wild-type tumors [HR, 0.84; 95% confidence interval (CI), 0.56-1.27; P = 0.417]. PIK3CA mutation showed a favorable prognostic impact in the PAM50 HER2-enriched subtype (n = 232): 5-year DFS 91.8% versus 76.1% (log-rank P = 0.049; HR, 0.46; 95% CI, 0.21-1.02). HER2-enriched/PIK3CA mutated versus wild-type tumors showed numerically higher tumor-infiltrating lymphocytes (TIL) and significant upregulation of immune-related genes (including CD8A, CD274, PDCD1, and MYBL2, a proliferation gene involved in immune processes). High TILs as well as the upregulation of PDCD1 and MYBL2 were associated with a significant DFS improvement within the HER2-enriched subtype (HR, 0.82; 95% CI, 0.68-0.99; P = 0.039 for 10% TILs increment; HR, 0.81; 95% CI, 0.65-0.99; P = 0.049 for PDCD1 expression; HR, 0.72; 95% CI, 0.53-0.99; P = 0.042 for MYBL2 expression). CONCLUSIONS: PIK3CA mutation showed no prognostic impact in the ShortHER trial. Within the HER2-enriched molecular subtype, patients with PIK3CA mutated tumors showed better DFS versus PIK3CA wild-type, which may be partly explained by upregulation of immune-related genes.

Prognostic significance of changes in CA 15-3 serum levels during chemotherapy in metastatic breast cancer patients.

Tumor response to first-line chemotherapy in advanced breast cancer offers prognostic information and may be used as a surrogate marker for evaluating treatment efficacy. With this study we wanted to determine whether changes in circulating serum CA 15-3 levels during chemotherapy provided additional information for prognostic prediction. Serum CA 15-3 was measured at baseline and after 3 and 6 months during anthracycline-based first-line chemotherapy in 526 patients with advanced breast cancer prospectively enrolled in five phase II-III trials. Changes in marker levels were correlated with disease response, time to progression and overall survival. In all, 336 patients attained a disease response. A significant relationship was found between disease response and CA 15-3 variations, although many individual discrepancies were also observed. At the 6-month time point, the median time to progression was 15.3 months in patients with normal marker levels throughout the study, 11.7 months in those with a CA15-3 reduction >25%, 9.6 months in those with elevated baseline CA 15-3 levels which did not change during therapy and 8.6 months in those with increased marker levels (p < 0.001). The median survival was 42.3, 29.7, 28.5, and 24.8 months, respectively (p < 0.002). The prognostic role of changes in CA 15-3 levels was maintained in the patient subset attaining disease response or stabilization to treatment (p < 0.001) and after adjusting for clinical response and major prognostic parameters in the multivariate analysis (p < 0.001). In conclusion, monitoring serum CA 15-3 levels during first-line chemotherapy in advanced breast cancer patients provides prognostic information independently from tumor response.

Combination regimen of epirubicin, vinorelbine and 5-fluorouracil continuous infusion as first-line chemotherapy in anthracycline-naive metastatic breast cancer patients.

We investigated the activity and toxicity of a combination of vinorelbine 25 mg/m2 on days 1 and 15; epirubicin 25 mg/m2 on days 1, 8, 15; and 5-fluorouracil continuous infusion at 200 mg/m2 every day, administered as first-line chemotherapy in anthracycline-naive metastatic breast cancer patients. Fifty-three patients entered the study. Cycles were repeated every 28 days. Objective response was 60% by World Health Organisation (WHO) criteria and 63% by Response Evaluation Criteria in Solid Tumours (RECIST). The median time to progression was 12.7 months (17.6 months in responders) and the median survival duration was 32.9 months. The dose-limiting toxicity was leucopenia (grade 3/4 in 36% of patients). Grade 3/4 non-haematological toxicities included mucositis in 11% of patients, skin and cardiac toxicity in 4% and 2%, respectively. The combination of vinorelbine, epirubicin and 5-fluorouracil continuous infusion was found to be an active and manageable first-line regimen for metastatic breast cancer patients.

Metaplastic breast carcinoma: pathology and clinical outcome.

Metaplastic breast carcinomas are rare neoplasms showing both carcinomatous and sarcomatous elements. In this report we describe eleven cases of metaplastic breast carcinoma focusing on pathological features and the clinical behaviour of six patients with breast carcinoma with chondroid metaplasia (MCC). We collected eleven cases from 1996 to 2001: immunohistochemical tests were performed in order to obtain data on estrogen and progesterone receptors and the production of p53 gene and HER/2 neu. Neoangiogenesis was studied counting vessels immunohistochemically-stained with CD31 antibody. Six cases showed chondroid metaplasia, three cases were spindle cell carcinoma and two were metaplastic squamous carcinoma. The majority of patients (64%) had pT2 tumors without axillary node metastases: only two cases with spindle or squamous metaplasia showed nodal involvement. Fifty percent of MCC were pT1b-c tumors: no axillary metastases were observed. Vascular invasion was observed in all squamous and spindle cell types and in 66% of MCC: estrogen and progesterone receptors were absent in 90% of the tumors. Immunohistochemical staining for HER2/neu was detected in 72% of spindle cell and squamous carcinomas and in 33% of MCC. Three cases staining highly for p53 were chondroid carcinomas: the staining was uniform both in carcinomatous and in sarcomatous tissue. The majority of metaplastic carcinomas had high angionesis. One patient with a chondroid metaplastic carcinoma was found to be a carrier of a BRCA1 mutation similar to the one responsible for sickle cell disease, possibly altering the spatial structure of the gene product. Only six patients had follow-up periods longer than 36 months: five women were alive and disease-free: one patient with pT2N1 squamous metaplastic carcinoma died of disease 14 months after diagnosis. The six women with MCC were alive and disease-free. Surgical and adjuvant treatment should follow the guidelines for the other most common breast cancers even if the need for chemotherapy is unknown due to the absence of large series randomized or observational data.