BACKGROUNDThe 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. METHODSIn this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher. RESULTSA total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemother apy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease. CONCLUSIONSAmong women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemo-

Frontline aggressive surgical approach to primary RSTS is safe when carried out at high-volume centers. It could be systematically considered in primary RSTS.

Background NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. Patients and methods Patients’ characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series ( N = 35 784) and in the subgroup of incident patient population ( N = 29 497). Results Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li–Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [ P < 0.001 for all, with a hazard ratio of 0.681 (95% CI 0.618–0.749) for OS]. Conclusion This nationwide registry of sarcoma patients shows that surgical treatment in a reference center reduces the risk of relapse and death.

These authors equally contributed to this work.yy These authors jointly supervised this work. Keywords: B cells, gastric cancer, histology, human tumors, prognosis, T-betAbbreviations: APC, antigen presenting cell; DC, dendritic cell; NK, natural killer; OS, overall survival; RFS, relapse-free survival; Th1, T helper type 1; TLS, tertiary lymphoid structures; Treg, regulatory T cell.Tumor-infiltrating T and B lymphocytes could have the potential to affect cancer prognosis. The objective of this study was to investigate the prognostic significance of tumor infiltration by CD8 and CD4 T cells, and B lymphocytes in patients with localized gastric cancer. In a retrospective cohort of 82 patients with localized gastric cancer and treated by surgery we quantitatively assessed by immunohistochemistry on surgical specimen, immune infiltrates of IL-17 C , CD8 C , Foxp3 C , Tbet C T cells and CD20 C B cells both in the tumor core and at the invasive margin via immunohistochemical analyses of surgical specimens. We observed that CD8 C and IL17 C T-cell densities were not significantly associated with gastric cancer prognosis. In contrast, high infiltration of Tbet C T cells, high numbers of CD20 C B-cell follicles, and low infiltration of Foxp3 C T cells, were associated with better relapse-free survival. Interestingly, treatment with neoadjuvant chemotherapy or histological tumor type (diffuse versus intestinal) did not influence type and density of immune infiltrates or their prognostic value. Immunohistochemical analysis of the gastric cancer stromal microenvironment revealed organized T and B cell aggregates, with strong structural analogies to normal secondary lymphoid organs and which could be considered as tertiary lymphoid structures. Using transcriptomic data from an independent cohort of 365 localized gastric cancer, we confirmed that a coordinated Th1, and B cell stromal gene signature is associated with better outcome. Altogether, these data suggest that tumor infiltration by B and Th1 T cells could affect gastric cancer prognosis and may be used to better define the outcome of patients with localized gastric cancer.

The influence of clinical and treatment factors on the risk of recurrence was analyzed from a retrospective series of 74 children and adolescents with thyroid cancer (55 girls, 19 boys; age 2-20 years). Two groups, comparable in terms of age, sex, and previous radiotherapy, were compared according to the presence (group 1) or absence (group 2) of cervical lymph nodes identified by palpation or ultrasonography. Total thyroidectomy (TT) with lymph node dissection (LND) was performed in the 19 group 1 patients, whereas in group 2 patients (n = 55) lobectomy was performed in 29, TT in 26, and LND in 7. Pathology studies showed papillary thyroid carcinoma in 95% of cases. In group 1, tumors were more frequently multifocal (89% vs. 16% in group 2), invasive with extension beyond the thyroid capsule (68% vs. 5% in group 2), and of the diffuse sclerosing variety (63% vs. 4% in group 2) (p < 0.001). With a median follow-up of 61 months, lymph node recurrence was seen in 53% of group 1 patients and in no patients in group 2. Three group 2 patients (10%) were reoperated for a local recurrence after lobectomy. Risk factors for reintervention were young age (< 15 years) (p < 0.01) and cervical lymph nodes (p < 0.001). Survivals without reintervention at 5 and 10 years were, respectively, 58% and 38% for group 1 and 94% and 90% for group 2 (p < 0.001). At the time of analysis, 68% of group 1 patients and 98% of group 2 patients were in remission. In conclusion, the presence of palpable cervical lymph nodes at diagnosis is associated with more invasive forms of malignancy and is a predictive factor of recurrence regardless of the extent of the initial surgery.