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In case of suspected hereditary predisposition to digestive cancers, next-generation sequencing can analyze simultaneously several genes associated with an increased risk of developing these tumors. Thus, "Gastro Intestinal" (GI) gene panels are commonly used in French molecular genetic laboratories. Lack of international recommendations led to disparities in the composition of these panels and in the management of patients. To harmonize practices, the Genetics and Cancer Group (GGC)-Unicancer set up a working group who carried out a review of the literature for 31 genes of interest in this context and established a list of genes for which the estimated risks associated with pathogenic variant seemed sufficiently reliable and high for clinical use. Pancreatic cancer susceptibility genes have been excluded. This expertise defined a panel of 14 genes of confirmed clinical interest and relevant for genetic counseling: APC, BMPR1A, CDH1, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, POLD1, POLE, PTEN, SMAD4 and STK11. The reasons for the exclusion of the others 23 genes have been discussed. The paucity of estimates of the associated tumor risks led to the exclusion of genes, in particular CTNNA1, MSH3 and NTHL1, despite their implication in the molecular pathways involved in the pathophysiology of GI cancers. A regular update of the literature is planned to up-grade this panel of genes in case of new data on candidate genes. Genetic and epidemiological studies and international collaborations are needed to better estimate the risks associated with the pathogenic variants of these genes either selected or not in the current panel., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Introduction: Next generation sequencing allows the simultaneous analysis of large panel of genes for families or individuals with a strong suspicion of hereditary breast and/or ovarian cancer (HBOC). Because of lack of guidelines, several panels of genes potentially involved in HBOC were designed, with large disparities not only in their composition but also in medical care offered to mutation carriers. Then, homogenization in practices is needed., Methods: The French Genetic and Cancer Group (GGC) - Unicancer conducted an exhaustive bibliographic work on 18 genes of interest. Only publications with unbiased risk estimates were retained., Results: The expertise of each 18 genes was based on clinical utility criteria, i.e. a relative risk of cancer of 4 and more, available medical tools for screening and prevention of mutation carriers, and pre-symptomatic genetic tests for relatives. Finally, 13 genes were selected to be included in a HBOC diagnosis gene panel: BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN, RAD51C, RAD51D, MLH1, MSH2, MSH6, PMS2, EPCAM. The reasons for excluding NBN, RAD51B, CHEK2, STK11, ATM, BARD1, BRIP1 from the HBOC diagnosis panel are presented. Screening, prevention and genetic counselling guidelines were detailed for each of the 18 genes., Discussion: Due to the rapid increase in knowledge, the GGC has planned a yearly update of the bibliography to take into account new findings. Furthermore, genetic-epidemiological studies are being initiated to better estimate the cancer risk associated with genes which are not yet included in the HBOC diagnosis panel., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Severe thrombocytopenia is a rare but life-threatening side effect of cytotoxic chemotherapy for which risk factors are not well known. Our objective was to delineate a risk model for chemotherapy-induced thrombocytopenia requiring platelet transfusions in cancer patients. Univariate and multivariate analysis of risk factors for chemotherapy-induced thrombocytopenia requiring platelet transfusions were performed on the cohort of the 1,051 patients (CLB 1996) treated with chemotherapy in the Department of Medicine of the Centre Léon Bérard (CLB) in 1996. In univariate analysis, performance status (PS) greater than 1, platelet count less than 150, 000/microL at day 1 (d1) before the initiation of chemotherapy, d1 lymphocyte count < or = 700/microL, d1 polymorphonuclear leukocyte count less than 1,500/microL, and the type of chemotherapy (high risk v others) were significantly associated (P < .01) with an increased risk of severe thrombocytopenia requiring platelet transfusions. Using logistic regression, d1 platelet count less than 150,000/microL (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.9 to 9.6), d1 lymphocyte counts < or = 700/microL (OR, 3.37; 95% CI, 1.77 to 6.4), the type of chemotherapy (OR, 3.38; 95% CI, 1.77 to 6.4), and PS greater than 1 (OR, 2.23; 95% CI, 1.22 to 4.1) were identified as independent risk factors for platelet transfusions. The observed incidences of platelet transfusions were 45%, 13%, 7%, and 1.5% for patients with > or = 3, 2, 1, or 0 risk factors, respectively. This model was then tested in 3 groups of patients treated with chemotherapy used as validation samples: (1) the series of 340 patients treated in the CLB in the first 6 months of 1997, (2) the prospective multicentric cohort of 321 patients of the ELYPSE 1 study, and (3) the series of 149 patients with non-Hodgkin's lymphoma treated in the CLB within prospective phase III trials (1987 to 1995). In these 3 groups, the observed incidences of platelet transfusions in the above-defined risk groups did not differ significantly (P > .1) from those calculated in the model. This risk index could be useful to identify patients at high risk for chemotherapy-induced thrombocytopenia requiring platelet transfusions.

Background: Two previous phase II trials of docetaxels as first line chemotherapy of advanced breast cancer have been conducted by the Clinical Screening Group of the EORTC. In these 2 studies, docetaxel 100 mg/m2 and 75 mg/m2 were administered without routine premedication and produced overall response rates of 68% and 52% respectively. Fluid retention was the most problematic adverse event in these 2 studies in which premedication was not routinely administered. This study investigated the efficacy and safety profile of docetaxel with a 1-day prophylactic premedication., Patients and Methods: Docetaxel 100 mg/m2 was administered intravenously over 1 hour, every 3 weeks, to 37 women (aged 29-65 years) with advanced breast cancer. A 1-day regimen of intravenous antihistamine and oral corticosteroids was given with each dose. Full doses of docetaxel were administered in 179 of 200 cycles (89.5%), giving a median relative dose intensity of 0.98., Results: Tumour regression was achieved in 25 patients (7.66%) after a median of 7 weeks, and 2 patients (5.4%) had a complete response. Response rates were 67.9% in patients with visceral metastases, 76.9% in liver metastases and 83.3% in patients with > 2 organs involved. The median time to progression was 31 weeks (range 1-36+). After a median follow-up time of 6.9 months (range 4.6-9.4), 31 patients (83.7%) were still alive. The most common adverse events (AE) were neutropenia (97%), alopecia (97%, grade 1-2), fluid retention (89%, mainly mild to moderate) and neurosensory disorders (81%, mainly mild to moderate). Only 5 patients experienced febrile neutropenia requiring hospitalisation and/or antibiotic therapy. Sixteen patients discontinued treatment because of fluid retention; nevertheless, 13 of these achieved an objective antitumour response and none had any significant deterioration in performance status. AEs were generally reversible and easily managed, and there were no deaths attributable to docetaxel-related AEs., Conclusions: Docetaxel produces very effective tumour response with acceptable tolerability when used as first-line chemotherapy in patients with advanced breast cancer. The 1-day premedication regimen used in this study was less effective in reducing the incidence and severity or delaying the onset of fluid retention than the currently recommended 5-day corticosteroid premedication. The optimum premedication regimen remains to be defined.

The taxanes, paclitaxel and docetaxel, are the two presents clinically available representatives of a cytotoxic class with a new mechanism of action: they enhance microtubule assembly and inhibit their depolymerization. Their activity has been demonstrated in ovarian, breast and lung cancers. Paclitaxel and docetaxel are also promising agents in the treatment of head and neck, gastric and pancreatic cancer. Neutropenia is the dose limiting toxicity. Currently, use of premedication allows to circumvent hypersensitivity reactions encountered earlier with paclitaxel. For docetaxel, measures to prevent fluid retention are essential.

The authors present a new case of a well-differentiated papillary mesothelioma of the peritoneum. This is an uncommon tumor which have a slow evolution like a low malignant potential tumor. But, because of its tendency to recurrence, the designation of Well-Differentiated Tumor is better. The diagnosis with others peritoneal tumors is sometimes difficult, especially with the Peritoneal Serous Tumors. Tumor recurrence must be treated by curative surgery. Adjuvant therapy is discussed for the diffuse form.

Multiple genome alterations can be seen within a tumor and continue to accumulate throughout development of the growth. Chromosome deletions occurring in tumors are generating much interest. To date, the best known model is retinoblastoma whose study gave rise to the concepts of anti-oncogene or tumor suppressor gene. Studies of genetic anomalies in colorectal tumors have led to an elegant model of colonic carcinogenesis in which multiple steps, each with its corresponding genetic anomaly, successively accumulate, with deletion of the p53 gene occurring as a late event. Successive anomalies of the p53 gene (mutations, deletions) occur during passage from a low-grade astrocytoma to a higher-grade astrocytoma. Studies of familial forms of breast cancer and of breast and ovarian cancer have also provided insight into the biology of these tumors, with the identification of a predisposing chromosomal area whose location is 17 q-12-21. These approaches open up possibilities for screening techniques and use of preventive treatments in highly selected patients. However they raise many ethical problems. There is a need for developing a charter for these family studies in the near future.

Breast cancer remains a key concern for oncologists. The possibility of tamoxifen treatment to prevent breast cancer in high-risk women was one of the central topics discussed for the 1992 ASCO edition. The rationale for the studies being developed in the US and Europe rests on experimental data and results of adjuvant hormone therapy trials. Decreased risks of cancer in the opposite breast, of cardiovascular disease, and of osteoporosis are effects that make tamoxifen extremely attractive for breast cancer prevention trials in postmenopausal women. In premenopausal women, however, preventive tamoxifen should be viewed with special caution because increased incidence of second cancers have been reported, although with dosages higher than those suggested for preventive therapy, and also because of difficulties with defining familial forms. The value of anthracyclines for adjuvant therapy has been demonstrated by several studies. Furthermore, a dose-response relationship has been reported with anthracyclines used as adjuvant therapy or in metastatic disease. New dose-limiting toxic effects, including thrombocytopenia and mucitis, develop when dosages are increased, with concomitant rG-CSF therapy. In patients with metastases, taxol seems to be a promising drug. Ongoing phase I trials seek to determine the optimal dosage and administration modalities for the taxol-doxorubicin combination.