Is the breast-conserving treatment with radiotherapy appropriate in mutation carriers? Long-term results and review of the literature

International audienceAs tumours in mutation carriers might be more sensitive to radiation, we investigated after long-term follow-up whether mutation status influenced the rate of ipsilateral and contralateral breast cancers after breast-conserving treatment (BCT). and genes were screened for germline mutations in 131 patients with a family history of breast and/or ovarian cancer who had undergone BCT and radiotherapy. Patients were matched to 261 controls with sporadic breast cancer according to age at diagnosis and year of treatment. Controls were followed up for at least as long as the interval between diagnosis and genetic screening in familial cases. Rates of ipsilateral and contralateral cancer between groups were compared by the log-rank test. The mutations occurred in 20.6% of tested patients. Tumours in mutation carriers were more likely to be grade III ( < 10) and oestrogen receptor negative ( = 0.005) than in non-carriers and controls. Overall median follow-up was 161 months. There was no significant difference in ipsilateral tumours between mutation carriers, non-carriers and controls ( = 0.13). On multivariate analysis, age was the most significant predictor for ipsilateral recurrence ( < 10). The rate of contralateral cancer was significantly higher in familial cases: 40.7% (mutation carriers), 20% (non-carriers), and 11% (controls) ( < 10). After 13.4 years of follow-up, the rate of ipsilateral tumours was no higher in mutation carriers than in non-carriers or controls. As tumours in mutation carriers might be more sensitive to radiation, BCT is a possible treatment option

The First Genomic and Proteomic Characterization of a Deep-Sea Sulfate Reducer: Insights into the Piezophilic Lifestyle of Desulfovibrio piezophilus

Desulfovibrio piezophilus strain C1TLV30T is a piezophilic anaerobe that was isolated from wood falls in the Mediterranean deep-sea. D. piezophilus represents a unique model for studying the adaptation of sulfate-reducing bacteria to hydrostatic pressure. Here, we report the 3.6 Mbp genome sequence of this piezophilic bacterium. An analysis of the genome revealed the presence of seven genomic islands as well as gene clusters that are most likely linked to life at a high hydrostatic pressure. Comparative genomics and differential proteomics identified the transport of solutes and amino acids as well as amino acid metabolism as major cellular processes for the adaptation of this bacterium to hydrostatic pressure. In addition, the proteome profiles showed that the abundance of key enzymes that are involved in sulfate reduction was dependent on hydrostatic pressure. A comparative analysis of orthologs from the non-piezophilic marine bacterium D. salexigens and D. piezophilus identified aspartic acid, glutamic acid, lysine, asparagine, serine and tyrosine as the amino acids preferentially replaced by arginine, histidine, alanine and threonine in the piezophilic strain. This work reveals the adaptation strategies developed by a sulfate reducer to a deep-sea lifestyle

Influenza Epidemics in the United States, France, and Australia, 1972–19971

Influenza epidemics occur once a year during the winter in temperate areas. Little is known about the similarities between epidemics at different locations. We have analyzed pneumonia and influenza deaths from 1972 to 1997 in the United States, France, and Australia to examine the correlation over space and time between the three countries. We found a high correlation in both areas between France and the United States (correlation in impact, Spearman’s ρ = 0.76, p < 0.001, and test for synchrony in timing of epidemics, p < 0.001). We did not find a similar correlation between the United States and Australia or between France and Australia, when considering a systematic half-year lead or delay of influenza epidemics in Australia as compared with those in the United States or France. These results support a high correlation at the hemisphere level and suggest that the global interhemispheric circulation of epidemics follows an irregular pathway with recurrent changes in the leading hemisphere

Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review

Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients’ characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05–1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6–13/20 vs. 10–18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use

Lymphome non Hodgkinien après cancer du sein (étude rétrospective de 46 patientes suivies à l'Institut Curie)

Le cancer du sein est le cancer féminin le plus fréquent. En France, il atteint environ une femme sur douze. L'amélioration du dépistage et de la prise en charge thérapeutique a permis d'obtenir de nombreuses survivantes à long terme et ce, quel que soit le stade initial de la maladie. Ces femmes peuvent secondairement développer un second cancer. Aucun facteur de risque génétique et/ou lié aux traitements n'a été démontré. Parmi plus de 30000 patientes suivies à l'institut Curie pour un cancer du sein depuis plus de 30 ans, nous avons recensé 57 femmes ayant développé secondairement un lymphome non Hodgkinien. Quarante six d'entre elles ont été analysées dans cette étude rétrospective. L'âge médian au diagnostic de cancer du sein était de 57 ans. Plus de 90% des patientes ont reçu un traitement par radiothérapie, en association pour 13% (6) d'entre elles à de la chimiothérapie. Avec un suivi médian de près de 12 ans, 76 % (35) des patientes étaient en rémission complète. Seuls 14 évènements relatifs au cancer du sein ont été observés. Le delai médian d'apparition du lymphome était de 7,8 ans. L'âge médian était de 63 ans. Les lymphomes de phénotype B étaient majoritairement représentés avec 50 % de lymphomes folliculaires et 30,4% de lymphomes à grandes cellules. Il n'existait aucune anomalie cytogénétique particulière. Toutes ces patientes ont pu recevoir un traitement adapté. avec un suivi médian de 4,3 ans, 32,6% (15) étaient en rémission complète. Deux patientes ont été perdues de vue et 22 (47,8%) sont décédées du lymphome. Comme dans les lymphomes de novo, le pronostic était lié au grade histologique, avec un avantage de survie pour les lymphomes de bas grade...PARIS7-Villemin (751102101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Combination of Modern Radiotherapy and New Targeted Treatments for Breast Cancer Management

Background: The objective of the present study was to review the essential knowledge about the combinations of the most commonly used or under development targeted treatments and radiation therapy (RT). Methods: Preclinical and clinical studies investigating this combination were extensively reviewed. Results: Several studies showed that the combination of RT and tamoxifen increased the risk of radiation-induced pulmonary toxicity; therefore, both modalities should not be given concomitantly. The combination of HER2 inhibitors (trastuzumab, pertuzumab) and RT seems to be safe. However, trastuzumab emtansine (T-DM1) should not be administered concurrently with brain RT since this combination could increase the risk of brain radionecrosis. The combination of RT and other new target treatments such as selective estrogen receptor degradants, lapatinib, cell cycle inhibitors, immune checkpoint inhibitors, or molecules acting on DNA damage repair seems feasible but was essentially evaluated on retrospective or prospective studies with a small number of patients. Furthermore, there is considerable heterogeneity among these studies regarding the dose and fractionation of radiation, the dosage of drugs, and the sequence of treatments used. Conclusions: The combination of RT with most targeted therapies for BC appears to be well-tolerated, but these results need to be confirmed in prospective randomized studies