Feasibility, criterion and construct convergent validity of the 2-minute walk test and the 10-meter walk test in an oncological context.

Objective: To examine the feasibility, the criterion, and the construct convergent validity of the 2-Minute Walk Test (2MWT) and the 10-Meter Walk Test (10MeWT) against the 6-Minute Walk Test (6MWT) to assess walking capacity in people with cancer. The criterion concurrent validity of a self-test version of the 10MeWT (10MeWTself-test) was also evaluated against the 10MeWT. Methods: Fifty-six people with cancer performed the 2MWT, the 10MeWT at comfortable and fast speeds, the 6MWT, and the 10MeWTself-test. The feasibility of the tests was assessed using safety, adverse events, space requirements, time taken to administer and interpret the tool, equipment or training required, cost, and portability as criteria. Validity was assessed using Pearson correlation coefficients and Bland Altman plots. Results: The 2MWT, 6MWT, 10MeWT, and 10MeWTself-test were feasible for people with cancer. The 2MWT and the 10MeWT results were moderately to strongly correlated with the 6MWT results (0.61 < r < 0.84, p < 0.001). The 10MeWTself-test results were strongly correlated with the 10MeWT results at comfortable and fast speeds (r = 0.99, p < 0.001). Conclusions: The 2MWT, 10MeWT, and 10MeWTself-test are simple, rapid, and feasible tests for use in people with cancer. The strong correlation between the 2MWT and 6MWT results indicates that the 2MWT can be used as an alternative walking capacity assessment tool. The 10MeWT results moderately correlated with those of the other two tests, suggesting that it partially measures the same construct of walking capacity in walking-independent outpatients with cancer. The 10MeWTself-test showed promising results but needs further investigations in ecological settings.

Hematologic toxicities of chemotherapy in breast and ovarian cancer patients carrying BRCA1/BRCA2 germline pathogenic variants. A single center experience and review of the literature.

BRCA1 and BRCA2 play a central role in DNA repair and their germline pathogenic variants (gBRCA) confer a high risk for developing breast and ovarian cancer. Standard chemotherapy regimens for these cancers include DNA-damaging agents. We hypothesized that gBRCA carriers might be at higher risk of developing chemotherapy-related hematologic toxicity and therapy-related myeloid neoplasms (t-MN). We conducted a retrospective study of women newly diagnosed with invasive breast or ovarian cancer who were screened for gBRCA1/gBRCA2 at Geneva University Hospitals. All patients were treated with (neo-)adjuvant chemotherapy. We evaluated acute hematologic toxicities by analyzing the occurrence of febrile neutropenia and severe neutropenia (grade 4) at day 7-14 of the first cycle of chemotherapy and G-CSF use during the entire chemotherapy regimen. Characteristics of t-MN were collected. We reviewed medical records from 447 patients: 58 gBRCA1 and 40 gBRCA2 carriers and 349 non-carriers. gBRCA1 carriers were at higher risk of developing severe neutropenia (32% vs. 14.5%, p = 0.007; OR = 3.3, 95% CI [1.6-7], p = 0.001) and of requiring G-CSF for secondary prophylaxis (58.3% vs. 38.2%, p = 0.011; OR = 2.5, 95% CI [1.4-4.8], p = 0.004). gBRCA2 carriers did not show increased acute hematologic toxicities. t-MN were observed in 2 patients (1 gBRCA1 and one non-carrier). Our results suggested an increased acute hematologic toxicity upon exposure to chemotherapy for breast and ovarian cancer among gBRCA1 but not gBRCA2 carriers. A deeper characterization of t-MN is warranted with the recent development of PARP inhibitors in frontline therapy in gBRCA breast and ovarian cancer.

Immunotherapy in Urological, Gynecological and Gastrointestinal Cancers - Current Landscape.

Immunotherapy is becoming increasingly important in the management of urological, gynecological, and gastrointestinal cancers. Immune checkpoint inhibitor-based combinations have become a standard of care for patients with metastatic renal and liver cancers, as well as for many patients with bladder, cervical, gastric, and esophageal cancers, based on various biomarkers. Some tumor types are less responsive to immunotherapy, such as prostate and colon cancer. In these tumors, however, a subgroup of patients with a microsatellite-instability-high/DNA-mismatch repair deficient molecular phenotype significantly benefits from immunotherapy. Molecular characterization is therefore essential to identify patients who may benefit from these treatments. One of the major challenges is the search for new predictive biomarkers and novel combinations or strategies to further improve patient outcome.

A multicenter phase II trial of anti-EGFR-immunoliposomes loaded with doxorubicin in patients with advanced triple negative breast cancer.

Advanced triple negative breast cancer (TNBC) is an aggressive, but initially chemo-sensitive disease. The prognosis is poor and more than three quarters of patients experience progression 12 months after the initiation of conventional first-line chemotherapy. Approximately two thirds of TNBC express epidermal growth factor receptor 1 (EGFR). We have developed an anti-EGFR targeted nanocontainer drug by inserting anti-EGFR antibody fragments into the membrane of pegylated liposomes (anti-EGFR-ILs-dox). The payload consists of doxorubicin, a standard drug for TNBC. In a first-in-human phase I trial in 26 patients with various advanced solid malignancies, anti-EGFR-ILs-dox has shown little toxicity and encouraging efficacy. In this single-arm phase II trial, we assessed the efficacy of anti-EGFR-ILs-dox as first-line therapy in patients with advanced, EGFR + TNBC. The primary endpoint was progression-free survival at 12 months (PFS12m). Secondary endpoints included overall response rate (ORR), duration of response (DOR), time to progression (TTP), overall survival (OS) and adverse events (AEs). 48 patients received anti-EGFR-ILs-dox 50 mg/m2 iv, on day one of a 28 days-cycle until progression. The Kaplan-Meier estimate for PFS12m was 13% (one-sided 90% CI 7%, 95% CI [5%, 25%]), median PFS was 3.5 months (95% CI 1.9, 5.4). The trial has not reached its primary endpoint. There were no new toxicity signals. Based on these results, anti-EGFR-ILs-dox should not be further developed for TNBC. It remains an open question whether anti-EGFR-ILs-dox would offer more opportunities in other EGFR-expressing malignancies, where targeting this receptor has already shown anticancer effects.Trial registration: This trial was registered at clinicaltrials.gov: NCT02833766. Registered 14/07/2016.

[Is ketogenic diet effective against cancer ?] / Le régime cétogène : efficace contre le cancer ?

The ketogenic diet, which consists of reduced carbohydrate intake and increased fat intake, is a recognized treatment option for children with intractable epilepsy. This diet is now receiving renewed interest from physicians and researchers because of its potential therapeutic effect in other diseases, such as neurodegenerative diseases, metabolic syndrome or cancer. Since cancer is one of the major public health challenges, complementary approaches to improve the efficacy of standard anti-cancer therapies are the subject of much research. This article reviews the place of the ketogenic diet as a complementary therapy in cancer, the scientific evidence and possible practical aspects of such an approach.

Le régime cétogène vise à réduire l'apport nutritionnel d'hydrates de carbone en augmentant les lipides. Ce régime est une option thérapeutique reconnue, en particulier chez les enfants souffrant d'épilepsie réfractaire. Il fait aujourd'hui l'objet d'un regain d'intérêt de la part des médecins et des chercheurs, en raison de son potentiel effet thérapeutique dans d'autres pathologies comme certaines maladies neurodégénératives, le syndrome métabolique ou même le cancer. Le cancer étant l'un des grands défis de santé publique, les approches complémentaires pour améliorer l'efficacité des thérapies anticancéreuses standards font l'objet de nombreuses recherches. Cet article fait le point sur la place du régime cétogène comme thérapie complémentaire dans le cancer, les évidences scientifiques et les éventuels aspects pratiques d'une telle approche.

Differential impact of tamoxifen and aromatase inhibitors on thrombin generation: the prospective HEMOBREAST cohort.

Tamoxifen and aromatase inhibitors (AIs) are potent antitumoral agents against breast cancer. Tamoxifen increases the risk of venous thromboembolism (VTE), but the influence of AIs on the risk of VTE remains unclear. To inform clinical decisions, we evaluated associations of tamoxifen or AIs with changes of surrogate hemostatic biomarkers. This prospective cohort included 107 women with localized breast cancer starting tamoxifen (n = 42) or an AI (n = 65). Thrombin generation (CAT) its sensitivity to thrombomodulin (TM) or activated protein C (APC), and specific coagulation parameters, were measured before and 10-16 weeks after initiation of treatmen Compared with baseline, endogenous thrombin potential and thrombin peak increased in tamoxifen users (+86 nM × min; 95% confidence interval [CI], 30-142; and +33 nM; 95% CI, 21-45) but not in AI users (n = 65; +44 nM × min; 95% CI, -4 to 93; and +7 nM; 95% CI, -3 to 17). Normalized TM sensitivity ratios increased with tamoxifen (+0.26; 95% CI, 0.19-0.33y) but not with AI (+0.02; 95% CI, -0.03 to 0.07). Plasma levels of fibrinogen, antithrombin, protein C, and Tissue Factor Pathway Inhibitor decreased, and free protein S increased with tamoxifen but not with AIs. The observed shift toward increased coagulability associated with tamoxifen is in line with its known increased risk of VTE. In contrast, AIs do not appear to impact hemostasis, suggesting a lack of associated VTE risk. The trial was registered at www.clinicaltrials.gov as #NCT03381963.

Influence of chemotherapy on postural control and quality of life in women with gynaecological cancer: a protocol of a prospective observational study.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy is a frequent side effect of some chemotherapies that can cause postural control disorders and has a serious impact on quality of life (QoL). An enhanced understanding of postural control dysfunction could help build a systematic and accurate assessment as well as specific exercises to limit the impact on QoL. This study aims to assess the influence of chemotherapy on postural control and the QoL for women with gynaecological cancer. METHODS AND ANALYSIS: This prospective observational study will include 37 participants with cancer treated using neurotoxic chemotherapy. Their postural control in various conditions (rigid and foam surfaces, eyes open and closed, with and without tendon vibration, and dual tasks), limits of stability, QoL and modified Total Neuropathy Score will be assessed. A linear mixed model will compare postural control pre-chemotherapy and post-chemotherapy. ETHICS AND DISSEMINATION: This study was approved by an ethical review board in Geneva (CCER-2020-01639). The study findings will be disseminated through conference presentations and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04692168.

Ovarian cancer with high-level focal ERBB2 amplification responds to trastuzumab and pertuzumab.

Epithelial ovarian cancer (EOC) is usually diagnosed at an advanced stage and significantly contributes to cancer mortality in women. Despite multimodal treatment associating chemotherapy and surgery, most patients ultimately progress and require palliative systemic therapy. In EOC, the efficacy of anti-HER2 agents is minimal even after selecting patients for HER2 expression. ERBB2 gene amplification is observed in 3-10% of patients, depending on the specific method of detection and cutoffs. We report the case of a young woman with a FIGO stage IV high-grade serous ovarian cancer with an amplification of ERBB2. She was treated with the association of trastuzumab - pertuzumab after two lines of standard treatment and presented an excellent long-lasting partial response after 36 months of treatment. The association of trastuzumab and pertuzumab, without chemotherapy, has not been previously tested in this context and could be more efficacious than monotherapy with either agent. In addition, the significant benefit observed in this case could be attributed to the presence of a high-level focal amplification that is relatively rare and probably more specific than an increase in HER2 expression. In conclusion, prospective trials of the trastuzumab and pertuzumab combination should be considered in an appropriately selected EOC patient population.

Gestational trophoblastic disease in Switzerland: retrospective study of the impact of a regional reference centre.

AIMS OF THE STUDY: The European Society of Medical Oncology (ESMO) recommends that countries should have reference centres to provide adequate diagnosis and treatment of gestational trophoblastic disease. A trophoblastic disease centre in the French-speaking part of Switzerland was inaugurated in 2009. The objectives of this study were to report the activity of the centre during the last 10 years and analyse gestational trophoblastic disease outcomes. METHODS: This was a retrospective study with data collected from all cases of gestational trophoblastic disease referred to the centre from 2009 to 2018. All histological specimens as well as data for treatment and follow-up of gestational trophoblastic disease and neoplasia were reviewed. Clinical features, including age, prognostic score and International Federation of Gynecology and Obstetrics (FIGO) stages (in the case of gestational trophoblastic neoplasia), human chorionic gonadotropin (hCG) follow-up, treatment and outcome were reported. RESULTS: The centre registered 354 patients, and these patients presented 156 cases of partial hydatidiform moles, 163 cases of complete hydatidiform moles and 14 cases of gestational trophoblastic neoplasia. During follow-up, 35 gestational trophoblastic neoplasms were diagnosed after hCG persistence. After pathology review, the overall agreement rates between our centre and a participating provider hospital was 82%. Methotrexate was the first line of single-agent chemotherapy for most patients, with resistance rates of 23%. Multi-agent chemotherapy was used as first-line treatment for five patients. None of the patients followed up by the centre died from gestational trophoblastic disease. CONCLUSIONS: This study reflects the activity of the Swiss trophoblastic disease centre from the French-speaking part of Switzerland created in 2009, and its role as local and national reference centre, in terms of global health, for women with gestational trophoblastic disease.

Publisher Correction: Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes.

BRCA1/BRCA2 genes play a central role in DNA repair and their mutations increase sensitivity to DNA-damaging agents. There are conflicting data regarding the prognostic value of BRCA germline mutations in breast cancer (BC) patients. We collected clinical, pathological and genetic data of a cohort 925 BC patients preselected for genetic screening and treated with neoadjuvant or adjuvant chemotherapy, of whom 266 were BRCA carriers. Overall, 171 women carried a BRCA1 mutation, 95 carried a BRCA2 mutation, and 659 were non-carriers. In the entire cohort, there was a prolonged disease-free survival (DFS) for BRCA carriers (hazard ratio (HR) = 0.63; 95% confidence interval (CI), 0.44-0.90 for BRCA1; HR = 0.72; 95%CI, 0.47-1.1 for BRCA2; p = 0.020) and a trend toward prolonged disease-specific survival (DSS; HR = 0.65; 95%CI, 0.40-1.1 for BRCA1; HR = 0.78; 95%CI, 0.44-1.38 for BRCA2; p = 0.19) though not statistically significant. In the TNBC group, BRCA carriers had prolonged DFS (adjusted HR = 0.50; 95%CI, 0.28-0.89 for BRCA1; adjusted HR = 0.37; 95%CI, 0.11-1.25, for BRCA2; p = 0.034) and DSS (adjusted HR = 0.42; 95%CI, 0.21-0.82 for BRCA1; adjusted HR = 0.45; 95%CI, 0.11-1.9 for BRCA2; p = 0.023). In the non-TNBC group, the BRCA1 or BRCA2 mutations did not have any impact on survival. These results suggest that BRCA1/BRCA2 germline mutations are associated with prolonged survival only if women were diagnosed with TNBC.

Durable response to palbociclib and letrozole in ovarian cancer with CDKN2A loss.

Alterations of the Retinoblastoma (Rb) pathway are frequent in ovarian cancer, typically resulting from CDKN2A down-regulation, CCNE1 amplification, CCND1/2 amplification, and RB1 loss. However, bi-allelic CDKN2A mutation or homozygous deletion is a very rare event, concerning less than 5% of patients.Initial trials with palbociclib in serous ovarian cancer have shown very modest benefit in unselected patient populations, thus underlining the need for a biomarker predicting response. We report the case of a heavily pre-treated patient with a serous ovarian tumor harboring a homozygous deletion of the CDKN2A gene that derived significant, prolonged clinical benefit from palbociclib, a CDK4/6 oral inhibitor, with letrozole. Treatment with palbociclib and letrozole started on February 2018, with an ongoing response after 12 months.In conclusion, homozygous CDKN2A deletion is rare and could be used to predict response to CDK4/6 inhibitors in association with other genomic features. We encourage further trials in this direction.

A population-based cohort of young women diagnosed with breast cancer in Geneva, Switzerland.

PURPOSE: Breast cancer is the most frequently diagnosed cancer among women worldwide. Despite the fact that breast cancer is more frequent after fifty years of age, breast cancer among young women has recently drawn particular attention due to an increase in incidence in several western countries. With the exception of individuals with a high genetic risk, breast cancer occurring in younger women remains poorly understood. This project aims at investigating the patient, tumour and treatment characteristics as well as the long-term health outcomes of these women by evaluating numerous variables that were collected from their pathology and medical files, including the social environment, family history, fertility and pregnancy. PARTICIPANTS: We constituted a population-based cohort from the Geneva Cancer Registry of 1586 patients with breast cancer who were aged less than 46 years at the time of diagnosis. FINDINGS TO DATE: Breast cancer was diagnosed before the age of 35 years in 225 women (14.2%), between 35 and 39 years of age in 368 women (23.2%) and between 40 and 45 years of age in 993 women (62.6%). Most of the patients were diagnosed with luminal A or luminal B molecular subtypes (32.8 and 37.5%, respectively), stage I or II tumours (75.2%), and estrogen (74.8%) and progesterone (67.5%) positive receptors. During the study period, 16.7% of these women developed loco-regional recurrences and 25.4% developed distant metastases; the majority (66.3%) did not have a recurrence. Regarding mortality, 474 (29.9%) women died during the study period, 347 (73.2%) from breast cancer. FUTURE PLANS: The results of this study will help filling the knowledge gap about treatment of young breast cancer patients and having a child after breast cancer, and will provide clinicians and public health professionals' with additional information to improve quality of care and decrease the impact of breast cancer in young women.

[Doctor, is it reasonable for me to pursue a physical activity in my condition?] / Docteur, une activité physique dans mon état est-ce bien raisonnable ?

The prevalence of cancer is increasing, with an estimated number of new cases of 21.6 million worldwide by 2030. Progress in cancer therapies has turned it into a chronic disease. Physical exercise is essential both for the general population and for oncology patients. Practicing exercise reduces the risk of developing certain cancer types and, in oncologic patients, it can reduce symptoms secondary to the disease and to treatment as well as decrease the risk of relapsing. Encouraging adapted physical exercise to every oncologic patient is therefore essential (or crucial). It is recommended to practice regular physical activity equivalent to 150 minutes of moderate intensity or 75 minutes of high intensity activity per week.

La prévalence du cancer est en augmentation avec 21,6 millions de nouveaux cas dans le monde d'ici 2030. L'évolution des traitements permet de faire du cancer une maladie chronique. L'activité physique est une question essentielle à la fois au sein de la population générale, mais également pour les patients oncologiques. La pratique d'une activité physique permet de diminuer le risque de survenue de certains cancers mais également, pour les patients oncologiques, de réduire les symptômes liés à la maladie et aux traitements et le risque de récidive. Favoriser une activité physique adaptée pour chaque patient oncologique est donc fondamental. Les recommandations préconisent une activité physique régulière correspondant à 150 minutes d'activité d'intensité modérée ou 75 minutes d'activité d'intensité élevée par semaine.

[Hypnotherapy in psycho-oncology : clinical benefits and future prospects]. / Hypnothérapie en psycho-oncologie : bénéfices cliniques et perspectives d'avenir.

After a cancer diagnosis, emotional distress is common. We currently have many conventional treatments such as radiotherapy, surgery, chemotherapy, targeted therapies and immunotherapy to fight cancer. However, these treatments are associated with significant adverse effects, which may themselves be the cause of psychic suffering. Hypnosis has been shown to be effective in relieving some of these symptoms, but its practice is still limited in oncology. This is as much related to ignorance about the discipline as to a lack of large randomized prospective studies. This article provides an overview of hypnotherapy and its benefits in the field of psycho-oncology and discusses the prospects for the future.

Pour lutter contre le cancer, nous disposons à l'heure actuelle de nombreux traitements tels que la chirurgie, la radiothérapie, la chimiothérapie, mais également les thérapies ciblées et l'immunothérapie. La détresse émotionnelle pouvant accompagner le diagnostic peut parfois s'aggraver en raison des effets indésirables des traitements entrepris. Il est démontré que l'hypnose médicale est efficace pour soulager certains des symptômes présentés, pourtant sa pratique en oncologie reste limitée, probablement en raison de la méconnaissance de cet outil et d'un manque de grandes études prospectives randomisées. Cet article se propose de faire un état des lieux de l'hypnothérapie et de ses bénéfices dans le domaine de la psycho-oncologie et identifie les perspectives d'avenir.

Molecular apocrine tumours in EORTC 10994/BIG 1-00 phase III study: pathological response after neoadjuvant chemotherapy and clinical outcomes.

BACKGROUND: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of MA cancers. METHODS: Centrally assessed biopsies for AR, ER, PR, HER2 and Ki67 by IHC were classified into six subtypes: MA, triple-negative (TN) basal-like, luminal A, luminal B HER2 negative, luminal B HER2 positive and "other". The two main objectives were the pCR rates and survival outcomes in the overall MA subtype (and further divided by HER2 status) and the remaining five subtypes. RESULTS: IHC subtyping was obtained in 846 eligible patients. Ninety-three (11%) tumours were classified as the MA subtype. Both IHC and GEA data were available for 64 patients. In this subset, IHC concordance was 88.3% in identifying MA tumours compared with GEA. Within the MA subtype, pCR was observed in 33.3% of the patients (95% CI: 29.4-43.9) and the 5-year recurrence-free interval was 59.2% (95% CI: 48.2-68.6). Patients with MA and TN basal-like tumours have lower survival outcomes. CONCLUSIONS: Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered.

Towards the first targeted therapy for triple-negative breast cancer: Repositioning of clofazimine as a chemotherapy-compatible selective Wnt pathway inhibitor.

Wnt signaling is overactivated in triple-negative breast cancer (TNBC) and several other cancers, and its suppression emerges as an effective anticancer treatment. However, no drugs targeting the Wnt pathway exist on the market nor in advanced clinical trials. Here we provide a comprehensive body of preclinical evidence that an anti-leprotic drug clofazimine is effective against TNBC. Clofazimine specifically inhibits canonical Wnt signaling in a panel of TNBC cells in vitro. In several mouse xenograft models of TNBC, clofazimine efficiently suppresses tumor growth, correlating with in vivo inhibition of the Wnt pathway in the tumors. Clofazimine is well compatible with doxorubicin, exerting additive effects on tumor growth suppression, producing no adverse effects. Its excellent and well-characterized pharmacokinetics profile, lack of serious adverse effects at moderate (yet therapeutically effective) doses, its combinability with cytotoxic therapeutics, and the novel mechanistic mode of action make clofazimine a prime candidate for the repositioning clinical trials. Our work may bring forward the anti-Wnt targeted therapy, desperately needed for thousands of patients currently lacking targeted treatments.

BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients.

PURPOSE: BRCA1 and BRCA2 proteins are central to DNA repair process through homologous recombination. We hypothesize that BRCA1/BRCA2 mutation carriers may exhibit increased hematological toxicity when receiving genotoxic chemotherapy. METHODS: We included women with primary breast cancers screened for BRCA1/BRCA2 germline mutations and treated with (neo)adjuvant chemotherapy in Geneva (Swiss cohort). The primary endpoint was the incidence of febrile neutropenia following the first chemotherapy cycle (C1). Secondary endpoints were the incidence of grade 3-4 neutropenia, grade 4 neutropenia and hospitalization during C1, G-CSF use and chemotherapy dose reduction during the entire chemotherapy regimen. Long-term toxicities (hematological, cardiac and neuropathy) were assessed in the Swiss cohort and a second cohort of patients from Lyon (French cohort). RESULTS: Overall, 221 patients were assessed for acute hematological toxicity, including 23 BRCA1 and 22 BRCA2 carriers. Following the C1, febrile neutropenia had an incidence of 35% (p = 0.002), 14% (p = 0.562) and 10% among BRCA1, BRCA2 and non-carriers, respectively. Grade 4 neutropenia was found in 57% of BRCA1 (p < 0.001), 14% of BRCA2 (p = 0.861) and 18% of non-carriers. G-CSF support was necessary in 86% of BRCA1 (p = 0.005), 64% of BRCA2 (p = 0.285) and 51% of non-carriers. For long-term toxicity analysis, 898 patients were included (167 BRCA1-, 91 BRCA2- and 640 non-carriers). There was no difference between the 3 groups. CONCLUSIONS: BRCA1 germline mutations is associated with greater acute hematological toxicity in breast cancer patients. These observations could have implication for primary prophylaxis with G-CSF.

[« Doctor, I am fasting during chemotherapy ¼ : illusion or new clinical facts ?] / « Docteur, je jeûnelors de la chimiothérapie ¼ : illusion ou nouvelle réalité clinique ?

Fasting concomitantly with oncology treatments (chemotherapy mainly) induces a growing interest among patients following overmediatisation of recent discoveries. The goal of this article is to provide updated information about this approach. According to preclinical studies, fasting may be a way to increase the therapeutic index of major oncology treatments. However, clinical data is based on small exploratory studies only and the results of larger scale studies are not yet available. The approach of fasting during chemotherapy can and should neither be recommended nor implemented in standard care. However, further scientific and clinical investigation may contribute to a better understanding of the metabolic aspects of cancer.

Jeûner au cours des traitements oncologiques (de la chimiothérapie en particulier) génère un intérêt croissant auprès des patients suite à la surmédiatisation de récentes découvertes. Le but de cet article est de faire un état des lieux sur les bases scientifiques de cette approche. Selon des études précliniques, le jeûne pourrait augmenter l'index thérapeutique des principaux traitements oncologiques. Mais les données cliniques manquent cruellement, malgré quelques données émanant de petites études exploratoires. Les études à plus grande échelle sont en cours. Aujourd'hui, l'approche du jeûne pendant la chimiothérapie ne peut et ne doit être ni recommandée ni introduite dans des protocoles de soins. Son étude peut par contre améliorer la compréhension des aspects métaboliques du cancer.

Do patients whose tumor achieved a pathological response relapse at specific sites? A substudy of the EORTC 10994/BIG-1-00 trial.

PURPOSE: To determine the sites of first distant relapse in patients with or without pCR following neoadjuvant chemotherapy in breast cancer patients enrolled in the EORTC 10994/BIG-1-00 trial. METHODS: We included patients enrolled in the EORTC 10994/BIG-1-00 trial who received at least one chemotherapy cycle before surgery and who had been diagnosed with a distant relapse. pCR was defined as no evidence of residual invasive cancer in the primary tumor and axillary lymph nodes with or without residual ductal carcinoma in situ. Site of first distant relapse was categorized as 'soft tissue,' 'visceral,' 'skeletal,' 'central nervous system (CNS),' and 'other.' The association between relapse site and achievement of pCR was assessed using multivariate logistic regression models for molecular subtypes classification and preceding locoregional recurrence. RESULTS: The study included 383 (21%) eligible patients out of the 1856 randomized, of whom 28 (7%) had achieved pCR. Median follow-up was 5.4 years. Achievement of pCR was associated with a trend towards a decreased presentation of skeletal metastases [21% (pCR) vs. 50% (non-pCR), OR 0.32, adjusted p value = 0.071] and an increase in the proportion of patients with CNS metastases as first distant relapse site (21% vs. 9%, OR 2.39, adjusted p value = 0.183). Patients with pCR were more likely to present with only one relapse location category when compared to non-pCR (86% vs. 69%). CONCLUSION: Patients that achieved a pCR appeared less likely to present with skeletal metastases and more frequently presented with CNS metastases as first site of distant relapse, even after adjustment for molecular subtypes.