RÉSUMÉ
BACKGROUND: Circadian rhythms regulate cellular physiology and could influence the efficacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271). METHODS: 1278 patients with high-risk hormonal receptor positive (HR+)/HER2 negative (HER2-) primary BC were randomly assigned to adjuvant ET with placebo or everolimus. Patients prospectively reported in a diary the daily timing of ET intake among four 6-h slots (06:00-11:59 (morning), 12:00-17:59 (afternoon), 18:00-23:59 (evening), or 24:00-05:59 (nighttime). The association between ET timing and disease-free survival (DFS) was a prespecified secondary endpoint of the trial and the results of this observational study are reported here. FINDINGS: ET timing was recorded by 855 patients (67.2%). Patients declaring morning (n = 465, 54.4%) or afternoon (n = 45, 5.4%) ET intake were older than those declaring evening (n = 339, 39.6%) or nighttime (n = 5, 0.6%) intake. With a median follow-up of 46.7 months, 118 patients had a local (n = 30) or metastasis relapse (n = 84), and 41 patients died. ET intake timing was not associated with DFS in the whole population (HR = 0.77, 95% CI [0.53-1.12]). The association between ET intake timing and DFS according to the stratification factors revealed interactions with ET agent (tamoxifen versus Aromatase inhibitors (AI) with an increased DFS in the group of evening/nighttime versus morning/afternoon tamoxifen intake (HR = 0.43, 95% CI [0.22-0.85]), while no association was found for AI intake (HR = 1.07, 95% CI [0.68-1.69]). The interaction between ET intake timing and ET agent remained in multivariable analysis (HR = 0.38 [0.16-0.91]). INTERPRETATION: Tamoxifen intake in the evening/nighttime could be recommended in patients with high-risk HR+/HER2- BC while awaiting for results from further ET timing studies. FUNDING: UNIRAD was Supported by a grant from the French Ministry of Health PHRC 2012 and received funding from La Ligue contre le Cancer, Cancer Research-UK, Myriad Genetics, and Novartis.
Sujet(s)
Tumeurs du sein , Adulte , Sujet âgé , Femelle , Humains , Adulte d'âge moyen , Antinéoplasiques hormonaux/usage thérapeutique , Antinéoplasiques hormonaux/administration et posologie , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/mortalité , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Traitement médicamenteux adjuvant/méthodes , Rythme circadien , Survie sans rechute , Stadification tumorale , Tamoxifène/administration et posologie , Tamoxifène/usage thérapeutique , Résultat thérapeutique , Études prospectivesRÉSUMÉ
Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of diagnosis. Preliminary epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this nationwide cohort study, we assessed the association between medication use at breast cancer diagnosis and survival. We included 235,368 French women with newly diagnosed non-metastatic breast cancer. In analyzes of 288 medications, we identified eight medications positively associated with either overall survival or disease-free survival: rabeprazole, alverine, atenolol, simvastatin, rosuvastatin, estriol (vaginal or transmucosal), nomegestrol, and hypromellose; and eight medications negatively associated with overall survival or disease-free survival: ferrous fumarate, prednisolone, carbimazole, pristinamycin, oxazepam, alprazolam, hydroxyzine, and mianserin. Full results are available online from an interactive platform ( https://adrenaline.curie.fr ). This resource provides hypotheses for drugs that may naturally influence breast cancer evolution.
Sujet(s)
Tumeurs du sein , Humains , Femelle , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/épidémiologie , Tumeurs du sein/anatomopathologie , Études de cohortes , Comorbidité , SimvastatineRÉSUMÉ
Importance: Targeted therapies directed against ERBB2 are the cornerstone of medical treatment for ERBB2-positive breast cancers but are contraindicated during pregnancy. Objectives: To describe the association of exposure to anti-ERBB2 agents during pregnancy with pregnancy and fetal or newborn outcomes, and to compare the risk and types of adverse outcomes reported more frequently in this context than after exposure to other anticancer agents. Design, Setting, and Participants: For this case-control study, All reports with a pregnancy-related condition and an antineoplastic agent (Anatomical Therapeutic Chemical classification group L01) registered in the World Health Organization international pharmacovigilance database VigiBase up to June 26, 2022, were extracted. All reports with a pregnancy, an antineoplastic treatment during pregnancy, and a cancer were retained. Reports with anticancer agents prescribed for nononcologic purposes were not included. Exposure: The exposure group was defined as reports that mention anti-ERBB2 agents compared with exposure to other anticancer agents. Main Outcome and Measures: The main outcome was the reporting odds ratio (ROR) for maternofetal complications in the group exposed to anti-ERBB2 agents compared with other anticancer agents, as determined using a disproportionality analysis. Results: A total of 3558 reports (anti-ERBB2 agents, 328; other anticancer agents, 3230) were included in the analysis. In the group exposed to anti-ERBB2 agents, most reports were from the US (159 [48.5%]), the mean (SD) age of participants was 30.8 (10.4) years, and 209 patients (97.7%) were treated for breast cancers. The molecules most frequently involved in cases with anti-ERBB2 agents were trastuzumab (n = 302), pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18). The outcomes overreported in these cases included oligohydramnios (ROR, 17.68 [95% CI, 12.26-25.52]; P < .001), congenital respiratory tract disorders (ROR, 9.98 [95% CI, 2.88-34.67]; P < .001), and neonatal kidney failure (ROR, 9.15 [95% CI, 4.62-18.12]; P < .001). Sensitivity and multivariable analyses found similar results. Toxic effects were also significantly overreported for trastuzumab-emtansine (cardiovascular malformation: ROR, 4.46 [95% CI, 1.02-19.52]) and lapatinib (intrauterine growth restriction: ROR, 7.68 [95% CI, 3.01-19.59]). Conclusions and Relevance: In this case-control study of 328 individuals exposed to anti-ERBB2 agents during pregnancy, exposure was associated with a severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments.
Sujet(s)
Antinéoplasiques , Tumeurs du sein , Nouveau-né , Femelle , Grossesse , Humains , Adulte , Lapatinib , Études cas-témoins , Trastuzumab/effets indésirables , Ado-trastuzumab emtansine , Tumeurs du sein/traitement médicamenteux , Antinéoplasiques/effets indésirables , Récepteur ErbB-2RÉSUMÉ
BACKGROUND/AIM: Olaparib was approved in 2014 by the European Medicines Agency (EMA) as maintenance treatment for patients with breast cancer gene (BRCA)-mutated platinum-sensitive relapsed high-grade epithelial ovarian cancer (EOC) following the results of the Study 19. We present the results of a national real-world study on the effectiveness of olaparib in relapsed BRCA-mutated EOC patients. PATIENTS AND METHODS: Patients with EOC, peritoneal, and/or fallopian-tube cancer treated with olaparib in a French Center between May 2014 and March 2017 were included. The primary end-point of the study was progression-free survival. RESULTS: Of the 128 patients analyzed, 89 were treated according to the EMA label. The median progression-free survival was 17.0 months. The most common treatment-related toxicity was fatigue. Treatment-related myelodysplastic syndrome (n=5) and a second cancer (n=1) were diagnosed. CONCLUSION: In this real-life setting, olaparib confirmed its efficacy and safety profile, as previously shown in clinical trials.
Sujet(s)
Antinéoplasiques , Tumeurs de l'ovaire , Humains , Femelle , Carcinome épithélial de l'ovaire/traitement médicamenteux , Carcinome épithélial de l'ovaire/génétique , Antinéoplasiques/usage thérapeutique , Tumeurs de l'ovaire/traitement médicamenteux , Tumeurs de l'ovaire/génétique , Études de cohortes , Phtalazines/effets indésirables , Récidive tumorale locale/traitement médicamenteux , Récidive tumorale locale/génétiqueRÉSUMÉ
OBJECTIVE: To compare the prevalence of contraception in breast cancer (BC) patients at risk of unintentional pregnancy (i.e. not currently pregnant or trying to get pregnant) and matched controls. STUDY DESIGN: The FEERIC study (Fertility, Pregnancy, Contraception after BC in France) is a prospective, multicenter case-control study, including localized BC patients aged 18-43 years, matched for age and parity to cancer-free volunteer controls in a 1:2 ratio. Data were collected through online questionnaires completed on the Seintinelles research platform. RESULTS: In a population of 1278 women at risk of unintentional pregnancy, the prevalence of contraception at study inclusion did not differ significantly between cases (340/431, 78.9%) and controls (666/847, 78.6%, p = 0.97). Contrarily, the contraceptive methods used were significantly different, with a higher proportion of copper IUD use in BC survivors (59.5% versus 25.0% in controls p < 0.001). For patients at risk of unintentional pregnancy, receiving information about chemotherapy-induced ovary damage at BC diagnosis (OR = 2.47 95%CI [ 1.39-4.37] and anti-HER2 treatment (OR = 2.46, 95% CI [ 1.14-6.16]) were significantly associated with the use of a contraception in multivariate analysis. CONCLUSION: In this large French study, BC survivors had a prevalence of contraception use similar to that for matched controls, though almost one in five women at risk of unintentional pregnancy did not use contraception. Dedicated consultations at cancer care centers could further improve access to information and contraception counseling.
Sujet(s)
Tumeurs du sein , Survivants du cancer , Grossesse , Humains , Femelle , Études cas-témoins , Études prospectives , ContraceptionRÉSUMÉ
INTRODUCTION: Somatic genetic tests carried out by new high-throughput sequencing techniques (NGS) are now integrated into the care of children with cancer and leukemia. They can reveal constitutional abnormalities. We questioned the practices of pediatricians in carrying out genetic tests. METHODS: Survey was carried out among pediatric onco-hematologists and residents who have completed a pediatric hematology-oncology internship. RESULTS: Pediatricians mainly prescribe somatic genetic analyses. They are aware that they can reveal constitutional anomalies and inform the parents. Practices in terms of consent to genetics are heterogeneous. The regulatory aspects are poorly known. The child is still little considered in decisions, including when he reaches majority. Parents are informed of the existence of genetic information consultations mainly in the event of suspicion of a constitutional anomaly. Pediatricians, like residents, consider their knowledge of genetics insufficient. Despite this, they feel more comfortable communicating with families while residents say they are uncomfortable conducting a genetic interview. CONCLUSION: Extensive use of NGS for diagnosis confronts pediatricians with ethical questions about information, consent and the return of results. The support of the child must be taken more into account. Ways are mentioned for a better appropriation of the difficulties, while respecting the regulatory framework. The place of the pediatrician and that of the geneticist would aim to be clarified. Specific training, from the internship, would improve support for families and patients.
Sujet(s)
Famille , Leucémie aigüe myéloïde , Enfant , Humains , Dépistage génétique/méthodes , Parents , PédiatresRÉSUMÉ
Background: Long-term changes in lung cancer (LC) patients are difficult to evaluate. We report results from the French KBP-2020 real-life cohort. Methods: KBP-2020 was a prospective cohort that included all patients diagnosed with LC in 2020, in nonacademic public hospital in France. Patient and tumour characteristics were described and compared with similarly designed cohorts in 2000 and 2010. Findings: In 2020, 82 centers included 8,999 patients diagnosed with LC. The proportion of women increased: 34·6% (3114/8999) compared to, 24·3% (1711/7051) and 16·0% (904/5667) in 2010 and 2000 (p<0·0001). The proportion of non-smokers was higher in 2020 (12·6%, 1129/8983) than in previous cohorts (10·9% (762/7008) in 2010; 7·2% (402/5586) in 2000, p<0·0001). In 2020, at diagnosis, 57·6% (4405/7648) of patients had a metastatic/disseminated stage non-small-cell lung cancer (NSCLC) (58·3% (3522/6046) in 2010; 42·6% (1879/4411) in 2000, p<0·0001). Compared with 2000 and 2010 data, early survival improved slightly. In 2020, 3-month mortality of NSCLC varied from 3·0% [2·2 - 3·8] for localized to 9·6% [8·1 - 11·0] for locally advanced to 29·2% [27·8 - 30·6] for metastatic and was 24·8% [22·3 - 27·3] for SCLC. Interpretation: To our knowledge KBP cohorts have been the largest, prospective, real-world cohort studies involving LC patients conducted in worldwide. The trend found in our study shows an increase in LC in women and still a large proportion of patients diagnosed at metastatic or disseminated stage. Funding: The study was promoted by the French College of General Hospital Pulmonologists with financial support of industrials laboratories.
RÉSUMÉ
Surgical studies have specific issues, such as quality assurance on procedures, standardization of techniques, surgeon effect, timing of randomization, blinding respect or choice of the reference arm. All these difficulties conducted to criticism many trials, and lack of results implementation. Indeed, adherence to methodological guidelines is often poor. Twelve recommendations were recently issued by the JAMA surgery revue for good practice in surgical studies to improve the quality of surgical trials in general and surgical oncology. We detail here the main issues of surgical trials in gynaecological oncology surgery, as well as possibilities of improvement for future studies.
Sujet(s)
Oncologie chirurgicale , Humains , Oncologie médicaleRÉSUMÉ
RESEARCH QUESTION: What are the real-life oncofertility practices in young women diagnosed with breast cancer? DESIGN: The FEERIC (FErtility, prEgnancy, contRaceptIon after breast Cancer in France) study is a web-based cohort study launched with the French collaborative research platform Seintinelles. The current work is based on the enrolment self-administered questionnaire of 517 patients with prior breast cancer diagnosis, free from relapse and aged 18 to 43 years at inclusion (from 12 March 2018 to 27 June 2019). RESULTS: Median age at breast cancer diagnosis was 33.6 years and 424 patients (82.0%) received chemotherapy. Overall, 236 (45.6%) patients were offered specialized oncofertility counselling, 181 patients underwent at least one fertility preservation procedure (FPP); 125 (24.2%) underwent one or more FPP with material preservation (oocytes n = 108, 20.9%; embryos n = 31, 6.0%; ovarian cryopreservation n = 6, 1.2%) and 78 patients received gonadotrophin-releasing hormone agonists (15.1%). With a median follow-up of 26.9 months after the end of treatments, 133 pregnancies had occurred in 85 patients (16.4%), including 20 unplanned pregnancies (15.0%). Most of the pregnancies were natural conceptions (n = 113, 87.6%), while 16 (12.4%) required medical interventions. For the planned pregnancies, median time to the occurrence of an ongoing pregnancy was 3 months. Patients who had an unplanned pregnancy reported lower rates of information on the consequences of the treatments on fertility (P = 0.036) at diagnosis. CONCLUSIONS: Most of the patients were not offered proper specialized oncofertility counselling at the time of breast cancer diagnosis. Naturally conceived pregnancies after breast cancer were much more frequent than pregnancies resulting from the use of cryopreserved gametes. Adequate contraceptive counselling seems as important as information about fertility and might prevent unplanned pregnancies.
Sujet(s)
Tumeurs du sein , Survivants du cancer , Préservation de la fertilité , Tumeurs du sein/traitement médicamenteux , Études de cohortes , Cryoconservation , Femelle , Préservation de la fertilité/méthodes , Humains , Récidive tumorale locale , GrossesseRÉSUMÉ
BACKGROUND: Breast cancer (BC) has particular characteristics in young women, with diagnosis at more advanced stages, a poorer prognosis and highly aggressive tumors. In NeoFit, we will use an activity tracker to identify and describe various digital profiles (heart rate, physical activity, and sleep patterns) in women below the age of 45 years on neoadjuvant chemotherapy for BC. METHODS: NeoFit is a prospective, national, multicenter, single-arm open-label study. It will include 300 women below the age of 45 years treated with neoadjuvant chemotherapy for BC. Participants will be asked to wear a Withing Steel HR activity tracker round the clock for 12 months. The principal assessments will be performed at baseline, at the end of neoadjuvant chemotherapy and at 12 months. We will evaluate clinical parameters, such as toxicity and the efficacy of chemotherapy, together with quality of life, fatigue, and parameters relating to lifestyle and physical activity. The women will complete REDCap form questionnaires via a secure internet link. DISCUSSION: In this study, the use of an activity tracker will enable us to visualize changes in the lifestyle of young women on neoadjuvant chemotherapy for BC, over the course of a one-year period. This exploratory study will provide crucial insight into the digital phenotypes of young BC patients on neoadjuvant chemotherapy and the relationship between these phenotypes and the toxicity and efficacy of treatment. This trial will pave the way for interventional studies involving sleep and physical activity interventions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05011721 . Registration date: 18/08/2021.
Sujet(s)
Tumeurs du sein , Traitement néoadjuvant , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Tumeurs du sein/anatomopathologie , Femelle , Humains , Mâle , Études multicentriques comme sujet , Traitement néoadjuvant/méthodes , Études prospectives , Qualité de vieRÉSUMÉ
OBJECTIVES: Immune checkpoint inhibitors have become the standard of care for metastatic non-small-cell lung cancer (NSCLC) progressing during or after platinum-based chemotherapy. Real-world clinical practice tends to represent more diverse patient characteristics than randomized clinical trials. We sought to evaluate overall survival (OS) outcomes in the total study population and in key subsets of patients who received nivolumab for previously treated advanced NSCLC in real-world settings in France, Germany, or Canada. MATERIALS AND METHODS: Data were pooled from two prospective observational cohort studies, EVIDENS and ENLARGE, and a retrospective registry in Canada. Patients included in this analysis were aged ≥18 years, had stage IIIB/IV NSCLC, and received nivolumab after at least one prior line of systemic therapy. OS was estimated in the pooled population and in various subgroups using the Kaplan-Meier method. Timing of data collection varied across cohorts (2015-2019). RESULTS: Of the 2585 patients included in this analyses, 1235 (47.8 %) were treated in France, 881 (34.1 %) in Germany, and 469 (18.1 %) in Canada. Median OS for the total study population was 11.3 months (95 % CI: 10.5-12.2); this was similar across France, Germany, and Canada. The OS rate was 49 % at 1â¯year and 28 % at 2 years for the total study population. In univariable Cox analyses, the presence of epidermal growth factor receptor mutations in nonsquamous disease, liver, or bone metastases were associated with significantly shorter OS, whereas tumor programmed death ligand 1 expression and Eastern Cooperative Oncology Group performance status 0-1 were associated with significantly prolonged OS. Similar OS was noted across subgroups of age and prior lines of therapy. CONCLUSION: OS rates in patients receiving nivolumab for previously treated advanced NSCLC in real-world clinical practice closely mirrored those in phase 3 studies, suggesting similar effectiveness of nivolumab in clinical trials and clinical practice.
Sujet(s)
Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Adolescent , Adulte , Canada , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , France/épidémiologie , Allemagne/épidémiologie , Humains , Tumeurs du poumon/traitement médicamenteux , Nivolumab/usage thérapeutique , Études rétrospectivesRÉSUMÉ
BACKGROUND: Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone. METHODS: This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment. For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years. The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis. DISCUSSION: The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts. TRIALS REGISTRATION: ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing study.
Sujet(s)
Tumeurs osseuses/chirurgie , Tumeurs du sein/chirurgie , Carcinome pulmonaire non à petites cellules/chirurgie , Tumeurs du poumon/chirurgie , Tumeurs de la prostate/chirurgie , Radiochirurgie/méthodes , Adulte , Tumeurs osseuses/secondaire , Tumeurs osseuses/thérapie , Tumeurs du sein/anatomopathologie , Tumeurs du sein/thérapie , Carcinome pulmonaire non à petites cellules/anatomopathologie , Carcinome pulmonaire non à petites cellules/thérapie , Essais cliniques de phase III comme sujet , Association thérapeutique , Femelle , Études de suivi , Humains , Tumeurs du poumon/anatomopathologie , Tumeurs du poumon/thérapie , Mâle , Études multicentriques comme sujet , Pronostic , Tumeurs de la prostate/anatomopathologie , Tumeurs de la prostate/thérapie , Essais contrôlés randomisés comme sujet , Taux de survieRÉSUMÉ
BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used in the treatment of a first ovarian cancer relapse. METHODS: This systematic review, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, aimed to assess the quality of scientific proof of the survival benefits of HIPEC, using Medline and Google Scholar. Qualitative analysis using the Oxford CEBM Levels of Evidence 2011 grading is reported. RESULTS: Of 469 articles identified, 23 were included; 15 based on series of patients treated with HIPEC without a control group, and 8 case control series of patients treated with or without HIPEC. The series without a control group showed median overall survival (OS) ranged from 23.5 to 63 months, highlighting a broad standard deviation. Considering the case control series, OS was significantly better in the HIPEC group in 5 studies, and similar in 1. The current review showed considerable heterogeneity and biases, with an Oxford Level of Evidence grading of 4 for 22 selected series and 2 for one. CONCLUSIONS: There is no strong evidence to suggest efficacy of HIPEC in improving survival of patients treated for a first relapse of ovarian cancer due to the low quality of the data.
RÉSUMÉ
BACKGROUND: Diseases consequence on individual work as much as consequences of being absent from work are matters of interest for decision makers. METHODS: We analyzed lengths of absenteeism and related indirect costs for patients with a paid activity in the year following the diagnosis of early stage breast cancer, in the prospective OPTISOINS01 cohort. Both human capital and friction costs approach were considered for the valuation of lost working days (LWD). For the analysis, the friction period was estimated from recent French data. The statistical analysis included simple and multiple linear regression to search for the determinants of absenteeism and indirect costs. RESULTS: 93 % of the patients had at least one period of sick leave, with on average 2 period and 186 days of sick leave. 24 % of the patients had a part-time resumption after their sick leave periods, during 114 days on average (i.e. 41 LWD). Estimated indirect costs were 22,722.00 and 7,724.00 per patient, respectively for the human capital and the friction cost approach. In the multiple linear regression model, factors associated with absenteeism were: the invasive nature of the tumor (p = .043), a mastectomy (p = .038), a surgery revision (p = .002), a chemotherapy (p = .027), being a manager (p = .025) or a craftsman (p = .005). CONCLUSION: Breast cancer lead to important lengths of absenteeism in the year following the diagnosis, but almost all patients were able to return to work. Using the friction cost or the human capital approach in the analysis led to an important gap in the results, highlighting the importance of considering both for such studies.
Sujet(s)
Absentéisme , Tumeurs du sein/économie , Reprise du travail , Congé maladie/économie , Tumeurs du sein/thérapie , Traitement médicamenteux adjuvant , Études de cohortes , Coûts indirects de la maladie , Femelle , France , Humains , Mastectomie , Adulte d'âge moyen , Invasion tumorale , Professions , Affectation du personnel et organisation du temps de travail/économie , RéinterventionRÉSUMÉ
Immunosurveillance plays an important role in breast cancer (BC) prognosis and progression, and can be geared by immunogenic chemotherapy. In a cohort of 1023 BC patients treated with neoadjuvant chemotherapy (NAC), 40% of the individuals took comedications mostly linked to aging and comorbidities. We systematically analyzed the off-target effects of 1178 concurrent comedications (classified according to the Anatomical Therapeutic Chemical (ATC) Classification System) on the density of tumor-infiltrating lymphocytes (TILs) and pathological complete responses (pCR). At level 1 of the ATC system, the main anatomical classes of drugs were those targeting the nervous system (class N, 39.1%), cardiovascular disorders (class C, 26.6%), alimentary and metabolism (class A, 16.9%), or hormonal preparations (class H, 6.5%). At level 2, the most frequent therapeutic classes were psycholeptics (N05), analgesics (N02), and psychoanaleptics (N06). Pre-NAC TIL density in triple-negative BC (TNBC) was influenced by medications from class H, N, and A, while TIL density in HER2+ BC was associated with the use of class C. Psycholeptics (N05) and agents acting on the renin-angiotensin system (C09) were independently associated with pCR in the whole population of BC or TNBC, and in HER2-positive BC, respectively. Importantly, level 3 hypnotics (N05C) alone were able to reduce tumor growth in BC bearing mice and increased the anti-cancer activity of cyclophosphamide in a T cell-dependent manner. These findings prompt for further exploration of drugs interactions in cancer, and for prospective drug-repositioning strategies to improve the efficacy of NAC in BC.
Sujet(s)
Traitement néoadjuvant , Tumeurs du sein triple-négatives , Animaux , Humains , Lymphocytes TIL , Souris , Études prospectives , Récepteur ErbB-2 , Tumeurs du sein triple-négatives/traitement médicamenteuxRÉSUMÉ
EVIDENS is an ongoing, prospective, non-interventional study evaluating the effectiveness and safety of nivolumab in lung cancer patients in France (ClinicalTrials.gov NCT03382496). Adults with a pathologically confirmed diagnosis of lung cancer and initiating treatment with nivolumab were recruited from 146 sites in France. This analysis included only patients with non-small cell lung cancer (NSCLC) who received ≥1 nivolumab infusion, and evaluated patient characteristics at the time of nivolumab initiation and its effectiveness and safety after a median follow-up of 18 months. A total of 1,420 patients with NSCLC were included, most of whom had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (82.9%), non-squamous histology (69.2%) and stage IV disease (91.4%). Brain metastases were present in 19.9% of patients. Nivolumab was a second-line or ≥third-line regimen in 73.6% and 26.1% of patients, respectively. Almost all patients had prior chemotherapy (99.7%). Median overall survival was 11.2 months (95% confidence interval [CI]: 10.0-12.4). ECOG PS, smoking status, corticosteroids at baseline, epidermal growth factor receptor mutation status, presence of symptomatic brain metastases and treatment-related adverse events (TRAEs) were independent predictors of survival. Grade 3 and 4 TRAEs were reported in 105 (7.4%) and 12 (0.8%) patients, respectively; no treatment-related deaths were reported. Preliminary results of the EVIDENS study confirm the effectiveness and safety of nivolumab, mostly in pre-treated advanced NSCLC patients, with similar benefits to those observed in the phase III randomized clinical trials, despite a broader study population.
Sujet(s)
Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Adulte , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , France/épidémiologie , Humains , Tumeurs du poumon/traitement médicamenteux , Nivolumab/effets indésirables , Études prospectivesRÉSUMÉ
Predictive biomarkers for tumor response to neoadjuvant chemotherapy are needed in breast cancer. This study investigates the predictive value of 280 genes encoding proteins that regulate microtubule assembly and function. By analyzing 3 independent multicenter randomized cohorts of breast cancer patients, we identified 17 genes that are differentially regulated in tumors achieving pathological complete response (pCR) to neoadjuvant chemotherapy. We focused on the MTUS1 gene, whose major product, ATIP3, is a microtubule-associated protein down-regulated in aggressive breast tumors. We show here that low levels of ATIP3 are associated with an increased pCR rate, pointing to ATIP3 as a predictive biomarker of breast tumor chemosensitivity. Using preclinical models of patient-derived xenografts and 3-dimensional models of breast cancer cell lines, we show that low ATIP3 levels sensitize tumors to the effects of taxanes but not DNA-damaging agents. ATIP3 silencing improves the proapoptotic effects of paclitaxel and induces mitotic abnormalities, including centrosome amplification and multipolar spindle formation, which results in chromosome missegregation leading to aneuploidy. As shown by time-lapse video microscopy, ATIP3 depletion exacerbates cytokinesis failure and mitotic death induced by low doses of paclitaxel. Our results favor a mechanism by which the combination of ATIP3 deficiency and paclitaxel treatment induces excessive aneuploidy, which in turn results in elevated cell death. Together, these studies highlight ATIP3 as an important regulator of mitotic integrity and a useful predictive biomarker for a population of chemoresistant breast cancer patients.
Sujet(s)
Aneuploïdie , Antinéoplasiques d'origine végétale/pharmacologie , Tumeurs du sein/traitement médicamenteux , Résistance aux médicaments antinéoplasiques/génétique , Protéines tumorales/physiologie , Paclitaxel/pharmacologie , Protéines suppresseurs de tumeurs/physiologie , Tumeurs du sein/génétique , Tumeurs du sein/métabolisme , Lignée cellulaire tumorale , Cytocinèse/effets des médicaments et des substances chimiques , ADN tumoral/effets des médicaments et des substances chimiques , Analyse de profil d'expression de gènes , Hétérogreffes , Humains , Microtubules/effets des médicaments et des substances chimiques , Microtubules/physiologie , Études multicentriques comme sujet/statistiques et données numériques , Traitement néoadjuvant , Invasion tumorale/génétique , Transplantation tumorale , Interférence par ARN , Essais contrôlés randomisés comme sujet/statistiques et données numériques , Appareil du fuseau/effets des médicaments et des substances chimiques , Appareil du fuseau/ultrastructure , Taxoïdes/pharmacologie , Imagerie accélérée , Protéines suppresseurs de tumeurs/antagonistes et inhibiteurs , Protéines suppresseurs de tumeurs/génétiqueRÉSUMÉ
INTRODUCTION: The organization of health care for breast cancer (BC) constitutes a public health challenge to ensure quality of care, while also controlling expenditure. Few studies have assessed the global care pathway of early BC patients, including a description of direct medical costs and their determinants. The aims of this multicenter prospective study were to describe care pathways of BC patients in a geographic territory and to calculate the global direct costs of early stage BC during the first year following diagnosis. METHODS: OPTISOINS01 was a multicenter, prospective, observational study including early BC patients from diagnosis to one-year follow-up. Direct medical costs (in-hospital and out-of-hospital costs, supportive care costs) and direct non-medical costs (transportation and sick leave costs) were calculated by using a cost-of-illness analysis based on a bottom-up approach. Resources consumed were recorded in situ for each patient, using a prospective direct observation method. RESULTS: Data from 604 patients were analyzed. Median direct medical costs of 1 year of management after diagnosis in operable BC patients were 12,250. Factors independently associated with higher direct medical costs were: diagnosis on the basis of clinical signs, invasive cancer, lymph node involvement and conventional hospitalization for surgery. Median sick leave costs were 8,841 per patient and per year. Chemotherapy was an independent determinant of sick leave costs (3,687/patient/year without chemotherapy versus 10,706 with chemotherapy). Forty percent (n = 242) of patients declared additional personal expenditure of 614/patient/year. No drivers of these costs were identified. CONCLUSION: Initial stage of disease and the treatments administered were the main drivers of direct medical costs. Direct non-medical costs essentially consisted of sick leave costs, accounting for one-half of direct medical costs for working patients. Out-of-pocket expenditure had a limited impact on the household.
Sujet(s)
Tumeurs du sein/économie , Coûts des soins de santé , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Tumeurs du sein/thérapie , Coûts indirects de la maladie , Programme clinique/économie , Femelle , France , Coûts hospitaliers , Humains , Adulte d'âge moyen , Programmes nationaux de santé , Études prospectivesRÉSUMÉ
BACKGROUND: Although improved during the last decades, the prognosis of lung cancer is poor. In 2000, the French College of general hospital respiratory physicians, conducted KBP-2000-CPHG, a prospective multicenter epidemiological study including all volunteer adult patients diagnosed for primary lung cancer; with the five-year survival as primary endpoint. The primary objective of KBP-2010-CPHG was to compare overall five-year survival data with KBP-2000-CPHG ones. MATERIAL AND METHODS: All consecutive patients≥18 years of age with primary lung cancer diagnosed between 1st January and 31st December 2010 were included. The KBP-2010-CPHG protocol was approved by the advisory committee on research information processing in the health field (CCTIRS) on November 19, 2009. RESULTS: Respectively, 5667 and 7051 patients were included in KBP-2000-CPHG and KBP-2010-CPHG. Five-year survival was improved: 12.7% [11.9%-13.5%] in 2010 versus 10.0% [9.2%-10.9%] in 2000 (P<0.001). Non-small-cell lung cancer showed improvement (13.8% [13.0%-14.8%] in 2010 versus 11.4% [10.5%-12.4%] in 2000; P<0.001); but not small-cell lung cancer (5.7% [4.4%-7.4%] in 2010 versus 3.3% [2.3%-4.7%] in 2000; P=0.56). The KBP-2010-CPHG study showed an overall 6% reduction in risk of death (HR=0.94 [0.89-0.98]; P=0.004). CONCLUSIONS: Survival of patients with lung cancer improved over a 10-year period. This improvement was slight and limited to non-small-cell lung cancer, possibly partly because of 2010 advances in diagnosis and targeted therapy.