Genomic signature to guide adjuvant chemotherapy treatment decisions for early breast cancer patients in France: a cost-effectiveness analysis

IntroductionChemotherapy (CT) is commonly used as an adjuvant treatment for women with early breast cancer (BC). However, not all patients benefit from CT, while all are exposed to its short- and long-term toxicity. The Oncotype DX® test assesses cancer-related gene expression to estimate the risk of BC recurrence and predict the benefit of chemotherapy. The aim of this study was to estimate, from the French National Health Insurance (NHI) perspective, the cost-effectiveness of the Oncotype DX® test compared to standard of care (SoC; involving clinicopathological risk assessment only) among women with early, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC considered at high clinicopathological risk of recurrence.MethodsClinical outcomes and costs were estimated over a lifetime horizon based on a two-component model that comprised a short-term decision tree representing the adjuvant treatment choice guided by the therapeutic decision support strategy (Oncotype DX® test or SoC) and a Markov model to capture long-term outcomes.ResultsIn the base case, the Oncotype DX® test reduced CT use by 55.2% and resulted in 0.337 incremental quality-adjusted life-years gained and cost savings of €3,412 per patient, compared with SoC. Being more effective and less costly than SoC, Oncotype DX® testing was the dominant strategy.DiscussionWidespread implementation of Oncotype DX® testing would improve patient care, provide equitable access to more personalized medicine, and bring cost savings to the health system

Humoral, T-cell and B-cell immune responses to seasonal influenza vaccine in solid organ transplant recipients receiving anti-T cell therapies

Background: We analyzed the impact of the anti-T-cell agents basiliximab and antithymocyte globu- lins (ATG) on antibody and cell-mediated immune responses after influenza vaccination in solid-organ transplant recipients. Methods: 71 kidney and heart transplant recipients (basiliximab [n = 43] and ATG [n = 28]) received the trivalent influenza vaccine. Antibody responses were measured at baseline and 6 weeks post-vaccination by hemagglutination inhibition assay; T-cell responses were measured by IFN-)' ELISpot assays and intra- cellular cytokine staining (ICS); and influenza-specific memory B-cell (MBC) responses were evaluated using ELISpot. Results: Median time of vaccination from transplantation was 29 months (IQR 8–73). Post-vaccination seroconversion rates were 26.8% for H1N1, 34.1% for H3N2 and 4.9% for influenza B in the basiliximab group and 35.7% for H1N1, 42.9% for H3N2 and 14.3% for influenza B in the ATG group (p = 0.44, p = 0.61, and p = 0.21, respectively). The number of influenza-specific IFN-)'-producing cells increased significantly after vaccination (from 35 to 67.5 SFC/106 PBMC, p = 0.0007), but no differences between treatment groups were observed (p = 0.88). Median number of IgG-MBC did not increase after vaccination (H1N1, p = 0.94; H3N2 p = 0.34; B, p = 0.79), irrespective of the type of anti-T-cell therapy. Conclusions: After influenza vaccination, a significant increase in antibody and T-cell immune responses but not in MBC responses was observed in transplant recipients. Immune responses were not significantly different between groups that received basiliximab or ATG

Global Evaluation of Early Breast Cancer Patients' Management : Medico-Economic Analysis of Clinical Pathway, Quality of Care, Evaluation of Patients Satisfaction and Impact of New Technologies on Treatment Decisions

Le cancer du sein est une pathologie fréquente mais hétérogène. Il existe ainsi de multiples parcours de santé, dont l’optimisation est un des objectifs du 3ème Plan Cancer. Les parcours de santé ont été analysés sous 3 aspects : qualité, coût et impact psychosocial, à travers 2 études prospectives multicentriques. Des leviers d’efficience ont été identifiés : favoriser le dépistage du cancer du sein, s’inspirer de l’organisation des centres de lutte contre le cancer, mieux cibler les patientes tirant bénéfice d’une chimiothérapie adjuvante par l’accès à des outils innovants tels que les tests génomiques. Dans une 3ème étude prospective, la décision de chimiothérapie adjuvante était modifiée dans 18% des cas. La génomique entre en routine en sénologie. Les cliniciens doivent comprendre cette discipline. La dernière partie de cette thèse rapporte les travaux menés en génomique dans le cancer du sein, au stade de la recherche sur un gène codant pour une protéine à activité méthyltransférase, PRDM15, prometteuse dans les cancers du sein triple négatif exprimant les récepteurs aux androgènes.Breast cancer is a frequent but heterogeneous disease. Therefore, there are multiple clinical pathways, of which the optimization is one of the objectives of the 3rd Plan Cancer. Three dimensions of the clinical pathways were analyzed through 2 multicenter prospective studies: quality, cost and psychosocial impact. Efficiency levers have been identified: to promote screening for breast cancer, to mimic the organization of comprehensive cancer centers, to better target patients benefiting from adjuvant chemotherapy by accessing tools innovations such as genomic tests. In a 3rd prospective study, the adjuvant chemotherapy decision was modified in 18% of the cases. Genomics enters routine in oncology. Clinicians must understand this discipline. The last part of this thesis reports the work carried out in genomics in breast cancer, at the stage of research on a gene coding for a protein with methyltransferase activity, PRDM15, promising in triple-negative breast cancers expressing androgen receptors

Facteurs de décision de non-reconstruction du sein chez 1937 patientes ayant eu une mastectomie pour cancer à l'Institut Curie

Objectif: Déterminer les facteurs de décision de non-reconstruction et évaluer la qualité de l'information chez les patientes ayant eu une mastectomie pour cancer du sein. Patientes et méthodes: Etude rétrospective (n=1937) : comparaison des facteurs clinico- biologiques des patientes mastectomisées reconstruites et non reconstruites. Questionnaire adressé à 10% des patientes non reconstruites (n= 132). Résultats: Taux de non reconstruction: 68 % . Facteurs associés à une non reconstruction (analyse multivariée, pI, absence de tabagisme actif, traitement par radiothérapie, surexpression de HER 2, état métastatique. La non reconstruction est un choix personnel dans 80 % des cas. Information jugée comme absente ou insuffisante dans 62 % des cas. Conclusion: Les causes de non reconstruction sont liées aux pronostics du cancer, au mode de vie des patientes et le plus souvent à un choix personnel.Purpose: To determinate clinico-biologic factors associated to no breast reconstruction after mastectomy for breast cancer and to evaluate information quality. Patients and methods: Retrospective study (n= 1937) : comparison of clinico-biologic factors of patients who had a reconstruction to them who didn't have. Analysis of a questionnaire sent to a 10 % of patients with no reconstruction (n= 132). Results: Rate of no (Çconstruction was 68%. Factors associated to no breast reconstruction (multivariate analysis, p l, absence of smoking, radiotherapy treatment, overexpression of HER2, metastatic status. No reconstruction is a personal choice in 80 %. Information considered as absent or deficient in 60% of the patients. Conclusion: Reasons of no reconstruction are linked to cancer prognostic, patient' s characteristics and ways of live but also to personal choice.PARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

Hystérectomie de clôture dans les cancers du col localement avancés (morbidité, pertinence de l IRM pour le diagnostic du résidu tumoral et survie)

Introduction : Le traitement de référence pour les cancers du col localement avancés (stades IB2 à IVA) consiste en une radio-chimiothérapie concomitante (RCC). La chirurgie de clôture est controversée à cause de son bénéfice non démontré et de sa morbidité. Les objectifs de cette étude étaient d évaluer la morbidité de l hystérectomie de clôture, la pertinence de l IRM pour la détection d un résidu tumoral et la survie. Patientes et méthodes : Cette étude rétrospective multicentrique a inclus, entre 2006 et 2012, 159 patientes ayant eu un cancer du col localement avancé traité par RCC et chirurgie de clôture. Une IRM pelvienne était réalisée après la RCC. L étude a porté sur les complications, les résultats de l IRM et l analyse anatomopathologique, la survie. Résultats : L hystérectomie de clôture était élargie dans 67,9% des cas. Un résidu histologique était présent chez 45,3% des patientes. Il n y a eu aucun décès suite à la chirurgie. Seize patientes ont eu une complication de grade >= 2 selon la classification de Chassagne (10,1%). Huit patientes (5,0%) ont eu une fistule urinaire. Un délai de plus de 8 semaines entre la fin de la RCC et la chirurgie était corrélé à une réduction du taux de complications (p=0,009). Le taux de faux positifs à l IRM était de 29,2% et le taux de faux négatifs de 11,1%. La survie globale (SG) à 1 et 5 ans était respectivement de 93% (IC 95% [88,9%-97,3%]) et 76,5% (IC 95% [68,2%-85,7]). La SSR était réduite en cas de résidu tumoral de plus de 10 mm (HR=4,84 ; p=0,03). Conclusion: Notre étude montre un taux de complications relativement faible de l hystérectomie de clôture. La détection d un résidu doit être améliorée et une étude prospective comparant la chirurgie de clôture avec l abstention est nécessaire pour évaluer le bénéfice de celle-ci en termes de surviePARIS12-Bib. électronique (940280011) / SudocSudocFranceF

Has tumor doubling time in breast cancer changed over the past 80 years? A systematic review

International audienceOver the past century, epidemiologic changes and implementation of screening may have had an impact on tumor doubling time in breast cancer. Our study was designed to evaluate changes in tumor doubling time in breast cancer over the past 80 years. A systematic review of published literature and meta-regression analysis was performed. An online electronic database search was undertaken using the PubMed platform from inception until June 2020. All studies that measured tumor doubling time in breast cancer were included. A total of 151 publications were retrieved. Among them, 16 full-text articles were included in the qualitative analysis. An exponential growth model was used for quantitative characterization of tumor growth rate. Tumor doubling time has remained stable over the past 80 years. Recent studies have not only identified “fast growing tumor” (grade 3, human epidermal growth factor receptor 2-positive, triple-negative, or tumor with an elevated Ki-67) but also “inactive breast cancer” feeding the ongoing debate of overdiagnosis due to screening programs. The stability of tumor doubling time over the past 80 years, despite increasing and changing risk factors, supports the validity for our screening guidelines. Prospective studies based on more precise measurement of tumor size and adjustment for tumor characteristics are necessary to more clearly characterize the prognostic and predictive impact of tumor doubling time in breast cancer

Multidimensional impact of breast cancer screening: Results of the multicenter prospective optisoins01 study.

Breast cancer (BC) screening has been developed to detect earlier stage tumors associated with better prognosis. The aim of study was to evaluate the impact of BC screening on therapeutic management of patients with first operable BC, and on costs, patients' needs, and working life. OPTISOINS01 was a multicenter, prospective observational study which aimed to identify the main care pathway of early BC. Among patients aged from 50 to 74 years-old, 2 groups were defined: the "Clinical signs" group and the "Screening" group (national organized screening and individual screening). We compared between these 2 groups: locoregional and systemic treatments, direct medical and non-medical costs from a National Health Insurance perspective, patients' needs assessed by the validated SCNS-BR8 "breast cancer" module of the SCNS-SF34 supportive care needs survey and the duration of sick leave. The "Clinical signs" group included 89 patients, while the"Screening" group included 290 patients. More axillary lymph node dissections and radical breast surgery were performed in the "Clinical signs". The rate of adjuvant chemotherapy was dramatically higher in the "Clinical signs" group. The median direct medical costs of the "Screening" group were €11,860 (€3,643-€41,030) per year and per patient, much lower than in the "Clinical signs" group (€14,940; €5,317-€41,070). Finally, needs specifically assessed by the SCNS-BR8 questionnaire were significantly higher for the postoperative and post-adjuvant periods in the "Clinical signs" group. This study highlighted the benefit of BC screening in terms of reduced therapies and positive impact on work and social life

Impact of axillary dissection in women with invasive breast cancer who do not fit the Z0011 ACOSOG trial because of three or more metastatic sentinel lymph nodes

International audienceAim The objective of this study was to determine the effects of axillary lymph node dissection (ALND) versus sentinel lymph node biopsy alone (SLNB) on the survival of patients with 3 or more metastatic lymph nodes (MLN) in invasive breast cancer. Methods Data of 9521 patients with invasive T1-2M0 breast carcinoma and initial treatment with SLNB completed or not by ALND and 3 or more MLN were extracted from the SEER database. Univariate and multivariate analyses were performed. Results Overall, 9521 patients were included in the study. SLNB-alone compared with ALND did not result in different overall survival (OS) or specific survival (SS) for patients with 3 or more MLN (p = 0.46 and 0.58, respectively). In subgroup analyses, OS was comparable between SLNB-alone and ALND when patients had only 3 or more than 3 MLN. When patients had 3 MLN, the 5-year SS was significantly better for patients with ALND compared with SLNB-alone: 91.5% and 85.1%, respectively (p = 0.02). The Hazard Ratio (HR) for OS comparing SLNB-alone with ALND adjusting for age, adjuvant radiotherapy, tumor size, estrogen receptor status, grade and tumor type resulted in an HR of 1.05 (95% CI, 0.72-1.54, p = 0.77). Conclusion In conclusion, patients with a T1-T2 invasive breast cancer and at least 3 MLN do not benefit from ALND after SLNB for specific and overall survival, thus limiting ALND to a staging procedure. A subgroup of patients with 3 MLN had a better SS with ALND, possibly due to an under-staging of the SLNB-alone group

Delayed hysteroscopic resection of retained tissues and uterine conservation after conservative treatment for placenta accreta

International audienceBackgroundConservative management of both the uterus and the abnormal placenta, which is left inside the uterus at the time of delivery, is one option of placenta accreta management. Complete elimination of the residual placenta is the main challenge of this procedure.AimTo report the role, efficacy and safety of hysteroscopic resection in women presenting with severe pelvic pain and chronic intra-uterine retention after conservative treatment of placenta accreta.Material and methodsFour consecutive women who were treated with hysteroscopic resection of retained tissues after conservative treatment of placenta accreta or percreta at the time of delivery. Clinical files and surgical procedures were reviewed. All procedures were performed because of chronic pelvic pain and the absence of a complete spontaneous placental elimination.ResultsAll procedures were successful and uneventful. The uterus was conserved with a complete disappearance of the symptoms in the four women, and two of them became pregnant.ConclusionHysteroscopic resection seems effective and safe for shortening the duration of placental elimination after conservative treatment in women with severe pelvic pain due to uterine retention. This approach allows conserving the uterus and future fertility

Impact of neoadjuvant chemotherapy on the rate of bowel resection in advanced epithelial ovarian cancer

International audienceAim: To assess the decrease in the number of bowel resections (BR) necessary to achieve complete cytoreduction (CC-0) in advanced epithelial ovarian cancer (EOC) permitted by neoadjuvant chemotherapy (NAC). Patients and Methods: Patients were selected from a population of advanced EOC cases diagnosed between 2002 and 2009 at the Curie Institute: 97 patients with Federation International of Gynecology and Obstetrics IIIc and IV with unresectable disease treated with NAC followed by interval debulking surgery were included. We proceeded to a systematic blinded review of all the surgical reports pre-and post-NAC by two different surgeons to assess the surgical procedures required to obtain CC-0. Results: Before NAC, at least 84 patients (87%) would have required BR to obtain a CC-0 resection. At interval debulking surgery, 47 (49%) still required a BR, which corresponds to a decrease of 38% (p<0.0001). The same decrease was observed for resection of small bowel, colon and rectosigmoid, as follows: 54 to 17 (77% to 24%, p<0.0001), 45 to 19 (56% to 24%, p<0.0001) and 72 to 25 (90% to 31%, p<0.0001), respectively. The median overall survival (OS) among CC-0 patients with and without BR was 57 months [95% confidence interval (CI)=25-90 months] and 50 months [95% CI=43-57 months], respectively (p=0.71). The OS among patients without complete resection was significantly worse, with a median of 21 months (95% CI=17-32 months, p<0.0001). Conclusion: NAC significantly reduces the need and rate of BR in advanced EOC, but also of small bowel, colon and rectosigmoid resection. There is no loss of OS, after BR especially if the debulking surgery is comple