Papers by Bernard Asselain
The PACS 01 trial compared six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) wit... more The PACS 01 trial compared six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) with a sequential regimen of three cycles of FEC followed by three cycles of docetaxel (FEC-D) as adjuvant treatment for women with node-positive early breast cancer. Between June 1997 and March 2000, 1,999 patients with operable node-positive breast cancer were randomly assigned to either FEC every 21 days for six cycles, or three cycles of FEC followed by three cycles of docetaxel, both given every 21 days. Hormone-receptor-positive patients received tamoxifen for 5 years after chemotherapy. The primary end point was 5-year disease-free survival (DFS). Median follow-up was 60 months. Five-year DFS rates were 73.2% with FEC and 78.4% with FEC-D (unadjusted P ϭ .011; adjusted P ϭ .012). Multivariate analysis adjusted for prognostic factors showed an 18% reduction in the relative risk of relapse with FEC-D. Five-year overall survival rates were 86.7% with FEC and 90.7% with FEC-D, demonstrating a 27% reduction in the relative risk of death (unadjusted P ϭ .014; adjusted P ϭ .017). The incidence of grade 3 to 4 neutropenia, the need for hematopoietic growth factor, and incidence of nausea/vomiting were higher with FEC. Docetaxel was associated with more febrile neutropenia in the fourth cycle, stomatitis, edema, and nail disorders. Though rare overall, there were fewer cardiac events after FEC-D (P ϭ .03), attributable mainly to the lower anthracycline cumulative dose. Sequential adjuvant chemotherapy with FEC followed by docetaxel significantly improves diseasefree and overall survival in node-positive breast cancer patients and has a favorable safety profile.
Background: Circulating tumor DNA (ctDNA) has been proposed as a biological surrogate of the repe... more Background: Circulating tumor DNA (ctDNA) has been proposed as a biological surrogate of the repertoire of molecular aberrations in cancer patients. The genetic information derived from the analysis of ctDNA may be therefore employed as biomarker for diagnosis, prognostication, therapy response monitoring and assessment of genetic mechanisms of resistance. We have initiated a prospective study in a population of BRCA1-mutation carrier at high risk of either relapse and/or new cancer growth. The CirCA01 study is based on the combination of (i) on the clinical side, the systematic inactivation of the TP53 gene by mutations in BRCA1-related cancers, whatever the histological type and the organ of origin, and (ii) on the bench side, an original assay that allows to detect any TP53 mutation in plasma with exquisite sensitivity. Methods: CirCA01 is a national prospective study, opened in several cancer centers in France (Institut Curie, Gustave Roussy, Centre Leon Berard, Centre Eugene Marquis) and funded by the French Ministry of Health (PHRCK1369250N). Inclusion criteria are: patients with no evidence of any invasive tumor mass at inclusion (clinical and, if any, radiological exams), carriers of known germline BRCA1 deleterious mutation (a personal history of cancer being not mandatory), age ≥ 30 years for patient with previous history of cancer or age ≥ 40 years for patient without previous history of cancer, written informed consent. Main exclusion criteria are: patient presenting with invasive tumor masses (e.g. stage IV cancer or localized cancer not yet surgically removed), carriers of germline BRCA1 variant of unknown significance, carriers of germline BRCA2 deleterious mutation or variant, individuals with a low risk of BRCA1 -related tumor growth, i.e. women who underwent prophylactic bilateral mastectomy, annexectomy or controlateral prophylactic mastectomy after breast cancer. 200 BRCA1 mutation carriers will be enrolled and followed up regularly, as per national guideline for high-risk patients. Fresh plasma samples will be collected at each follow-up visit to the hospital and will be used to detect any mutation in TP53 exons and flanking non-translated regions by a "digital NGS"-based technique. (NCT registration ongoing). Results: Correlation with patients outcome will allow to report whether TP53 ctDNA detection may be used as (i) a new screening test that can be repeated easily in BRCA1-carriers with no evidence of tumor growth (ii) a new diagnostic test in BRCA1-carriers who present a clinical or radiological abnormality (typically ACR class 3 mammograms): (A) diagnosis of the malignant vs benign nature of the abnormality, based on TP53 mutation levels, (B) differential diagnosis of a new cancer growth vs relapse of a previously treated cancer based on TP53 mutation characterization (different vs similar TP53 mutations). Citation Format: Francois-Clement Bidard, Dominique Stoppa-Lyonnet, Catherine Nogues, Olivier Caron, Suzette Delaloge, Catherine Dugast, Christine Lasset, Frederique Berger, Bernard Asselain, Olivier Lantz, Marc-Henri Stern, Jean-Yves Pierga. TP53 mutants in circulating tumor DNA and follow-up of BRCA1 mutation carriers: The CirCA01 study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-2-04.
BMC Research Notes, Nov 3, 2010
Background: The increasing number of methodologies and tools currently available to analyse gene ... more Background: The increasing number of methodologies and tools currently available to analyse gene expression microarray data can be confusing for non specialist users. Findings: Based on the experience of biostatisticians of Institut Curie, we propose both a clear analysis strategy and a selection of tools to investigate microarray gene expression data. The most usual and relevant existing R functions were discussed, validated and gathered in an easy-to-use R package (EMA) devoted to gene expression microarray analysis. These functions were improved for ease of use, enhanced visualisation and better interpretation of results. Conclusions: Strategy and tools proposed in the EMA R package could provide a useful starting point for many microarrays users. EMA is part of Comprehensive R Archive Network and is freely available at .
British Journal of Cancer, Jun 1, 2015
Background: Recent studies have indicated the prognostic value of tumour subtype and pathological... more Background: Recent studies have indicated the prognostic value of tumour subtype and pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However these results were reported after a short follow-up and using a standard Cox model which could be unsatisfactory for time-dependent factors. In the present study, we identified the prognostic factors for long-term outcome after NAC, considering that they could have an inconstant impact over time. Methods: Prognostic factors from 956 consecutive breast cancer patients treated with NAC were identified and associated with long-term outcomes. We estimated survival by a time function multivariate Cox model regression and stratified by follow-up length. Results: The prognostic value of tumour histological grade and hormone receptors status varied as distant recurrence-free interval (DRFI) increased. The multivariate analysis identified the following significant prognostic factors: tumour size, N stage, clinical and pathological response to NAC, hormone receptors (HR) status and histological tumour grade. The 'prognostic benefit' of lowgrade and positive-HR status decreased over the years. Thus, in the early years after cancer diagnosis, the hazard ratio of distant recurrences in patients with positive-HR status increased from 0.26 (95% CI 0.1-0.4) at 6 months to 2.2 (95% CI 1.3-3.7) at 120 months. The histological tumour grade followed a similar trend. The hazard ratio of grade III patients compared with grade I was 1.83 (95% CI 1.1-2.8) at 36 months and diminished over time to 0.70 (95% CI 0.4-1.3) at 120 months. This indicates that the risk of recurrence for positive-HR patients was 74% lower at 6 months compared with the negative-hormone receptor group, but 30% higher at 5 years and more than double at 10 years. High-grade tumours presented a risk of 83% in the earlier years decreasing to 30% at 10 years versus the low-grade group. From the present study, we conclude the importance of identifying time-dependent prognostic factors. Distant recurrence-free interval within women who receive NAC are influenced by achieving pCR and breast cancer subtype. Tumours with more aggressive biology have poorer survival during the first 5 years, but if they exceed this point their prognostic impact is no longer significant. Conversely, positive-HR patients remain at risk for distant recurrence for many years.
Investigative Ophthalmology & Visual Science, 2013
Gynecologic Oncology, 2020
Journal of Clinical Oncology, 2007
21128 Background: Molecular markers (GEP, p53 mutations,) could overcome usual predictors (size, ... more 21128 Background: Molecular markers (GEP, p53 mutations,) could overcome usual predictors (size, pathology, Hormone receptors, HER2) in identifying patients (pts) experiencing complete pathological response (pCR) with anthracyclin based chemotherapy (Clin.Cancer Res., 2004, 10 6789). We aimed at validating and refining these finding in pts treated with ECD. Methods: From 05/2004 to 04/2006 170 pts not amenable to Breast Conserving Therapy and/or with high evolutive potential were randomly allocated to EC (75/750mg/sqm)x4 then D (100 mg/sqm)x 4 (with or without celecoxib in HER2-ve or trastuzumab (T) in HER2+ve. The primary endpoint - absence of residual invasive breast carcinoma and of nodal involvement (pCR)- was to be correlated with usual predictors , phenotype, GEP and p53 mutations assessed from core biopsies. pCR ranged from 13 to 14% in the arms without T thus without suggestion of a difference between these arms. pCR in the 30 HER2+ve pts having received ECD + T was 30% (NS)...
OncoImmunology, 2019
Immunosurveillance plays an important role in breast cancer (BC) prognosis and progression, and c... more 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 tumorinfiltrating 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 drugrepositioning strategies to improve the efficacy of NAC in BC.
Journal of Clinical Oncology, 2016
1013Background: In 2014, UNICANCER (composed of 18 French Comprehensive Cancer Centers) launched ... more 1013Background: In 2014, UNICANCER (composed of 18 French Comprehensive Cancer Centers) launched the Epidemiological Strategy and Medical Economics (ESME) program to centralize real-world data in oncology. Metastatic breast cancer (mBC) was first selected to address the value of bevacizumab (B) added to paclitaxel (P) as first-line chemotherapy (CT) for HER2-negative tumours, while randomized trials have led to mixed results on outcome. Methods: The ESME-mBC database was built from information systems, treatment databases and patients’ electronic files including quality control processes. All patients who started a first-line anti-cancer treatment for mBC between 01-Jan-2008 and 31-Dec-2013 were selected. The primary objective of the present study was to assess overall survival (OS) in patients with HER2-mBC treated with a first-line P-based CT ± B. Cox regression with adjustment for the main prognostic covariates was used to estimate the hazard ratio (HR) for OS and progression-free survival (PFS). To ad...
Cancer Research, 2013
Background: T-DM1 has demonstrated its efficacy in the second line of HER2-positive metastatic br... more Background: T-DM1 has demonstrated its efficacy in the second line of HER2-positive metastatic breast cancer patients. Several studies reported that some breast cancers considered as HER2-negative do have HER2-positive circulating tumor cells (CTC). Our previous report (Lightart & Bidard, Ann Oncol 2013) showed that the reliability of such discrepancy between primary tumor and CTC is directly related to the number of CTC analyzed. This study aims at studying the efficacy of T-DM1 in this setting. Trial design: CirCe T-DM1 is a single arm two-step phase II multicenter study with adaptive design. Patients with HER2-negative measurable metastatic breast cancer will be screened by the FDA-approved CellSearch system, before the start of a second line treatment. HER2/CEP17 ratio will be quantified by FISH on CTC (Veridex). Patients with non HER2-amplified CTC or no CTC will be excluded from the study. Patients with HER2-amplified CTC will be treated by T-DM1 (Roche) single agent q3w, in e...
Breast Cancer Research and Treatment, 2016
Use of parametric statistical models can be a solution to reduce the follow-up period time requir... more Use of parametric statistical models can be a solution to reduce the follow-up period time required to estimate long-term survival. Mould and Boag were the first to use the lognormal model. Competing risks methodology seems more suitable when a particular event type is of interest than classical survival analysis. The objective was to evaluate the ability of the Jeong and Fine model to predict long-term cumulative incidence. Survival data recorded by Institut Curie (Paris) from 4761 breast cancer patients treated and followed between 1981 and 2013 were used. Long-term cumulative incidence rates predicted by the model using short-term follow-up data were compared to non-parametric estimation using complete follow-up data. 20-or 25-year cumulative incidence rates for loco-regional recurrence and distant metastasis predicted by the model using a maximum of 10 years of follow-up data had a maximum difference of around 6 % compared to nonparametric estimation. Prediction rates were underestimated for the third and composite event (contralateral or second cancer or death). Predictive ability of Jeong and Fine model on breast cancer data was generally good considering the short follow-up period time used for the estimation especially when a proportion of patient did not experience loco-regional recurrence or distant metastasis.
Revue d'Oncologie Hématologie Pédiatrique, 2014
Resume Le retinoblastome est un cancer rare qui touche principalement les nourrissons et les jeun... more Resume Le retinoblastome est un cancer rare qui touche principalement les nourrissons et les jeunes enfants et qui implique l’œil, organe dont la valeur symbolique est grande. En raison de la brutalite du diagnostic, de l’âge de l’enfant, de l’organe touche, du contexte de predisposition genetique, possible ou certaine, et de la blessure narcissique ressentie par les parents, il apparait important d’evaluer la satisfaction de ces parents vis-a-vis de la prise en charge therapeutique de leur enfant. Dans cette etude, nous avons mene, au moment du diagnostic et un an plus tard, des entretiens semi-directifs avec les parents auxquels nous avons egalement remis des questionnaires visant a evaluer leur ressenti. Trente-huit familles ont participe a l’etude, l’âge moyen des enfants traites etait de 13 mois. La moitie des enfants presentaient un retinoblastome bilateral et, parmi ceux-ci, 76 % avaient subi une enucleation unilaterale. Les resultats montrent que la majorite des parents ont ete satisfaits de la prise en charge, en depit du traumatisme lie au diagnostic et au traitement. Ils mettent en avant l’importance de la disponibilite et de la coherence des equipes pediatriques et ophtalmologiques, la totale confiance dans les medecins « specialistes », meme si les informations recues sont difficiles a integrer, particulierement celles concernant les aspects genetiques. Dans un tel contexte, le soutien psychologique apparait important, tant au moment du diagnostic qu’a l’issue du traitement, pour anticiper l’avenir de l’enfant et son handicap eventuel. Les resultats de cette etude devraient permettre une amelioration de la prise en charge globale des enfants atteints de retinoblastome.
Acta Ophthalmologica, 2014
ABSTRACT Purpose Since 2OOO, we have been using proton beam therapy after surgery for all invasiv... more ABSTRACT Purpose Since 2OOO, we have been using proton beam therapy after surgery for all invasive conjunctival melanomas. Patients with associated primary acquired melanosis also receive additional treatment with mitmycin 0, 04% drops at least two cycles. We have made a retrospective study to evaluate the results.Methods Patients were sent to Curie Institute for initial treatment, after the initial surgery or for recurrence. Surgery was performed under general anesthesia; proton beam was applied only on the area of invasive melanoma with a dose of 60 grays in 8 fractions. Results concerning the initial findings, the treatment and the follow up were prospectively registered.Results 62 patients were treated, 36 for initial treatment and 26 after surgery performed elsewhere. The median follow up is 24 months.(range 7 to 146 months) Median tumor diameter was 8 mm, with a thickness < 2mm for 33, > 2mm for 22 patients. TNM and histology will be described. Surgical excision was considered complete in 21 cases. All patients received proton beam irradiation and 25 received mitomycin drops. 10 patients (16%) presented local recurrence and 4 patients (6%) developed metastatic disease.Conclusion : Because of direct contact with the sclera, invasive conjunctival melanoma cannot be removed with sufficient margin if the eye is not removed. The use of proton beam therapy immediately after surgery allows good ocular preservation with very low rate of local recurrence .The prognostic of patients with primary acquired melanosis with atypia has been improved by the use of preventive treatment of the conjunctiva by mitomycin before invasive melanoma occurs.
Cancer/Radiothérapie, 1997
But de /'etude : Analyse rktrospective des resultats preliminaires du traitement par protons du m... more But de /'etude : Analyse rktrospective des resultats preliminaires du traitement par protons du melanome de la choro'ide au centre de protontherapie d'orsay.
Revue d'Épidémiologie et de Santé Publique, 2005
ABSTRACT Background For pertinent investigation of patient satisfaction it is important to know w... more ABSTRACT Background For pertinent investigation of patient satisfaction it is important to know what type of data collection procedure yields optimal results. In this study, we compared a self- versus interview administration of the European Organisation for Research and Treatment of Cancer (EORTC) patient satisfaction questionnaire (QLQ-SAT32), noting response and item omission rates. We also assessed the correlation and agreement between responses according to these modalities of questionnaire administration. Methods 123 patients recruited in two anti-cancer Centers in France were asked to complete the QLQ-SAT32 at home within 2 weeks of hospital discharge and were randomly allocated to participate in a telephone interview-administration of the QLQ-SAT32, either before or after self-completing the QLQ-SAT32. Results 104 patients completed both modalities of questionnaire administration. Agreement proved excellent for the doctors’ and nurses’ subscales and satisfactory for the services’ subscale and the general satisfaction single item. However, a significant difference in response rate showed up between Centers (different interviewers) and the interview modality revealed an item omission rate higher than for the self-administration modality. Conclusion Self- and interview-administration of the QLQ-SAT32 provided similar responses however different response rate between interviewers and higher item omission rate in interviews suggests a biasing effect of that modality of data collection.
Cancer/Radiothérapie, 2013
Objectif.-Évaluer les résultats à long terme de la protonthérapie du mélanome de la choroïde au c... more Objectif.-Évaluer les résultats à long terme de la protonthérapie du mélanome de la choroïde au centre de protonthérapie de l'institut Curie. Méthode.-Tous les patients ont rec ¸u une dose de 60 Gy (EBR) en quatre séances de 15 Gy (EBR) en prenant une marge de sécurité de 2,5 mm autour du volume tumoral. Le logiciel Eyeplan a été utilisé pour la dosimétrie. Les taux de survie ont été calculés selon la
Patient Education and Counseling, 2004
Doubts are expressed on the validity of patient satisfaction questionnaires. High satisfaction le... more Doubts are expressed on the validity of patient satisfaction questionnaires. High satisfaction levels are consistently reported. Within the European Organisation for Research and Treatment of Cancer (EORTC) quality of life group, we developed a cancer inpatient satisfaction questionnaire (QLQ-SAT32), adopting several precautions to overcome the ceiling effect commonly reported in satisfaction ratings. Since patients are often more critical when expressing themselves in an interview, in order to study the validity of the QLQ-SAT32, we assessed the agreement between self-and interview-administered QLQ-SAT32 responses. One hundred and twenty three patients were asked to complete the QLQ-SAT32 at home within 2 weeks of hospital discharge and were randomly allocated to participate in a telephone interview-administration of the QLQ-SAT32, either before or after self-completing the QLQ-SAT32. One hundred and four of them completed both modalities of questionnaire administration. Correlation and agreement between self-and interview-administered QLQ-SAT32 ratings were examined, for each subscale and the general satisfaction item of the QLQ-SAT32, using Spearman correlation, intra-class correlation coefficients (ICC) or weighted kappa coefficients. Agreement showed excellent for the doctors' and nurses' subscales and satisfactory for the services' subscale and the general satisfaction single item. The telephone interview-administration modality did not prove an adequate procedure to assess the validity of a patient satisfaction questionnaire.
Ophthalmic Research, 2006
Introduction: Exudation from the tumour scar and glaucoma can be major problems after proton beam... more Introduction: Exudation from the tumour scar and glaucoma can be major problems after proton beam irradiation of uveal melanoma and can sometimes lead to secondary enucleation. We conducted a randomized study to determine whether systematic transpupillary thermotherapy (TTT) after proton beam radiotherapy could have a beneficial effect. Patients and Method:Between February 1999 and April 2003, all the patients treated by proton beam radiotherapy for uveal melanomas ≧7 mm thick or ≧15 mm in diameter were included in this study after giving their informed consent. One half of the patients received proton beam radiotherapy alone (60 Gy in 4 fractions) and the other half received the same dose of proton beam radiotherapy followed by TTT at 1, 6 and 12 months. All the information concerning the initial tumour parameters, treatments and follow-up was recorded and a statistical analysis was performed. Results: We randomized 151 patients. The median follow-up was 38 months. The 2 groups of ...
Journal Français d'Ophtalmologie, 2005
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Papers by Bernard Asselain