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ROMANCE ESSAI D'ABSTENTION DE RADIOTHÉRAPIE MAMMAIRE DANS LES CARCINOMES CANALAIRES IN SITU DU SEIN À FAIBLE RISQUE DE RÉCIDIVE, APRÈS CHIRURGIE CONSERVATRICE A. FOURQUET Eligibility Criteria INCLUSION Femmes ≥ 55 ans, ménopausées Carcinome canalaire in situ strict, confirmé CCIS découvert incidemment sur biopsie ou chirurgie d’une lésion bénigne Grade nucléaire bas ou intermédiaire Microcalcifications mammographiques Unifocalité confirmée par IRM Chirurgie conservatrice Berges saines d’emblée (≥ 2 mm), ou après ré-excision pT < 25 mm Pas de microcalcifications résiduelles sur une mammographie post-opératoire Profil IHC confirmé par évaluation centralisée, associant: RO ≥ 10 % RP ≥ 10 % ERBB2 – (confirmé par FISH si douteux) KI67 < 15% EXCLUSION Age < 55 ans Prédisposition génétique Tumeur palpable, opacité, écoulement mamelonnaire sanglant Multifocalité Berges atteintes Cancer microinvasif ou invasif associé Grade nucléaire élevé Microcalcifications résiduelles Traitement endocrinien programmé Objectives PRIMARY OBJECTIVE Déterminer si une utilisation combinée de marqueurs cliniques, histologiques et immunohistochimiques peut identifier un groupe de patientes à très faible risque de récidive locale, pour lesquelles une radiothérapie du sein après chirurgie conservatrice pourrait être omise SECONDARY OBJECTIVES Pronostic des récidives locales Evaluation des séquelles et du résultat esthétique Mesure de la qualité de vie Valeur pronostique des TIL dans les CCIS Validation d’une signature génomique prédictive Analyse médico-économique Schéma de l’étude 323 patients dans chaque bras (700 au total), 3 ans d’inclusion, 10 ans de suivi LORD LOW RISK DCIS R. ROUZIER Eligibility Criteria INCLUSION DCIS, grade I, on vacuum assisted core biopsy, as confirmed by at least double reading TisNxMx Referral to the hospital solely based on microcalicifications as detected by mammogram by the national screening program or by opportunistic screening Radiology studies (mammogram and ultrasound performed within 28 days prior to registration) confirming results found at screening BEFORE RANDOMIZATION • • • • ≥ 5 vacuum assisted core biopsies with pure low grade DCIS Marker placement at biopsy site MRI unsuspicious of invasive breast cancer or higher grade DCIS Good correlation between radiological and pathological findings, i.e. both findings confirm low grade DCIS and no suspicion of intermediate or high grade DCIS or invasive breast cancer EXCLUSION Bilateral grade I DCIS Paget’s disease of the nipple on core biopsy Women Invasive breast disease on core biopsy ≧49 years of age LCIS on core biopsy Patient‘s life expectancy > 5 years Prior history of contralateral DCIS allowed Prior surgery of the ipsilateral breast because of a benign lesion allowed Symptomatic DCIS Serious non-malignant disease that precludes definitive surgical treatment Prior history of cancer, except adequately treated non-melanocytic skin cancer and carcinoma in situ of the cervix Synchronous invasive carcinoma of the contralateral breast cancer BRCA1/2 Objectives PRIMARY OBJECTIVE To determine whether low- grade DCIS can safely (measured by ipsilateral invasive breast cancer rate at 10 years) be managed by an active surveillance strategy or if the conventional treatment, being either wide local excision (WLE) only, WLE plus radiotherapy or mastectomy, possibly followed by hormonal therapy, will remain the standard of care. MAIN SECONDARY OBJECTIVES To assess the rate of invasive disease at final pathology specimen in the standard treatment arm. To assess the rate of higher grade DCIS at final pathology specimen in the standard treatment arm. To assess the biopsy rate during follow-up in the standard treatment and active surveillance arm. To compare the ipsilateral mastectomy rate between the two therapeutic policies. … Study Design • 1842 patients (taking into account 5% dropout at 10 years and 5% ineligible) • Accrual duration of 5.5 years and an further follow up period of 7.5 years • Total study duration ≈ 13 years, median follow-up duration: 10 years. HYPOCIS ETUDE RANDOMISÉE MULTICENTRIQUE DE PHASE III ÉVALUANT LA RADIOTHÉRAPIE ADJUVANTE HYPOFRACTIONNÉE DU SEIN DANS LES CARCINOMES CANALAIRES IN SITU G. LOUVEL Critères d’éligibilité INCLUSION Femme ≥ 18 ans Carcinome canalaire in situ histologiquement prouvé sans composante infiltrante Traité par chirurgie conservatrice Exérèse complète : marges ≥ 1 mm, prenant en compte les éventuelles recoupes et 2ème réexcision (à l’exclusion des marges superficielle et profonde si exérèse au contact du fascia pectoral ou de la peau) Sans atteinte ganglionnaire histologique (ganglion sentinelle négatif) ou clinicoradiologique Radiothérapie dans les 12 semaines post chirurgie Patiente affiliée à la sécurité sociale Espérance de vie ≥ 10 ans ATCD de cancer (hors cancer du sein) sans signe de récidive depuis au moins 5 ans, à faible risque de récidive, ATCD de carcinome in situ du col, carcinome baso ou spino cellulaire y compris dans les 5 dernières années EXCLUSION Antécédent de cancer du sein infiltrant ou in situ ipsilatéral ou controlatéral Présence d’une composante infiltrante. Présence d’une atteinte ganglionnaire Traitement nécessitant une mastectomie complète Marge d’exérèse insuffisante < 1 mm Pathologie instable ou systémique (Lupus, sclérodermie) Cancer du sein bilatéral Femme enceinte ou allaitante Patiente incapable de se soumettre au traitement ou au suivi protocolaire Objectives PRIMARY OBJECTIVE Comparer la survie sans récidive locale entre le traitement hypofractionné (15 séances) et le traitement standard (25 séances) SECONDARY OBJECTIVES Survie globale et survie sans récidive Evaluation toxicités aigües et tardives Evaluation cosmétique et qualité de vie Taux de cancer du sein controlaréral Evaluation médico économique du rapport coût-efficacité de la radiothérapie normo versus hypofractionnée Study Design Nombre de patients nécessaires 1200 patients, 600 dans chaque bras, inclusions sur 3 ans avec 3 ans supplémentaires de suivi Carcinome canalaire in situ en exérèse complète Vérification des critères d’inclusion/ non inclusion Consentement éclairé RANDOMISATION Bras standard normofractionné: 50 Gy / 25 fractions 2 Gy / fraction 5 fractions / semaine Bras expérimental hypofractionné: 40 Gy / 15 fractions 2.67 Gy / fraction 5 fractions / semaine MULTI-CENTER PHASE 2 STUDY TO EVALUATE BREASTCONSERVATION THERAPY (BCT) IN MULTIFOCAL BREAST TUMORS (MBT) C. COUTANT Eligibility Criteria INCLUSION EXCLUSION Multifocal breast tumors T1-2 Age <18 years 2 or 3 ductal invasive or ductal carcinoma in situ foci that could not be removed by a wide excision alone and will require two or three excisions as long as it is technically and cosmetically feasible Pregnancy Previous breast radiotherapy Contraindication of adjuvant breast radiotherapy Informed consent given Neoadjuvant hormonotherapy Clinical T4 Lobular invasive (?) chemo or Objectives PRIMARY OBJECTIVE to evaluate efficacy of breast-conservation therapy (BCT) in multifocal breast tumors (MBT) in terms of breast tumour recurrence PRIMARY END POINT breast tumour recurrence rate at 5 years SECONDARY OBJECTIVES The early and late reintervention rate, and then the breast conservation rate (BCR) at 6 months and 5 years ‒ BCR at 6 months reflecting the failure of BCT ‒ BCR at 5 years reflecting disease relapse Longitudinal and other dimensions of health related quality of life Toxicity breast radiotherapy DMFS, OS A tumor bank will be built by collection of each foci specimen. A translational research will be performed by a subsequent study to investigate if MBT disease is issociated with worse biology. Methodology MAIN OBJECTIVE: BREAST TUMOUR RECURRENCE NON RANDOMISED PHASE 2 TRIAL LONG TERM ENDPOINT ONE STEP DESIGN HYPOTHESES: a recurrence rate of 10% is without interest (90% of non recurrence) a recurrence rate of 6% is hoped for (94% of non recurrence) alpha=10%, beta=10% , drop out rate=5% 312 subjects PGS-01 PRÉLÈVEMENT GANGLIONNAIRE SÉLECTIF DANS LE CANCER DU SEIN ASSOCIANT L’EXÉRÈSE D’UN GANGLION AXILLAIRE MÉTASTATIQUE REPÉRÉ PAR NOIR DE CHARBON ET LA BIOPSIE DU GANGLION SENTINELLE E. BARRANGER Objectives PRIMARY OBJECTIVE Compare the rate of pN1 between both strategies SECONDARY OBJECTIVE To evaluate and compare the performance of axillary ultrasound to detect one versus 2-3 positive lymph nodes versus more 3 positive lymph nodes (pN2), To evaluate and compare the axillary recurrence using each strategy, To evaluate and compare the performance of 18F-FDG PET/CT to detect one versus more one metastatic lymph nodes, To evaluate and compare both surgical strategies based on morbidity, Performance of SLNB (experimental group): detection rate, number on SLN per patient, correlation to tattooed lymph node and SLN To evaluate and compare both strategies based on QoL, To evaluate the type of adjuvant therapies administered. Eligibility Criteria INCLUSION Age ≥ 18 years - Invasive breast cancer - Tumor size smaller or equal to 5 cm - Patient candidate for breast conserving surgery + radiation therapy - One axillary positive node proven pre-operatively either fine-needle cytology/biopsy axillary guided by ultrasound or either 18F-FDG PET/CT - Patient accessible for follow up EXCLUSION Metastatic breast cancer Previous malignancy Previous systemic treatment Patient candidate for mastectomy Patient not understanding French Vulnerable patient: pregnant or breastfeeding women, person deprived of freedom by an administrative or judicial decision, person older than 18 being the object of a legal protection measure or outside state to express their consent. Pre-operative diagnosis (cytology or biopsy guided by ultrasound or 18F-FDG PET/CT) of > 1 axillary lymph node metastasis Pre-operative 18F-FDG PET/CT evidence of > 1 axillary lymph node metastasis Patients with psychiatric disorder that compromises their ability to give informed consent for participation in this study Study Design 1000 patientes doivent être randomisées, avec un suivi tous les 6 mois la première année, puis tous les ans pendant 10 ans Information patiente Signature du consentement Bilan initial : Echographie axillaire + cytoponction/biopsie TED-TDM Si éligibilité Inclusion et randomisation Eligible: Critères ACOSOG, 1 N+ axillaire prouvé et absence d’autres ganglions axillaires suspects en TEP-TDM Marquage du ganglion métastatique par noir de charbon Curage axillaire Adénectomie (exérèse ganglion marqué par le noir de charbon) > 2 ganglions métastatiques Echec détection du GS et prélèvement du ganglion sentinelle PALLATIN OPEN-LABEL, MULTICENTER, COHORT STUDY, ASSESSING PALBOCICLIB + LETROZOLE COMBINATION AS ADJUVANT TREATMENT FOR ER+ HER2-, PN0 OR N1MI, INTERMEDIATE RISK (AS ASSESSED BY A GENOMIC TEST) BREAST CANCER T. BACHELOT- S. DELALOGE Eligibility criteria Age > 18 years Performance status, ECOG 0-1 Histologically confirmed adenocarcinoma of the breast pT1 or pT2 pN0 or pN1mi M0 ER-positive by IHC (>10%) Genomic test results as “intermediate” HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish negative (HER2 copy number < 4 and HER2/CEP17 ratio < 2) No previous (neo)adjuvant medical therapy Post-menopausal Objectives PRIMARY OBJECTIVE The primary objective is to show that a combination of letrozole + palbociclib, in the absence of chemotherapy, allows high invasive Disease-free survival (iDFS) at 5 years in intermediate risk ER+ Her2localized breast cancer patients. SECONDARY OBJECTIVE(S) Freedom from recurrence at distant sites at 5 years Short and long-term toxicities 10 years iDFS Overall Survival iDFS in Luminal A and Luminal B subtypes Local relapse-free survival at 5 years Compliance with study treatment Patient-related outcomes: QOL Study Design 1400 patients screened for 700 patients included, inclusion period of 2 years with a FU period of 5 years (10 years extension) All patients accrued will be treated with: • Letrozole continuous administration of 2.5 mg per day orally (1 tab per day) for 5 years • in combination with oral palbociclib 125 mg q1d 3w/4w (4 weeks cycles) administered during 1 year. Local treatment accrual PALBOCICLIB 1 YEAR LETROZOLE 5 YEARS PILOTE THE POST IA LONG TERM ENDOCRINE THERAPY TRIAL P. COTTU Objectives PRIMARY OBJECTIVE To assess the 5y benefit (iDFS/DDFS) of extended endocrine therapy after 5 years of IA SECONDARY OBJECTIVE Recurrence Freedom from recurrence at iDFS/distant sites at 5 years Local relapse-free survival at 5 years 10 years iDFS 5y and 10y Overall Survival Safety Short and long-term toxicities Ancillary studies QoL and PROs, Compliance with study treatment ESR1 ctDNA, CTC, Genetics (polymorphisms) Main Eligibility criteria Age > 18 years ECOG 0-1 Histologically confirmed adenocarcinoma of the breast M0 at baseline ER-positive by IHC (>10%) HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish negative (HER2 copy number < 4 and HER2/CEP17 ratio < 2) PAM50 ROR or EPclin test results available Having received 3/5 years IA Study Design 1700 patientes (risque intermédiare/haut) doivent être randomisées, période d’inclusion de 3 ans 5 ans de traitement + suivi de 5 ans. Stop @5y Low risk @5y post IA Or > 2,5y IA EPclin Or ROR Placebo Interm/high risk ® + 5 y IA PRETTI EVALUATION OF THE EFFICACY OF 18FDG-PET/CT RESPONSEGUIDED NEOADJUVANT CHEMOTHERAPY IN TRIPLE NEGATIVE BREAST CANCERS D. GROHEUX Eligibility Criteria INCLUSION WOMEN AGED ≥ 18 YEARS NEWLY DIAGNOSED INVASIVE EXCLUSION NON OPERABLE, BILATERAL OR METASTATIC BREAST BREAST CANCER STAGE-II (EXCEPT T1 N1) OR STAGE-III PRIMARY BREAST BIOPSY MUST BE AVAILABLE NON METASTATIC, M0 ER AND PR NEGATIVE (< 1% THROUGH IHC) HER2-NEGATIVE BY IHC (SCORE 0 OR 1+) AND/OR FISH/CISH ECOG 0-1 NO PRIOR SYSTEMIC THERAPY FOR THE PRESENT TUMOR CANCER UNCONTROLLED DIABETES. LIMITED BREAST CANCER IMMEDIATELY ACCESSIBLE TO CONSERVATIVE SURGERY AND NOT CANDIDATE FOR NAC PREVIOUS HOMOLATERAL BREAST CANCER, AND/OR CONTRALATERAL BREAST CANCER EXCEPT IF TREATED BY SURGERY +/- RADIATION THERAPY ALONE WITHOUT ANY SYSTEMIC TREATMENT ANY SURGERY WITHIN 4 WEEKS OF START OF STUDY TREATMENT; OR NOT FULLY RECOVERED FROM ANY SIDE EFFECTS OF PREVIOUS PROCEDURES. DIAGNOSIS OF ANY PREVIOUS MALIGNANCY WITHIN THE LAST 5 YEARS, EXCEPT FOR ADEQUATELY TREATED BASAL CELL CARCINOMA, OR SQUAMOUS CELL SKIN CARCINOMA, OR IN SITU CERVICAL CARCINOMA. Objectives PRIMARY OBJECTIVE To assess pathological tumor response to standard versus exploratory treatment in patients with TNBC identified by FDG-PET as poor responders after 2 cycles of neoadjuvant dose-dense EC. SECONDARY OBJECTIVE To evaluate prospectively event free survival (EFS) in each of the randomized treatment arms To prospectively assess Breast Cancer Specific survival rates in both randomized arms as well as in predicted good responders To analyze the biological, molecular, and genetic biomarkers of the primary tumor that, coupled with the metabolic response, could improve early prediction of pCR To evaluate the toxicity and the treatment compliance for each treatment arm To control that the SUVmax cut-offs used to predict pCR and EFS are the optimal cut-offs. Study Design 210 patientes doivent être randomisées, sur une période d’inclusion de 2 ans
