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Introduction: Few data have been reported regarding endocrine therapy (ET) in patients with small pT1a-b ER-postive breast cancer (BC). Thus, we conducted a study to detect possible survival improvements due to ET in such patients. Methods: Our retrospective observational study included 5545 patients with pT1a-b ERpositive BC treated in 15 French centres, excluding patients with HER2-positive status, neoadjuvant chemotherapy, ER-negative status, unknown pN status or in situ BC. We estimated disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) via univariate analysis and multivariate Cox regression. Results: Most patients (80.3%: 4453) received ET and-when compared to those without ET -experienced increases of 2.5% and 3.3% in DFS and 1.9% and 4.3% in RFS after 5 and 7 years of follow-up, respectively, with little difference in OS. In Cox regression analysis, no ET was significantly associated with decreased DFS (hazard ratio, HR = 1.275, p = 0.047, 95% CI[1.003-1.620]) but not OS or RFS in all patients, while in 2363 patients with pT1ab ER-positive grade 2-3 BC, no ET was significantly associated with decreased DFS (HR = 1.502, p = 0.049, 95% CI[1.001-2.252]), but not OS (HR = 1.361, p = 0.272). ET omission was not significantly associated with decreased survival in 3047 patients with pT1a-b ER-positive grade 1 BC. Conclusion: Our results indicate that while ET provided a beneficial impact on survival to patients with pT1a-bN0 ER-positive BC-and especially in those with grade 2-3 tumours-no such impact was observed in grade 1 tumours. Consequently, ET should be discussed with these patients, particularly in those with pT1a grade 1 tumours. 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction: Neoadjuvant chemotherapy (NAC) is proposed for locally advanced breast cancer (LABC) to increase the breast conservative treatment (BCT). In France, mastectomy is the risk-reducing prophylactic surgical strategy only for pre-symptomatic germline BRCA-mutated (gBRCAm) patients. On the other hand, BCT is proposed to all patients following NAC based on clinical response, even for patients do not demonstrating germline BRCA mutation. Moreover, in the case of BRCA mutation, local recurrence risk is higher in the BCT group (23%) vs mastectomy (5%). The aim of this retrospective one-institution analysis is to evaluate if the knowledge of gBRCAm status impact shared surgical decision between surgeons and patients. Patients and methods: Inclusion criteria were: (i) patients treated for unilateral LABC, T2-4, N≥0, M0 by NAC, and (ii) patients who underwent germline BRCA screening. BRCA screening, using targeted next-generation screening, was carried out either during NAC (rapid process) or after surgery. Deleterious mutations were confirmed using Sanger sequencing before passing on the results to the clinical geneticist. Some gBRCAm patients from Olympia clinical trial study were also included. Patients were followed-up over a long term for overall survival (OS), local recurrence (LR) and disease-free recurrence interval (DRFI). Chi-square, Fischer test and T-test and Wilcoxon test were used to generate statistical descriptive analysis. Results: Between 2007 and 2015, 988 women were treated for LABC at our institution. Among them, 151 patients underwent clinical genetic testing for gBRCAm based on these criteria: young age at diagnosis or familial history of breast or ovarian cancer or histological characteristics as grade 2/3, Her2-3+ or basal like. A total of 125 patients were included in the study; 27 patients had germline mutations (MT group) and no mutations were detected in 98 patients (WT). Significant differences between the two groups (MT vs WT) were observed for - Intrinsic tumor subtypes basal like (64.3% vs 42.5%, p=0.0432) - ER are more often negative (21.4% vs 46.8%, p=0.0165). Among the 29 patients who underwent germline screening during NAC and eligible for BCT, all the patients with gBRCAm choose mastectomy (100%). Among the 96 patients with screening mutation after breast cancer treatment, 6 of the 19 patients with gBRCAm had a mastectomy (28%). In the 25 gBRCAm patients, 15 had a BCT and 11 a mastectomy. In the 98 wtBRCA patients, 70 had a BCT and 28 a mastectomy. After a follow-up of 76.8 months of 83 patients with BCT, we observed 9 LR, 7% in the WT group and 30.8% in the MT group. The median delay of disease recurrence is 40.8 months [22-113]. According DRFI and OS, there is not statistically difference between the WT and the MT group, at 3 years and 5 years of follow up. Discussion: In this selected subgroup of patients, gBRCAm rate is higher (21%) than the rate based on familial criteria for BRCA testing (12%). Regarding the rationale for BCT or mastectomy procedure in LABC and pre-symptomatic gBRCAm patients, this study led us to establish mastectomy as the sole risk-reducing strategy surgery procedure for gBRCAm patients. Moreover, 100% gBRCAm patients chose mastectomy; the mastectomy rate was lower when the patient was unaware of their BRCA status (26%). The LR rate was higher in the gBRCAm vs wtBRCA with a statistical difference. In LABC patients with high genetic risk, the knowledge of mutation status could influence patients’ and surgeons’ choice of surgery. In case of gBRCAm status, mastectomy is recommended to decrease LR risk Citation Format: Nicolas Sevenet, Christine Tunon de Lara, Jeanne Leroux, Françoise Bonnet, Marc Debled, Delfine Lafon, Emmanuelle Barouk-Simonet, Marion Fournier, Adeline Petit, Virginie Bubien, Nathalie Quenel-Tueux, Véronique Brouste, Gaëtan MacGrogan. Germline BRCA screening for locally advanced breast cancer treated by neoadjuvant chemotherapy: Defining a subgroup with high rate of mutation and local relapses [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-07-10.

Resume Introduction Chez les femmes considerees a haut risque de cancer du sein, la mastectomie est une alternative a la surveillance rapprochee. La chirurgie mammaire de reduction du risque (CMRR) presente des benefices et des risques, dont l’evaluation est particulierement importante car sa realisation depend du choix de la patiente. L’objectif de cette etude etait d’etudier les pratiques de la CMRR dans un centre francais de lutte contre le cancer et notamment d’evaluer la morbidite et le risque de decouverte fortuite de cancer. Methodes Il s’agit d’une etude retrospective, descriptive s’etendant de 2007 a 2017. Les dossiers de toutes les patientes ayant beneficie d’une CMRR bilaterale ou controlaterale ont ete analyses. Resultats Soixante-dix-neuf patientes ont ete operees sur la periode d’etude dont 58,2 % d’une mastectomie controlaterale. Le critere de recevabilite de la demande de mastectomie etait l’existence d’une mutation genetique dans 86,1 % des cas. Une complication postoperatoire est survenue chez 43,0 % des patientes et une reintervention a ete necessaire dans 72,1 % des cas. A l’analyse anatomopathologique, un cancer a ete decouvert dans 11,4 % des cas ; il s’agissait dans deux cas (2,5 %) d’un carcinome infiltrant de type triple negatif. Discussion La CMRR reste a ce jour la mesure la plus efficace de prevention du cancer du sein en France. Chaque femme doit, avant d’y recourir, etre clairement informee de la balance benefice–risque, en particulier de la forte probabilite de presenter une complication, de la necessite de plusieurs temps operatoires et de l’existence d’un risque de decouvrir un cancer a l’analyse anatomopathologique. L’accompagnement preoperatoire doit etre optimise afin de guider au mieux ces femmes dans leur processus decisionnel.

Objective: This paper presents and evaluates a breast-specific magnetic resonance guided focused ultrasound (MRgFUS) system. A first-in-human evaluation demonstrates the novel hardware, a sophisticated tumor targeting algorithm and a volumetric magnetic resonance imaging (MRI) protocol. Methods: At the time of submission, N = 10 patients with non-palpable T0 stage breast cancer have been treated with the breast MRgFUS system. The described tumor targeting algorithm is evaluated both with a phantom test and in vivo during the breast MRgFUS treatments. Treatments were planned and monitored using volumetric MR-acoustic radiation force imaging (MR-ARFI) and temperature imaging (MRTI). Results: Successful technical treatments were achieved in 80 $\%$ of the patients. All patients underwent the treatment with no sedation and 60 $\%$ of participants had analgesic support. The total MR treatment time ranged from 73 to 114 minutes. Mean error between desired and achieved targeting in a phantom was 2.9 $\pm$ 1.8 mm while 6.2 $\pm$ 1.9 mm was achieved in patient studies, assessed either with MRTI or MR-ARFI measurements. MRTI and MR-ARFI were successful in 60 $\%$ and 70 $\%$ of patients, respectively. Conclusion: The targeting accuracy allows the accurate placement of the focal spot using electronic steering capabilities of the transducer. The use of both volumetric MRTI and MR-ARFI provides complementary treatment planning and monitoring information during the treatment, allowing the treatment of all breast anatomies, including homogeneously fatty breasts.

Background Ductal carcinoma in situ (DCIS) represents 15% of all breast cancers in France. The first national survey was conducted in 2003. The present multi-center real-life practice survey aimed at assessing possible changes in demographic, clinical, pathologic, and treatment features. Material and Methods From March 2014 to September 2015, patients diagnosed with DCIS from 71 centers with complete information about age, diagnostic features, and treatment modalities were prospectively included. Results A total of 2125 patients with a median age of 58.6 years from 71 centers were studied. DCIS was diagnosed by mammography in 87.5% of cases. Preoperative biopsy was performed in 96% of cases. The median tumor size was 15 mm. Nuclear grade was low, intermediate, and high in 12%, 36%, and 47% of cases, respectively. Margins were considered to be negative in 83% of cases. Overall mastectomy and lumpectomy rates were 25% and 75%, respectively. The immediate breast reconstruction rate was 50%. Sentinel node biopsy and axillary dissection rates were 41% and 2.6%, respectively. After lumpectomy, 97% of patients underwent radiotherapy, and 32% received a boost dose. Only 1% of patients received endocrine therapy. Compared with our previous survey, the median tumor size remained the same, and the proportion of high-grade lesions increased by 9%. The mastectomy rate decreased by 4%. Conclusions The clinical practice identified in this survey complies with French DCIS guidelines. About 10% of patients with low-grade DCIS may be eligible to participate in treatment de-escalation trials.

The reverse sequence of neoadjuvant chemotherapy, preoperative radiotherapy, mastectomy then immediate breast reconstruction is currently proposed for selected patients with locally advanced breast cancer. Few studies have compared it to the standard sequence of neoadjuvant chemotherapy, mastectomy and radiotherapy with or without differed reconstruction. Our study compares overall (OS) and recurrence-free (RFS) survivals of breast cancer patients treated with reverse sequence compared to the standard technique.In this retrospective, single center study at a Comprehensive Cancer Center in France, patients were included if: female, agelt;65y, had received neoadjuvant chemotherapy, mastectomy and radiotherapy, and were M0. Outcomes for patients treated by reverse sequence (RS) are compared to those for patients treated by standard sequence (ST). Data was collected from medical records.From January 2009 to April 2018, 222 eligible patients were treated, 46 by RS and 176 by ST. Mean follow-up was 61.7 months. Five-year OS and RFS did not differ between groups. 5-yr OS: 88.4% 95%CI [74.1-95.0] for RS and 81.5% 95%CI [74.0-87.0] for ST (P = 0.4412); 5-yr RFS: 78.3% 95%CI [61.9-88.3] for RS and 70.1% 95%CI [62.2-76.7] for ST (P = 0.3003). Overall treatment time was significantly shorter in the RS group, and the rate of severe surgical complications did not differ between groups.For locally advanced breast cancer patients with an indication for radiation therapy the reverse sequence offers similar safety and efficacy results as the standard treatment while allowing immediate breast reconstruction. However, careful patient selection is necessary, particularly with regard to preoperative lymph node invasion.

The similarities between sporadic basal-like breast cancer (BLBC) and BRCA1-mutated breast tumours raise the possibility that deregulation of the same pathway may underlie these tumour types. The aim of this study was to determine if PTEN aberrations are characteristic of both BRCA1 tumours and sporadic TN breast carcinomas with low BRCA1 expression, and can thus be used to identify sporadic tumours potentially sensitive to PARP inhibitors. Twelve BRCA1 tumours, 19 non-BRCA familial breast tumours and 71 unselected TN breast carcinomas were screened for PTEN mutations and assessed for PTEN expression and BRCA1 mRNA expression. Loss of PTEN expression was observed in 67% of BRCA1 tumours and more specifically in 89% of TN BRCA1 tumours highlighting the link between PTEN loss and BLBC in the context of germline BRCA1 mutations. Regarding unselected TN tumours, 56% showed PTEN expression loss and 35% displayed low BRCA1 mRNA expression. Unlike familial breast cancers with low BRCA1 mRNA expression, no significant correlation was observed between the loss of PTEN expression and low BRCA1 mRNA expression in this unselected TN tumours panel. Our data suggest that, unlike the germinal context, PTEN and BRCA1 alterations in sporadic TN breast tumours are independent events.

Introduction Ductal carcinoma in situ (DCIS) accounts for 15% of all breast cancers and generally, the prognosis is good if treated optimally. The standard treatment includes breast conservative surgery along with adjuvant radiotherapy. Skin-sparing mastectomy (SSM) preserves the breast skin envelope but its oncological safety poses a few concerns. Moreover, no DCIS-specific studies have compared the local recurrence (LR) rate following total mastectomy (TM) or SSM. We evaluated the LR rate in DCIS patients who underwent either TM or SSM. Methods This is a retrospective study on women who underwent mastectomy with or without immediate breast reconstruction or secondary reconstruction for pure DCIS of the breast. All patients treated at Institut Bergonie by mastectomy for DCIS from January 1990 to December 2010 were included. LR and overall survival (OS) rates were estimated. Results The study population included 399 patients who were categorized into two groups, 207 in the TM group and 192 in the SSM group. At 10 years of follow-up, the LR rate was 0.97% in the TM group and 1.04% in the SSM group (p = NS). The OS of the entire population was 94.7% [95% CI; 91.6–96.7], 92.8% [95% CI, 87.9–95.8] for the TM group and 96.8% [95% CI, 91.6–98.8] for the SSM group. Conclusions In our study, the LR rate following mastectomy is low, regardless of the surgical technique used, with an excellent OS at 10 years.

Simple Summary After the results of many trials, it is now accepted to omit axillary dissection in selected patients with limited axillary involvement. However, the external validity of these trials is questionable. Our study aimed to evaluate the accuracy of the real French population representativity in the SERC (Sentinelle Envahi et Randomisation du Curage) trial population for patients with breast cancer (BC) associated with sentinel node (SN) micro-metastasis and the differences between the studied population and the real French population. The secondary aim was to compare the French and the Swedish populations of patients with SN micro-metastasis. The findings of our study in addition to the previously demonstrated concordance between the SENOMIC (Sentinelle node Micrometastasis) trial and the Swedish National Breast Cancer Registry (NKBC) populations implied that the results of both the SERC and the SENOMIC trials can be applied to both the French and Swedish real populations. Abstract Many trials confirmed the safety of omitting axillary dissection in the selected patients treated for early breast cancer. The external validity of these trials is questionable. Our study aimed to evaluate the accuracy of the French population representativity in the SERC trial and the differences between these two populations as well as comparing the French and the Swedish populations (the SENOMIC trial population and the Swedish National Breast Cancer Registry (NKBC) cohort) of patients with sentinel node (SN) micro-metastasis. A higher rate of smaller tumors and grade 1 tumors was observed in the French cohort when compared to the SERC population. Our findings conclude that both French populations show similar characteristics. Positive non-sentinel node (NSN) rates at completion axillary lymph node dissection (ALND) were 10.28 % and 11.3 % in the SERC trial and French cohort, respectively (p = 0.5). The rate of grade 1 tumors was lower in the SENOMIC trial (16.2%) and in the NKBC cohort (17.4%) compared to the SERC trial population (27.3%) and the French cohort (34.4%). Our findings in addition to the previously demonstrated concordance between the SENOMIC trial and the NKBC populations imply that the results of both the SERC and the SENOMIC trials can be applied to both French and Swedish real populations.

International audience; Background: Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting.- methods: Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model.Results: The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers.Conclusion: The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH.

Background Few data are available on survival and predictive factors in early breast cancer (BC) patients treated with neoadjuvant endocrine therapy (NET). Methods This is a pooled analysis of two multicentre, randomised non-comparative phase 2 clinical trials evaluating neoadjuvant anastrozole and fulvestrant efficacy for postmenopausal HR+/HER2- breast cancer patients: HORGEN (NCT00871858) and CARMINA02 (NCT00629616) studies. Results In total, 236 patients were included in CARMINA02 and HORGEN trials. Modified intention-to-treat analysis was available for 217 patients. Median follow-up was 65.2 months. Relapse-free survival (RFS) and overall survival (OS) at 5 years were 83.7% (95% CI: 77.9–88) and 92.7% (95% CI: 88.2–95.6), respectively, with no difference between treatment arms. On univariate analysis, tumour staging (T2 vs T3–4; p = 0.0001), Ki-67 at surgery (≤10% vs >10%; p = 0.0093), pathological tumour size (pT1–2 vs pT3–4; p = 0.0012) and node status (pN negative vs positive; p = 0.007), adjuvant chemotherapy (p = 0.0167) and PEPI score (PEPI group I + II vs III; p = 0.0004) were associated with RFS. No events were observed in patients with pathological response according to the Sataloff classification. Multivariate analysis showed that preoperative endocrine prognostic index (PEPI) group III was associated with significantly worse RFS (p = 0.0069, hazard ratio = 3.33 (95% CI: 1.39–7.98)). Conclusions Postmenopausal HR+/HER2- breast cancer patients receiving NET generally have a favourable outcome. The PEPI score identifies a subset of patients of poorer prognosis who are candidates for further additional treatment.

Introduction The aim of this study was to examine changes in therapeutic practices for early breast cancer T0-2 N0 managed by upfront surgery and SLNB. Population Between 1999 and 2012, 15.508 patients were treated. Four periods were determined: 1999–2003, 2004–2006, 2007–2009 and > 2009. Five tumor subtypes were defined according to hormonal receptors (HR) and Her2: Luminal A (HR + Her2- Grade 1–2), Her2 (Her2+ HR-), Triple-negative (HR- Her2-), Luminal B Her2- (HR + Her2- Grade 3), Luminal B Her2+ (HR + HER2+). Methods Rates of axillary lymph node dissection (ALND), adjuvant chemotherapy ± trastuzumab, endocrine treatment, mastectomy and post mastectomy radiotherapy (PMRT) were analyzed according to treatment periods with univariate and multivariate analysis. Overall and disease-free survivals were analyzed according to treatment periods adjusted for HR and then for tumor subtypes. Results Rates of ALND, adjuvant chemotherapy and endocrine treatment varied significantly according to treatment periods, for HR positive and negative tumors. ALND rate decreased for all tumor subtypes with a decrease of adjuvant chemotherapy rate for Luminal A tumors and an increase for Luminal B Her2+ and Her2-tumors. Endocrine treatment rate decreased for Luminal A and increased for Luminal B Her2+ tumors. In multivariate analysis, these modifications with time remained significant. Mastectomy and PMRT rates increased. In multivariate analysis, overall and disease-free survivals increased during successive periods. Conclusion A global therapeutic de-escalation in ALND and adjuvant systemic treatment, combined with an actual escalation in some specific subsets was demonstrated, but without negative impact on survival.

There is a need to refine the prognosis of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy (NAC) and to study the influence of the tumor microenvironment. We evaluated the prognostic value of pathological and immune markers in TNBC with residual disease (RD) after NAC. In a series of 186 TNBC patients treated by NAC, we assessed the prognostic value of the Residual Cancer Burden (RCB) index. In 109 patients with RD, we studied the impact of clinicopathological features and tumor immune response in the residual tumor on overall survival (OS) and distant recurrence-free interval (DRFI). In the whole group, the OS and DRFI, at 3 years, were statistically different between the different classes of RCB (P = 0.0004 and P

Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers.All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts.79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%).Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery.

International audience; BACKGROUND:Tumour features associated with isolated invasive breast cancer (BC) ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. Our objective was to investigate these points.METHODS:Patients were retrospectively identified from a cohort of patients who underwent BCT for invasive BC in 16 cancer centres. End-points were ILR rate and OS. The impact of ILR on OS was assessed by multivariate analysis (MVA) for all patients and according to endocrine receptors (ERs) and grade or tumour subtypes.RESULTS:Of 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR 1.42, p = 0.010; ERs+/Grade3: HR 1.41, p = 0.067; ERs-: HR 2.14, p

Resume Objectif Depuis les dernieres recommandations nationales elaborees par l’Institut national du cancer (INCa) et la Societe francaise de senologie et de pathologie mammaire (SFSPM) sur l’ensemble de la prise en charge diagnostique et therapeutique des carcinomes canalaires in situ (CCIS), de nouvelles publications ont fait emerger des interrogations en termes de bonnes pratiques et sur les possibilites de desescalade therapeutique dans la prise en charge des CCIS. L’actualisation de ces recommandations intervient dans un contexte de questionnement sur le surdiagnostic et son corollaire le surtraitement. Elle met a la disposition des professionnels des informations sur les bonnes pratiques correspondant a l’etat le plus recent des connaissances scientifiques et etudie notamment les possibilites de desescalade therapeutique. Methode Le processus d’elaboration est base sur une revue systematique de la litterature et sur le jugement argumente d’experts cliniciens au sein d’un groupe de travail multidisciplinaire. Avant publication, les recommandations sont revues par plus de cent experts cliniciens independants du groupe de travail. Resultats Cet article presente les recommandations nationales relatives a l’indication de l’IRM, la place de la macrobiopsie en cas de microcalcifications et la conduite a tenir en cas de CCIS de bas grade identifie par biopsie, dans le diagnostic des CCIS.

International audience; BACKGROUND:Invasive lobular carcinomas (ILCs) represent approximately 10% of all breast cancers. Despite this high frequency, benefit of adjuvant chemotherapy (CT) is still unclear.METHODS:Our objective was to investigate the impact of CT on survival in ILC. Patients were retrospectively identified from a cohort of 23,319 patients who underwent primary surgery in 15 French centers between 1990 and 2014. Only ILC, hormone-positive, human epidermal growth factor 2 (HER2)-negative patients who received adjuvant endocrine therapy (ET) were included. End-points were disease-free survival (DFS) and overall survival (OS). A propensity score for receiving CT, aiming to compensate for baseline characteristics, was used.RESULTS:Of a total of 2318 patients with ILC, 1485 patients (64%) received ET alone and 823 (36%) received ET + CT. We observed a beneficial effect of addition of CT to ET on DFS and OS in multivariate Cox model (HR = 0.61, 95% confidence interval, CI [0.41-0.90]; p = 0.01 and 0.52, 95% CI [0.31-0.87]; p = 0.01, respectively). This effect was even more pronounced when propensity score matching was used. Regarding subgroup analysis, low-risk patients without CT did not have significant differences in DFS or OS compared to low-risk patients with CT.CONCLUSION:ILC patients could derive significant DFS and OS benefits from CT, especially for high-risk patients.

International audience; BACKGROUND:The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment.METHODS:One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment.RESULTS:A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 53.8% (95% CI=39.5-67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 50.0% (95% CI=35.8-64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3-21.0) before, 3.2% (95% CI=1.9-5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1-22.5) before, 3.2% (95% CI=1.8-5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles.CONCLUSIONS:Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients.British Journal of Cancer advance online publication 14 July 2015; doi:10.1038/bjc.2015.247 www.bjcancer.com.

International audience; Background: Focusing on the current context of national and international recommendations, techniques development to evaluate and preserve fertility and patients’ claims, this study aims to make a survey about the management of patients’ breast cancer regarding oncofertility.Methods: Retrospective and analytic study of medical practices at Bergonié Institute of health professionals (medical oncologists, surgical oncologists, nurses) dedicated to the care of non-disseminated breast cancer patients younger than 37, needing medical treatment.Results: The number of participants was 230. The most interested practitioners in fertility theme are those of multidisciplinary consultation and surgeons (P < 0.001), with an increasing interest during last years (P < 0.05). The information about hypofertilizing risks of treatments are delivered most of the time by oncologists (57.7%). The motherhood project is expressed by 11 patients (4.9%) before treatment, only 4 of them receive information on the risks and 49 patients (21.7%) during follow-up. Only 24 patients (48% of the 49) are encouraged for motherhood.Conclusion: To satisfy patients’ requests, several improvements have to be made regarding the patients’ information, the health professionals’ awareness and care coordination.; Introduction: Dans le contexte actuel de revendications des patientes, développement des techniques de préservation de la fertilité, et recommandations (inter)nationales, notre étude a pour objectif de réaliser un état des lieux, concernant l’oncofertilité, chez des patientes en âge de procréer traitées pour cancer du sein.Méthodes: Étude rétrospective, unicentrique, analytique, des pratiques des intervenants de l’institut Bergonié (oncologues médicaux, chirurgiens, infirmières d’annonce), face aux patientes de moins de 37 ans, traitées pour un cancer du sein infiltrant non disséminé, nécessitant traitement médical.Résultats: Deux cents trente patientes ont été incluses, entre 2000 et 2010. Les praticiens s’intéressant le plus à la fertilité sont les chirurgiens et les comités multidisciplinaires (p < 0,001), avec une amélioration de l’intérêt des médecins ces dernières années (p < 0,05). L’information sur le caractère hypofertilisant des traitements est majoritairement donnée par l’oncologue médical (57,7 %). Un projet de maternité est exprimé par 11 patientes (4,9 %) en pré-thérapeutique dont 4 sont informées sur les risques des traitements, et par 49 patientes (21,7 %) durant le suivi. Seulement 24 patientes (48 % d’entre elles) y sont encouragées.Conclusion: Afin de répondre aux demandes des patientes, des améliorations sont à réaliser, dans l’information des patientes, la sensibilisation du personnel, et la coordination des soins.

Background While the addition of targeted therapy to neoadjuvant chemotherapy (NACT) dramatically increases the rate of pathological complete response in HER2-positive breast cancer, no reduction in the rate of mastectomy has been observed in randomised studies. Methods A retrospective single centre analysis of all patients treated with anti HER2-based NACT for T2–4 breast cancer, focusing on patients treated with mastectomy. Results Among 165 patients treated between June 2005 and July 2012, surgery was performed immediately post-NACT in 152 cases (92%). Breast-conserving surgery could be performed for 108 of the patients (71%), with a 4-year local relapse-free survival of 97%. A mastectomy was performed in two cases following patients’ wishes and in 37 cases based on pre-NACT findings (n = 18) or post-NACT outcomes (n = 19). For 21 out of the 37 cases, a good pathological response was observed, and multidisciplinary reanalysis suggests that breast-conserving surgery outright may have been sufficient for 12 patients. Finally, a salvage mastectomy based on post-lumpectomy pathological results was decided in five cases (11%). The 4-year metastasis-free survival was 84% for all patients operated on after NACT (n = 152). Conclusions Given the good efficacy of anti HER2-based NACT, breast-conserving surgery should be standard practice for most patients. Total mastectomy on the other hand should be restricted to a few patients, mainly those with positive margins on the lumpectomy specimen.

Background To examine outcomes of neoadjuvant endocrine therapy in daily practice to inform decision making. Methods We retrospectively selected 204 patients who received neoadjuvant endocrine therapy with T2 (≥30 mm) or T3 tumors, examining subsequent breast-sparing surgery and long-term outcomes. Results Neoadjuvant endocrine therapy was administered for 7.3 months (median) and breast-sparing surgery was achievable in 53% of patients. Smaller initial tumor size and modified version of the Scarff–Bloom and Richardson grades 1 to 2 were associated with breast-sparing surgery. Disease progression during treatment was 6.9%; actuarial risk of local relapse was 3% at 5 years and 15% at 10 years. Five- and 10-year metastasis relapse-free survival was 78% and 63%, respectively. Grade 3, negative progesterone receptors, and absence or slow response to neoadjuvant therapy were associated prognostic factors. Conclusion These daily practice data provide important information about feasibility, efficacy, and long-term results of neoadjuvant endocrine therapy and can be used to inform patients for decision making between mastectomy and endocrine induction therapy.

To define the prognostic value of isolated tumor cells (ITC), micrometastases (pN1mi) and macrometastases in early stage breast cancer (ESBC). We conducted a retrospective multicenter cohort study at 13 French sites. All the eligible patients who underwent SLNB from January 1999 to December 2008 were identified, and appropriate data were extracted from medical records and analyzed. Among 8001 patients, including 70% node-negative (n = 5588), 4% ITC (n = 305), 10% pN1mi (n = 794) and 16% macrometastases (n = 1314) with a median follow-up of 61.3 months, overall survival (OS) and recurrence-free survival (RFS) rates at 84 months were not statistically different in ITC or pN1mi compared to tumor-free nodes. Axillary recurrence (AR) was significantly more frequent in ITC (1.7%) and pN1mi (1.5%) compared to negative nodes (0.6%). Survival and AR rates of single macrometastases were not different from those of ITC or pN1mi. In case of 2 macrometastases or more, survival rates decreased and recurrence rates increased significantly. Micrometastases and ITC do not have a negative prognostic value. Single macrometastases might have an intermediate prognostic value while 2 macrometastases or more are associated with poorer prognosis.

PTEN plays a well-established role in the negative regulation of the PI3K pathway, which is frequently activated in several cancer types, including breast cancer. A nuclear function in the maintenance of chromosomal stability has been proposed for PTEN but is yet to be clearly defined. In order to improve understanding of the role of PTEN in mammary tumorigenesis in terms of a possible gene dosage effect, its PI3K pathway function and its association with p53, we undertook comprehensive analysis of PTEN status in 135 sporadic invasive ductal carcinomas. Four PTEN status groups were defined; complete loss (19/135, 14%), reduced copy number (19/135, 14%), normal (86/135, 64%) and complex (11/135, 8%). Whereas the PTEN complete loss status was significantly associated with estrogen receptor (ER) negativity (p=0.006) and in particular the basal-like phenotype (p

Background To estimate the proportion of elderly patients (>70 years) with breast cancer eligible for an Exclusive IntraOperative RadioTherapy (E-IORT) and to evaluate their local recurrence-free survival rate. Methods This retrospective study examining two cohorts focuses on patients over 70 years old: a multi-centric cohort of 1411 elderly patients and a mono-centric cohort of 592 elderly patients. All patients underwent conservative surgery followed by external radiotherapy for T0-T3 N0-N1 invasive breast cancer, between 1980 and 2008. Results Within each cohort two groups were identified according to the inclusion criteria of the RIOP trial (R group) and TARGIT E study (T group). Each group was divided into two sub-groups, patients eligible (E) or non-eligible (nE) for IORT. The population of patients that were eligible in the TARGIT E study but not in the RIOP trial were also studied in both cohorts. The proportion of patients eligible for IORT was calculated, according to the eligibility criteria of each study. A comparison of the 5-year local or locoregional recurrence-free survival rate between eligible vs non-eligible patients was made. In both cohorts, the proportion of patients eligible according to the RIOP trial’s eligibility criteria was 35.4 and 19.3%, and according to the TARGIT E study criteria was 60.9 and 45.3%. The 5-year locoregional recurrence-free survival rate was not significantly different between RE and RnE groups, TE and TnE groups. In both cohorts RE and (TE-RE) groups were not significantly different. Conclusions Our results encourage further necessary studies to define and to extend the eligibility criteria for per operative exclusive radiotherapy.

The objective of our study is to describe the practices of breast reconstruction in patients aged 70 years and over undergoing a radical mastectomy at institut Bergonié.We performed a detailed single-site retrospective study from January 2005 to December 2015. Through a computerized review, we have identified and analyzed all patients aged 70 years and over who underwent a breast reconstruction.Five hundred and ninety patients underwent a radical mastectomy during the period. Twenty-eight patients (4.7%) benefited from a breast reconstruction. Nineteen patients (67.9%) had an immediate breast reconstruction and 9 patients (32.1%) had a delayed breast reconstruction, within an average time of 2 years. Sixteen patients (57.1%) benefited from the insertion of an expander replaced by a permanent implant. Five patients (17.9%) benefited from the immediate placement of an implant. Six patients (21.4%) had a reconstruction by autologous latissimus dorsi flap and 1 patient (3.6%) by exclusive lipofilling. Four patients (14.3%) presented postoperative complications without the need for removal of an implant or flap loss. Twenty patients (71.4%) were satisfied with their final reconstruction.Breast reconstruction in elderly patients is possible. Further studies are needed to better describe French practices.

Since the last guidelines published by the French National Cancer Institute (INCa) and the learning society "Société française de sénologie et de pathologie mammaire (SFSPM)" in 2009 about diagnosis and management of ductal carcinoma in situ, new data raised issues about overdiagnosis and its consequences, overtreatment. Therefore, an update was necessary, to provide healthcare professionals up-to-date guidelines and study therapeutic desescalation in particular.The clinical practice guidelines development process is based on systematic literature review and critical appraisal by a multidisciplinary experts workgroup. The recommendations are thus based on the best available evidence and experts agreement. Prior to publication, the guidelines are also reviewed by more than 100 independent practitioners in cancer care delivery.This article presents French guidelines about MRI and vacuum assisted breast biopsy indications for DCIS diagnosis and the management of low-grade DCIS.

Controversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications.We conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected.5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients ≤35 years old. Triple negative and HER2 tumors were predominantly found in patients ≤35 (22.2% and 22.1%, p 0.01). A young age ≤40 years (p 0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60-2.63) or ≤35 years (p 0.001; [HR]: 3.86; 95% [CL]: 2.69-5.53) impacted on the indication of chemotherapy. Age ≤35 (p 0.001; [HR]: 2.01; 95% [CL]: 1.36-2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p 0.006; [HR]: 0.6; 95% [CL]: 0.40-0.86) and positive hormone receptor status (p 0.001; [HR]: 0.6; 95% [CL]: 0.54-0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients35-40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p 0.01).Young women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy.

To determine the efficacy and tolerance of ultrasonography (US)-guided percutaneous radiofrequency (RF) ablation with endocrine therapy in elderly patients with breast cancer who decline or are not candidates for surgery.Internal ethics committee approval was obtained, and patients gave informed written consent. Women older than 70 years with breast carcinoma, who had undergone neoadjuvant endocrine therapy within the past 6 months, underwent US-guided RF ablation while under local anesthesia and sedation. Only tumors measuring 3 cm or smaller and situated at least 1 cm from the skin, nipple, and chest wall were selected. Multitine electrodes were used. Endocrine therapy was continued for a total of 5 years, and breast irradiation was not performed. Clinical follow-up included US, mammography, and dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging every 2 months for 6 months and then every 6 months until 5 years. Primary end points were RF ablation efficacy at 1 year on the basis of DCE MR imaging follow-up and procedural tolerance. The secondary end point was delayed local efficacy at the end of endocrine therapy (5 years) on the basis of DCE MR imaging follow-up.Twenty-one women were treated from December 2004 to April 2010 (median age, 79 years; age range, 70-88 years). Efficacy was demonstrated at 1 year, with only one patient presenting with a local relapse. No general complications were noted. Skin burn occurred in four patients, with spontaneous healing after a maximum of 2 months. Ten patients were followed up for 5 years, with three additional patients presenting with cancer recurrence outside the ablation zone at 30, 48, and 60 months-including two with lobular carcinoma. Four patients died during the full follow-up, two of breast cancer-related causes and two of unrelated causes.RF ablation in elderly patients with nonresected breast cancer is well tolerated and efficient at 1-year follow-up. The technique is not recommended for lobular carcinoma.

International audience; PURPOSE: The risk of non sentinel node (NSN) involvement varies in function of the characteristics of sentinel nodes (SN) and primary tumor. Our aim was to determine and validate a statistical tool (a nomogram) able to predict the risk of NSN involvement in case of SN micro or sub-micrometastasis of breast cancer. We have compared this monogram with other models described in the literature. METHODS: We have collected data on 905 patients, then 484 other patients, to build and validate the nomogram and compare it with other published scores and nomograms. RESULTS: Multivariate analysis conducted on the data of the first cohort allowed us to define a nomogram based on 5 criteria: the method of SN detection (immunohistochemistry or by standard coloration with HES); the ratio of positive SN out of total removed SN; the pathologic size of the tumor; the histological type; and the presence (or not) of lympho-vascular invasion. The nomogram developed here is the only one dedicated to micrometastasis and developed on the basis of two large cohorts. The results of this statistical tool in the calculation of the risk of NSN involvement is similar to those of the MSKCC (the similarly more effective nomogram according to the literature), with a lower rate of false negatives. CONCLUSION: this nomogram is dedicated specifically to cases of SN involvement by metastasis lower or equal to 2 mm. It could be used in clinical practice in the way to omit ALND when the risk of NSN involvement is low.

Resume L’analyse extemporanee des ganglions sentinelles (GAS), preleves dans les carcinomes infiltrants du sein, permet, en cas d’envahissement metastatique, de realiser un curage axillaire dans le meme temps operatoire. Or, le principe, l’efficacite et la methode d’analyse extemporanee (cytologique, histologique) sont controverses. Le but de notre etude a ete d’evaluer la pertinence de l’examen extemporane cytologique pratique dans notre institut. Methodes Nous avons realise une analyse retrospective sur 24 mois des resultats de l’examen extemporane cytologique des GAS effectues pour des cancers mammaires invasifs cT1N0. Resultats Parmi les patientes, 187 femmes ont eu un examen de 360 GAS. Deux cent soixante-dix-sept GAS chez 156 femmes ont ete analyses extemporanement par cytologie. Dix-neuf sur 48 GAS positifs a l’analyse histologique definitive avaient ete detectes par l’examen extemporane cytologique (sensibilite 39,6 % ; specificite 100 %, valeur predictive positive [VPP] de 100 %, valeur predictive negative [VPN] de 88,7 %, exactitude 89,5 %). Le taux de faux negatif (FN) de l’examen extemporane cytologique est de 11,2 % par GAS et 18,3 % par patiente. Les facteurs predictifs de FN de l’extemporane cytologique, en analyse univariee, sont la presence d’emboles peritumoraux, de cT1b et c, de grade histologique SBR 2 ou 3. Seuls les emboles sont predictifs en analyse multivariee (OR = 3,3, IC 1,3-8,4). Conclusion La technique d’analyse extemporanee cytologique des GAS dans le cancer du sein presente un taux eleve de FN posant la question de la pertinence de cet examen dans ce cadre.

BACKGROUND: Lymphovascular invasion (LVI) is a widely recognized prognostic factor in lymph node-negative breast cancers. However, there are only limited and controversial data about its prognostic significance in lymph node-positive patients. METHODS: Among 931 patients operated on and monitored at the authors' institution for an invasive breast carcinoma between 1989 and 1992, all 374 lymph node-positive breast cancers entered the study (median follow-up, 126 months). RESULTS: LVI was present in 46% of tumors and was associated with age ≤40 years (P = .02), high histological grade (P = .01), and negative estrogen receptor status (P = .032), but not with tumor size, number of involved lymph nodes, or HER-2/neu status. LVI was an independent prognostic factor for distant metastases (P = .002). Furthermore, in HER-2/neu–negative/hormone receptor-positive (n = 287) tumors, the number of independent prognostic factors (LVI, age, histological grade, number of involved lymph nodes, and tumor size) was associated with a 5-years metastasis-free survival ranging from 100% if no factors (n = 25) to 89% ± 2% if 1 or 2 factors (n = 186) and 67% ± 6 if 3, 4, or 5 factors (n = 76) were present (P < .001). CONCLUSIONS: LVI is an independent prognostic factor in lymph node-positive breast cancer and merits further prospective investigations as a decision tool in the adjuvant chemotherapy setting. Cancer 2010. © 2010 American Cancer Society.

Du fait du depistage du cancer du sein generalise en France depuis 2004, les cancers du sein in situ representent 15 a 20 % des nouveaux cancers du sein. Ces recommandations elaborees par l’Institut national du cancer et la Societe francaise de senologie et pathologie mammaire definissent les meilleures strategies de prise enchargede ces lesions. La mammographie et l’echographie bilaterale sont les examens d’imagerie de reference. Les indications de l’IRM mammaire sont limitees. Letraitement de reference des cancers canalaires in situ, quand il est realisable, comporte une tumorectomie et une radiotherapie. Les marges saines doivent etre au minimum de 2 mm. Le curage ganglionnaire n’a pas d’indication, et la place du ganglion sentinelle est precisee. Pour les cancers lobulaires in situ, les recommandations s’appuient sur la classification LIN (OMS 2003). La surveillance recommandee des cancers du sein in situ traites comporte au minimum un examen clinique et une mammographie annuels completes le plus souvent d’une echographie.

Background and purpose Breast sarcoma (BS) is a rare tumour. While surgical resection is the primary treatment, the role of radiation therapy (RT) and chemotherapy remains unclear. This study aimed at defining prognostic factors and treatment strategies. Materials and methods Data from 103 patients treated between 1976 and 2002 were collected. The median age was 55 years (range: 13–86); the median histological tumour size was 4.45 cm (range: 0.8–22). There were 42 angiosarcomas. Surgery consisted of wide excision in 34 cases, and total mastectomy in 69 cases. A total dose of 50 Gy in 25 fractions was delivered in 50 patients. At the completion of treatment, 89 patients had no residual tumour. Results After a median follow-up of 64 months, 56 patients developed recurrent disease: 38 presented a local relapse and 37 developed distant metastases. The 5-year disease-free survival (DFS) and overall survival (OS) were 44% (95% confidence interval [CI], 39–49%) and 55% (95% CI, 50–60%), respectively. In multivariate analysis, favourable prognostic factors for better local control were: no residual tumour after treatment, no cellular pleomorphism, and histology other than angiosarcoma. For DFS, the five favourable prognostic factors were non-menopausal status, no residual tumour after treatment, non-angiosarcoma histology, absence of tumour necrosis, and grade 1–2 histology. Conclusion While angiosarcoma has the worst prognosis, the outcome of the other types of sarcomas may be worsened by residual tumour after loco-regional treatment and high grade histology, a classical prognostic factor of the other soft tissue sarcomas. During surgical procedure axillary dissection is not mandatory.

The rate of axillary recurrence (AR) after sentinel lymph node biopsy is usually low but few studies investigated its impact on survival. Our aim was to determine the rate and predictive factors of AR in a large cohort of breast cancer patients and its impact on survival.From 1999 to 2013, 14,095 patients who underwent surgery for clinically N0 previously untreated breast cancer and had sentinel lymph node biopsy were analysed. A simplified score predictive of AR was established.Median follow-up was 55.2 months. AR was observed in 0.51% of cases, with a median time to onset of 43.4 months. In multivariate analysis, the occurrence of AR was significantly correlated with grade 2 or 3 disease, absence of radiotherapy and tumour subtype (hormonal receptor [HR]- / human estrogen receptor [HER]+). AR rates were 1% for triple-negative tumours, 2.8% for HER2-positive tumours, 0.4% for luminal A tumours, 0.9% for HER2-negative luminal B tumours, and 0.5% for HER2-positive luminal B tumours. A simplified score predictive of the occurrence of AR was established. Patients could be divided into three different score groups (p0.0001). In multivariate analysis, overall survival was significantly lower in cases of AR (p0.0001), age50, lymphovascular invasion, grade 3 disease, sentinel node (SN) macrometastases, tumour size20 mm, absence of chemotherapy and triple-negative phenotype. Survival in patients with AR was significantly lower in case of early-onset (2 years) AR (p = 0.017).Isolated AR is more common in Her2-positive/HR-negative triple-negative tumours with a more severe prognosis in triple-negative and Her2-positive/HR-negative tumours, and represents an independent adverse factor justifying an indication for systemic treatment for AR treatment. However, the benefit of any systemic treatment remains to be proven.

To present our single-centre prospective experience on the use of cryoablation (CA) applied to treat primary breast cancer (BC) in a cohort of patients unsuitable for surgical treatment. Twenty-three consecutive post-menopausal female patients (median age 85 years; range 56–96) underwent percutaneous CA of unifocal, biopsy-proven BC, under ultrasound/computed tomography (US/CT) guidance. Clinical and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) follow-ups were systematically scheduled at 3, 12, 18 and 24 months. Local tumour control was assessed by comparing baseline and follow-up DCE-MRI. Twenty-three BC (median size 14 mm) were treated under local anaesthesia (78.3 %) or local anaesthesia and conscious sedation (21.7 %). Median number of cryo-probes applied per session was 2.0. A “dual-freezing” protocol was applied for the first ten patients and a more aggressive “triple-freezing” protocol for the remaining 13. Median follow-up was 14.6 months. Five patients recurred during follow-up and two were successfully re-treated with CA. Five patients presented immediate CA-related complications: four hematomas evolved uneventfully at 3-month follow-up and one skin burn resulted in skin inflammation and skin retraction at 3 and 12 months, respectively. Percutaneous CA is safe and well tolerated for non-resected elderly BC patients. Procedures can be proposed under local anaesthesia only. Given the insulation properties of the breast gland, aggressive CA protocols are required. Prospective studies are needed to better understand the potential role of CA in the local treatment of early BC.

Focusing on the current context of national and international recommendations, techniques development to evaluate and preserve fertility and patients' claims, this study aims to make a survey about the management of patients' breast cancer regarding oncofertility.Retrospective and analytic study of medical practices at Bergonié Institute of health professionals (medical oncologists, surgical oncologists, nurses) dedicated to the care of non-disseminated breast cancer patients younger than 37, needing medical treatment.The number of participants was 230. The most interested practitioners in fertility theme are those of multidisciplinary consultation and surgeons (P0.001), with an increasing interest during last years (P0.05). The information about hypofertilizing risks of treatments are delivered most of the time by oncologists (57.7%). The motherhood project is expressed by 11 patients (4.9%) before treatment, only 4 of them receive information on the risks and 49 patients (21.7%) during follow-up. Only 24 patients (48% of the 49) are encouraged for motherhood.To satisfy patients' requests, several improvements have to be made regarding the patients' information, the health professionals' awareness and care coordination.

Purpose Adjuvant radiotherapy (RT) after a local excision (LE) for ductal carcinoma in situ (DCIS) aims at reduction of the incidence of a local recurrence (LR). We analyzed the long-term risk on developing LR and its impact on survival after local treatment for DCIS. Patients and Methods Between 1986 and 1996, 1,010 women with complete LE of DCIS less than 5 cm were randomly assigned to no further treatment (LE group, n = 503) or RT (LE+RT group, n = 507). The median follow-up time was 15.8 years. Results Radiotherapy reduced the risk of any LR by 48% (hazard ratio [HR], 0.52; 95% CI, 0.40 to 0.68; P < .001). The 15-year LR-free rate was 69% in the LE group, which was increased to 82% in the LE+RT group. The 15-year invasive LR-free rate was 84% in the LE group and 90% in the LE+RT group (HR, 0.61; 95% CI, 0.42 to 0.87). The differences in LR in both arms did not lead to differences in breast cancer–specific survival (BCSS; HR, 1.07; 95% CI, 0.60 to 1.91) or overall survival (OS; HR, 1.02; 95% CI, 0.71 to 1.44). Patients with invasive LR had a significantly worse BCSS (HR, 17.66; 95% CI, 8.86 to 35.18) and OS (HR, 5.17; 95% CI, 3.09 to 8.66) compared with those who did not experience recurrence. A lower overall salvage mastectomy rate after LR was observed in the LE+RT group than in the LE group (13% v 19%, respectively). Conclusion At 15 years, almost one in three nonirradiated women developed an LR after LE for DCIS. RT reduced this risk by a factor of 2. Although women who developed an invasive recurrence had worse survival, the long-term prognosis was good and independent of the given treatment.

Background Despite entering complete remission after primary treatment, a substantial proportion of patients with early stage breast cancer will develop metastases. Prediction of such an outcome remains challenging despite the clinical use of several prognostic parameters. Several reports indicate that genomic instability, as reflected in specific chromosomal aneuploidies and variations in DNA content, influences clinical outcome but no precise definition of this parameter has yet been clearly established. Methods To explore the prognostic value of genomic alterations present in primary tumors, we performed a comparative genomic hybridization study on BAC arrays with a panel of breast carcinomas from 45 patients with metastatic relapse and 95 others, matched for age and axillary node involvement, without any recurrence after at least 11 years of follow-up. Array-CGH data was used to establish a two-parameter index representative of the global level of aneusomy by chromosomal arm, and of the number of breakpoints throughout the genome. Results Application of appropriate thresholds allowed us to distinguish three classes of tumors highly associated with metastatic relapse. This index used with the same thresholds on a published set of tumors confirms its prognostic significance with a hazard ratio of 3.24 [95CI: 1.76-5.96] p = 6.7x10-5 for the bad prognostic group with respect to the intermediate group. The high prognostic value of this genomic index is related to its ability to individualize a specific group of breast cancers, mainly luminal type and axillary node negative, showing very high genetic instability and poor outcome. Indirect transcriptomic validation was obtained on independent data sets. Conclusion Accurate evaluation of genetic instability in breast cancers by a genomic instability index (G2I) helps individualizing specific tumors with previously unexpected very poor prognosis.

PTEN plays a well-established role in the negative regulation of the PI3K pathway, which is frequently activated in several cancer types, including breast cancer. A nuclear function in the maintenance of chromosomal stability has been proposed for PTEN but is yet to be clearly defined. In order to improve understanding of the role of PTEN in mammary tumorigenesis in terms of a possible gene dosage effect, its PI3K pathway function and its association with p53, we undertook comprehensive analysis of PTEN status in 135 sporadic invasive ductal carcinomas. Four PTEN status groups were defined; complete loss (19/135, 14%), reduced copy number (19/135, 14%), normal (86/135, 64%) and complex (11/135, 8%). Whereas the PTEN complete loss status was significantly associated with estrogen receptor (ER) negativity (p=0.006) and in particular the basal-like phenotype (p0.0001), a reduced PTEN copy number was not associated with hormone receptor status or a particular breast cancer subtype. Overall, PI3K pathway alteration was suggested to be involved in 59% (79/134) of tumors as assessed by human epidermal growth factor receptor 2 overexpression, PIK3CA mutation or a complete loss of PTEN. A complex PTEN status was identified in a tumor subgroup which displayed a specific, complex DNA profile at the PTEN locus with a strikingly similar highly rearranged pan-genomic profile. All of these tumors had relapsed and were associated with a poorer prognosis in the context of node negative disease (p=1.4 × 10(-13) ) thus may represent a tumor subgroup with a common molecular alteration which could be targeted to improve clinical outcome.

Intraoperative examination of sentinel lymph nodes (SLN) in breast cancer can avoid a new surgical procedure in case of positive SLN, but its value, efficacy and the methods used are still controversial. The aim of our study was to evaluate the imprint cytology intraoperative method of SLN analysis performed at our institution. We did a retrospective study of the sentinel lymph node procedures performed during a period of 24 months on cT1N0 unifocal breast cancers. Intraoperative procedure was mainly by imprint cytology (touch prep). A SLN procedure was performed on 187 women with 360 SLN. Two hundred and seventy-seven SLN among 156 women were analyzed intraoperatively by touch prep. 19/48 positive SLN were detected by intraoperative touch prep (sensitivity 39.6%; specificity 100%; positive predictive value 100%; negative predictive value 88.7%, accuracy 89.5%). False negative rate of cytological intraoperative examination of SLN was 11,2% by SLN and 18,3% by patient. By univariate analysis, this rate significantly increased with lymphovascular invasion, tumor size cT1b and c and histological SBR grade 2 or 3. By multivariate analysis, only lymphovascular invasion was a predictive factor of intraoperative touch prep failure (OR = 3.3; IC 1.3-8.4). Intraoperative imprint cytology of SLN in breast cancer is associated with a high rate of false negativity that questions its use in this setting.

Background Great variability in breast cancer (BC) treatment practices according to patient, tumour or organisation of care characteristics has been reported but the relation between these factors is not well known. In two French regions, we measured compliance with Clinical Practice Guidelines for non-metastatic BC care management and identified factors associated with non-compliance at clinical and organisational levels. Methods Eligible patients had invasive unilateral BC without distant metastases and at least two contacts with one of the two regional healthcare systems (2003-2004) in the first year after diagnosis. Medical data were collected from patient medical records in all public and private hospitals (99 hospitals). The care process was defined by 20 criteria: clinical decisions for treatment and therapeutic procedures. Each criterion was classified according to level of compliance ("Compliant", "Justifiable" and "Not Compliant") and factors of non-compliance were identified (mixed effect logistic regression). Results 926 women were included. Non-compliance with clinical decisions for treatment was associated with older patient age (OR 2.1; 95%CI: 1.3-3.6) and region (OR 3.0; 95%CI: 1.2-7.4). Non-compliance with clinical decisions for radiotherapy was associated with lymph node involvement or the presence of peritumoural vascular invasion (OR 1.5; 95%CI: 1.01-2.3) and non-compliance with overall treatment (clinical decisions for treatment + therapeutic procedures) was associated with the presence of positive lymph nodes (OR 2.0; 95%CI: 1.2-3.3), grade III versus grade I (OR 2.9; 95%CI: 1.4-6.2), and one region of care versus another (OR 3.5; 95%CI: 1.7-7.1). Finally, heterogeneity of compliance in overall treatment sequence was identified between local cancer units (p < 0.05). Conclusion This study provides interesting insights into factors of non-compliance in non-metastatic BC management and could lead to quality care improvements.

Secondary tumours (ST) represent a major concern in survivors of Hodgkin's disease (HD). Breast cancer (BC) is the most frequent ST among young treated women.One hundred and eighty-nine women treated for HD by radiotherapy (RT) and/or chemotherapy (CT) subsequently developed 214 BCs.Median age at HD diagnosis was 25 years (34% were less than 20). Median interval between HD and BC was 18.6 years, with a 42-year median age at first BC. According to the TNM classification, there were 30 (14%) T0 (non palbable lesions), 86 (40%) T1, 56 (26%) T2, 13 (6%) T3T4 and 29 (14%) Tx. There were 25 (13.2%) contralateral BC. 160 (75%) and 15 (7%) tumours were infiltrating ductal and lobular carcinomas, 7 (3.3%) were other subtypes and 27 (22%) DCIS. The rate of axillary nodal involvement was 32%. Among 203 operated tumours, 79 (39%) were treated by breast conserving surgery (BCS), with RT in 56 (71%) cases. CT and hormonal treatment were delivered in 51% and 45% of the patients. With a 50-month median follow-up, local recurrence occurred in 12% of the tumours (9% after mastectomy, 21% after lumpectomy alone and 13.7% after lumpectomy with RT). Metastasis occurred in 47 (26%) patients. The risk factors were pN+, pT, high SBR grade and young age (50 years). The ten-year overall and specific survival rates were 53% and 63.5%, respectively. The ten-year specific survival rates were 79% for pT0T1T2, 48% for pT3T4 (p = 0.0002) and 79% for pN0 versus 38.5% for pN+ (p = 0.00026). Among 67 deaths, 43 (73%) were due to BC.Patients and physicians should be aware that BC is the most frequent secondary tumour in young women treated for HD. The new RT modalities (lower doses and involved fields) may decrease the risk in the future. However, these women require a careful monitoring as from 8 to 10 years after HD treatment, combining mammography, ultrasound and MRI according to several ongoing studies. BC with whole breast irradiation is feasible in some selected cases.