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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.

Background and Objectives The French Sentimag feasibility trial evaluated a new method for the localization of breast cancer sentinel lymph node (SLN) using Sienna+®, superparamagnetic iron oxide particles, and Sentimag® detection in comparison to the standard technique (isotopes ± blue dye). Methods We conducted a prospective multicentric paired comparison trial on 115 patients. SLN localization was performed using both the magnetic technique and the standard method. Detection rate and concordance between magnetic and standard tracers were calculated. Post-operative complications were assessed after 30 days. Results Results are based on 108 patients. SLN identification rate was 98.1% [93.5–99.8] for both methods, 97.2% [92.1–99.4] for Sienna+® and 95.4% [89.5–98.5] for standard technique. A mean of 2.1 SLNs per patient was removed. The concordance rate was 99.0% [94.7–100.0%] per patient and 97.4% [94.1–99.2] per node. Forty-six patients (43.4%) had nodal involvement. Among involved SLNs, concordance rate was 97.7% [88.0–99.9] per patient and 98.1% [90.1–100.0] per node. Conclusions This new magnetic tracer is a feasible method and a promising alternative to the isotope. It could offer benefits for ambulatory surgery or sites without nuclear medicine departments. J. Surg. Oncol. 2016;9999:XX–XX. © 2016 Wiley Periodicals, Inc.

Benefit of adjuvant trastuzumab-based chemotherapy for node-positive and/or1 cm human epidermal growth factor receptor 2-positive (HER2+) breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidence that adjuvant chemotherapy with or without trastuzumab is effective in pT1abN0 HER2+ tumors is still limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy ± trastuzumab on outcome in this subpopulation.A total of 356 cases of pT1abN0M0 HER2 + breast cancers were retrospectively identified from a large cohort of 22,334 patients, including 1248 HER2+ patients who underwent primary surgery at 17 French centers, between December 1994 and January 2014. The primary end point was disease-free survival (DFS). A multivariate Cox model was built, including adjuvant chemotherapy, tumor size, hormone receptor status, and Scarff Bloom Richardson (SBR) grade.A total of 138 cases (39%) were treated with trastuzumab-based chemotherapy, 29 (8%) with chemotherapy alone, and 189 (53%) received neither trastuzumab nor chemotherapy. Adjuvant chemotherapy ± trastuzumab was associated with a significant DFS benefit (3-year 99 vs. 90%, and 5-year 96 vs. 84%, Hazard ratio, HR 0.26 [0.10-0.67]; p = 0.003, logrank test) which was maintained in multivariate analysis (HR 0.19 [0.07-0.52]; p = 0.001). Metastasis-free survival was also increased (HR 0.25 [0.07-0.86]; p = 0.018, logrank test) at 3-year (99 vs. 95%) and 5-year (98 vs. 89%) censoring. Exploratory subgroup analysis found DFS benefit to be significant in hormone receptor-negative, hormone receptor-positive, and pT1b tumors, but not in pT1a tumors.Adjuvant chemotherapy ± trastuzumab is associated with a significantly reduced risk of recurrence in subcentimeter node-negative HER2+ breast cancers. Most of the benefit may be driven by pT1b tumors.

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.

L’Institut national du cancer (INCa) et la Societe francaise de senologie et de pathologie mammaire (SFSPM), avec l’appui d’un groupe de travail pluridisciplinaire, diffusent les recommandations nationales sur une selection de 11 questions actuellement debattues dans la prise en charge du cancer du sein infiltrant non metastatique. Ces recommandations ont ete etablies apres une recherche exhaustive et analyse critique des donnees recentes de la litterature. Elles ont ete revues par 100 relecteurs independants du groupe de travail. Trois des questions d’actualite concernaient le bilan initial: place de l’echographie axillaire, indications et modalites du bilan d’extension et place de l’IRM cerebrale chez des patientes atteintes de tumeurs surexprimant HER2. Cinq des questions d’actualite concernaient la radiotherapie: indications du complement de dose apres irradiation de la glande mammaire, de l’irradiation hypofractionnee, de l’irradiation partielle, de l’irradiation de la chaine mammaire interne, et enfin indications de la radiotherapie apres chimiotherapie neoadjuvante. Trois questions concernaient les traitements systemiques: indication du trastuzumab chez des patientes atteintes de tumeurs infracentimetriques et surexprimant HER2, place d’Adjuvant ! Online et du Nottingham Pronostic Index, les delais optimaux entre la chirurgie et la chimiotherapie.

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.

Purpose In daily clinical practice, the indication for adjuvant chemotherapy (CT) is relatively easy to make in patients with early hormone-receptor-positive (HR+) breast cancer with either very poor or very good clinicopathological prognostic variables. However, this decision is much more difficult in patients with intermediate clinicopathological prognostic variables. Here, we evaluate the value of a gene-expression profile identified by the Prosigna gene signature assay in guiding treatment decision-making in patients with these intermediate features. Methods A consecutive cohort of 577 HR + breast cancer patients surgically treated in a single institution between January 2012 and December 2012 was evaluated. From this population, pre- and post-menopausal patients with intermediate prognosis clinicopathological variables were identified and indication of adjuvant CT in these patients was recorded. The gene signature assay was performed retrospectively in this intermediate risk group. Descriptive statistics are presented. Results Among 96 intermediate-risk patients, 64 postmenopausal patients underwent gene signature testing. Subtype distribution was as follows: Luminal A (N = 33; 51.6%), Luminal B (N = 31; 48.4%). Risk of recurrence (ROR) distribution was as follows: ROR-low (n = 16; 25%); ROR-intermediate (N = 26; 40.6%); and ROR-high (N = 22; 34.4%). CT was subsequently administered in 18.7%, 53.8% and 59.0% of the ROR-low, ROR-intermediate and ROR-high groups, respectively. With the use of the gene signature assay, 59.4% of the intermediate cases were re-classified to either ROR-low or ROR-high risk categories. In the ROR-intermediate group, 11/26 patients (42.3%) had Luminal A and 15/26 (57.7%) had Luminal B. Due to follow-up time constraints, no patient outcome results were evaluated. Conclusion The gene signature assay provides clinically useful information and improved treatment decision-making in patients with intermediate risk based on clinicopathological factors. Determining the patient's intrinsic subtype and ROR can aid clinicians in deciding whether CT should be indicated.

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.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 40 - N° 4 - p. 297-304

The aim of this study was to compare the complete pathologic response (CPR) rate in 56 nonmetastatic inflammatory breast cancer patients according to the classification used and to look for a correlation between the CPR and overall survival. Initial biopsies and mastectomy specimens were reviewed by the same pathologist. The clinical response rate was 75%. A CPR was observed in 11 cases according to Sataloff, three according to Chevallier and five according to the NSABP. There was no correlation between the clinical and pathologic responses and none of them was predictive of relapse free survival or overall survival. We propose a standardization of the pathologic process of the mastectomy specimens so that a CPR has a clear definition across the institutions, with a good reproducibility whatever the classification used.

Resume La technique RT-PCR en temps reel, GeneSearch™ Breast Lymph Node Assay (BLN), utilisant le mRNA de la mammaglobine et de la cytokeratine (CK) 19, permet de detecter en peroperatoire dans les ganglions sentinelles (GS) les metastases superieures a 0,2 mm. Materiel–methodes Quatre-vingt-trois patientes, 33 du centre Jean-Perrin et 50 du centre Oscar-Lambret, etaient eligibles pour cette etude, entre novembre 2007 et juin 2008. Chaque GS etait etudie pour moitie par BLN et pour moitie de facon habituelle (extemporane par empreintes +/- coupes congelees, inclusion en paraffine, coupes semi-seriees et etude immunohistochimique). Resultats Cent cinquante-sept GS etaient examines avec BLN, avec un nombre moyen et median de deux GS par pte. Quatorze patientes avaient des macro- ou des micrometastases ; le diagnostic a ete pose sept fois en extemporane, et le curage axillaire a pu etre alors immediat ; dans les sept autres cas, le diagnostic a ete fait par la methode BLN et/ou l’histologie definitive ; deux cas de discordance entre BLN et l’histologie definitive ont ete observes probablement en rapport avec l’echantillonnage. Sept curages ont ete realises secondairement, dont six auraient ete faits immediatement avec la methode BLN. La sensibilite de BLN est de 92 %, la specificite de 98 %, la valeur predictive negative de 98 % et la valeur predictive positive de 92 %. La duree moyenne de la procedure est de 40 minutes pour deux GS. Cette methode ne detecte pas les cellules tumorales isolees (CTI) pour lesquelles aucun consensus n’existe sur la realisation ou non d’un curage complementaire. Conclusion Dans cette etude, cette methode sensible et rapide permet d’augmenter le confort des patientes en reduisant le nombre de reinterventions pour curage.

PurposeTo determine the detection rate, the false-negative rate, and the accuracy of sentinel lymph node (SLN) detection after neoadjuvant chemotherapy (NAC) for advanced breast cancer.Patients and MethodsA prospective multicentric study was initiated to evaluate the results of SLN biopsy with the combined method after NAC for advanced large operable breast cancer.ResultsFrom September 2003 to March 2007, 195 patients enrolled from 12 institutions were found suitable for evaluation. The detection rate was 90% (176 of 195 patients), and the false-negative rate was 11.5% (six of 52 patients). Patients without axillary palpable nodes (N0) before NAC had a better detection rate compared with patients with axillary suspicious nodes (N1, 94.6% v 81.5%; P = .008). The false-negative rate was not correlated with clinical nodal status before NAC (9.4% v 15%; P = .66).ConclusionThis study confirms the feasibility of SLN biopsy after NAC in the case of large operable breast cancer. The detection rate, false-negative rate, and accuracy do not differ from those obtained in the case of early breast cancer without NAC, thus demonstrating the feasibility of SLN biopsy after NAC.

Axillary lymph node dissection in patients with ductal carcinoma in situ (DCIS) of the breast is not warranted because DCIS has no metastatic potential. However, the risk of microinvasive carcinoma (MIC) exists in large DCIS treated by mastectomy. The aim of this series is to evaluate the incidence of lymph node metastases in DCIS and DCIS-MIC. We analyzed retrospectively patients treated in six French cancer centers for pure DCIS or DCIS-MIC. Surgical procedures were lumpectomy or mastectomy associated with an axillary sentinel node (SN) procedure. We included 161 patients suffering from pure DCIS (116/161, 72%) or DCIS-MIC (45/161, 28%). Mean age was 56 years (32-78). We observed underestimation between core biopsy and histological result in 43/142 cases (30%). These data show an association between lesion size, solid subtype, high-grade DCIS, and underestimation. Forty-eight breast conservative procedures were performed and 113 mastectomies (70%). SN procedure was performed using blue dye, technetium, or both. In our series, we selected patients with a high risk of occult invasive carcinoma: high grade (55%), mean size (27 mm), and mastectomy (112). Six SN were found positive (3.7%). In the five patients treated with complete axillary dissection, the SN was the only positive node. SN in DCIS is an interesting procedure but not necessary for all patients. We need to focus on the subgroup with or a high risk of occult MIC: extensive calcifications or palpable mass, DCIS diagnosed by core biopsy and underestimation, multifocality, high grade, large tumor size, MIC, and mastectomy.

The French Sentimag feasibility trial evaluated a new method for the localization of breast cancer sentinel lymph node (SLN) using Sienna+®, superparamagnetic iron oxide particles, and Sentimag® detection in comparison to the standard technique (isotopes ± blue dye).We conducted a prospective multicentric paired comparison trial on 115 patients. SLN localization was performed using both the magnetic technique and the standard method. Detection rate and concordance between magnetic and standard tracers were calculated. Post-operative complications were assessed after 30 days.Results are based on 108 patients. SLN identification rate was 98.1% [93.5-99.8] for both methods, 97.2% [92.1-99.4] for Sienna+® and 95.4% [89.5-98.5] for standard technique. A mean of 2.1 SLNs per patient was removed. The concordance rate was 99.0% [94.7-100.0%] per patient and 97.4% [94.1-99.2] per node. Forty-six patients (43.4%) had nodal involvement. Among involved SLNs, concordance rate was 97.7% [88.0-99.9] per patient and 98.1% [90.1-100.0] per node.This new magnetic tracer is a feasible method and a promising alternative to the isotope. It could offer benefits for ambulatory surgery or sites without nuclear medicine departments. J. Surg. Oncol. 2016;113:501-507. © 2016 Wiley Periodicals, Inc.

Purpose: Leptin and obesity are clearly related, and obesity is associated with an increased risk of breast cancer. We therefore measured the expression of leptin and its two main receptor isoforms, OBR-L and OBR-S, in 322 breast cancers. We analyzed their relations with the classical prognostic factors and with survival to establish their links with breast cancer. Experimental Design: The expression of leptin and its receptors was quantified by real-time reverse transcription-PCR, using TaqMan fluorogenic probes and an ABI PRISM 7700 sequence detector system (Applied Biosystems, Courtaboeuf, France). TATA box binding protein was used to normalize expression. The human breast cancer cell, SK-BR-3, expressing the three targets, was chosen as the calibrator sample (i.e., target expression = 1). Results: All the tumors expressed both receptors, and 318 of 322 expressed leptin. These three variables correlated positively with each other and with estradiol and progesterone receptors, whereas they correlated negatively with histoprognostic grading and tumor diameter. OBR-L/OBR-S expression was inversely correlated with progesterone receptors. Patients with elevated OBR-S expression had longer relapse-free survival (P = 0.008), whereas high OBR-L/OBR-S was associated with a shorter relapse-free survival (P = 0.05). In Cox multivariate analyses, OBR-S maintained its prognostic value (P = 0.02; relative risk, 0.51). Conclusions: This study shows that (a) almost all of the breast cancers coexpress leptin and its two main isoforms of receptors, suggesting that the human epithelial breast cancer cells respond to leptin acting via an autocrine pathway; (b) high expression levels of leptin and leptin receptors are biological markers of a more differentiated phenotype; and that (c) OBR-S is an independent prognostic factor.

Summary Background An effective and well tolerated treatment is needed for patients with early HER2-positive breast cancer who do not achieve a pathological complete response after neoadjuvant therapy. The AVATAXHER trial aimed to predict pathological complete response early with the use of PET and to investigate whether the addition of bevacizumab could improve the proportion of patients achieving a pathological complete response in patients unlikely to respond to treatment. Methods AVATAXHER was a randomised, open-label, non-comparative, multicentre phase 2 study that enrolled women (≥18 years of age) with early-stage HER2-positive breast cancer from 26 oncology centres in France. Patients initially received two cycles of neoadjuvant docetaxel (100 mg/m 2 intravenously every 3 weeks) plus trastuzumab (8 mg/kg intravenously every 3 weeks then 6 mg/kg intravenously every 3 weeks for the second course). Before the first and second cycles, [ 18 F]-fluorodeoxyglucose (FDG) PET was done and the change in standardised uptake value was used to predict pathological complete response in each patient. Patients who were predicted to be responders on PET continued to receive standard therapy. Predicted non-responders were randomly assigned (2:1) to receive four cycles of docetaxel (100 mg/m 2 intravenously every 3 weeks) and trastuzumab (6 mg/kg intravenously every 3 weeks) plus bevacizumab (15 mg/kg intravenously every 3 weeks; group A) or continue on docetaxel plus trastuzumab alone (group B). Randomisation was open label and was done by an adaptive minimisation method. Although investigators and patients were aware of group assignment, the anatomo-pathologist in charge of centralised review of surgical samples and lymph nodes was masked to treatment assignment. The primary endpoint was centrally assessed pathological complete response according to the Chevallier classification. Efficacy analyses were done in the intention-to-treat population. Safety analyses in this Article were done on all patients who received at least one dose of treatment starting from cycle 3. Survival outcomes are not yet mature. This study is registered with ClinicalTrials.gov (NCT01142778) and EUDRACT (2009-013410-26). Findings Between May 19, 2010, and Oct 1, 2012, 152 patients were recruited for the study. Ten patients were subsequently excluded, leaving 142 patients in the intention-to-treat population. Of these 142 patients, 69 were predicted by [ 18 F]-FDG PET to be treatment responders after two cycles of treatment. The 73 predicted non-responders were randomly assigned to group A (n=48) and group B (n=25). Pathological complete responses were noted in 37 (53·6%, 95% CI 41·2–65·7) of the PET responders, 21 (43·8%, 29·5–58·8) of those in group A, and six (24·0%, 9·4–45·1) of those in group B. Incidences of grade 3–4 adverse events were similar in all three groups. The most common grade 3–4 adverse events were neutropenia (four in PET responders, five in group A, and three in group B), febrile neutropenia (one, three, and one, respectively), and myalgia (four, none, and one, respectively). Overall, 24 serious adverse events were reported in 15 patients (PET responders: nine events in four [6%] of 67 patients; group A: 14 events in ten [21%] of 47 patients; group B: one event in one [4%] of 25 patients). No deaths occurred during the study. Interpretation In patients with HER2-positive breast cancer, early PET assessment can help to identify non-responders to neoadjuvant docetaxel plus trastuzumab therapy. In these patients, the addition of bevacizumab can increase the proportion of patients achieving a pathological complete response. This potential new role for PET and the activity of bevacizumab in this setting need to be confirmed in larger phase 3 trials. Funding Roche France.

The current retrospective study was intended to obtain up-to-date and comprehensive data on surgical practice for breast cancer throughout France, including neoadjuvant chemotherapy (NAC) and the more recent surgical techniques of oncoplastic surgery (OPS). In June 2011, e-mail surveys were sent to 33 nationally renowned breast cancer surgeons from French public or private hospitals. The questionnaire focused on all the new cases of breast cancer treated in 2010. It included questions regarding surgical practices, with special emphases on NAC and OPS and other surgical characteristics. The overall response rate for the survey was 72.7 %. The total number of breast cancer cases from the survey was 13,762, which constitutes 26.2 % of the total incidence in 2010. Breast-conserving surgery (BCS) was performed for 71.0 % of the patients, and the results were similar throughout the types of practices. Of these patients, 13.9 % received OPS, either upfront or after NAC. Mastectomy was performed for 29.0 % of the patients, which is consistent with French official numbers. Among all patients, 16.3 % underwent surgery after NAC. To the authors’ knowledge, there are no publications of national figures on NAC or OPS rates to date. They are convinced that this study offers real-life surgical care information on a large population and covers France’s breast cancer surgical landscape. Mastectomy rates in France remain stable and consistent with those in other European countries. However, additional large-scale retrospective studies are required to confirm these figures and further explore NAC and OPS rates as well as surgical practice characteristics.

Resume Objectif Cette etude analyse les resultats de la « pratique clinique courante » chez 882 patientes traitees pour un carcinome canalaire in situ (CCIS) pur du sein dans 9 centres de lutte contre le cancer francais entre 1985 et 1995. Methode L’âge median etait de 53 ans ; 177 patientes (20 %) ont eu une mastectomie (M), 190 (22 %) une chirurgie conservatrice seule (CS) et 515 (58 %) une CS avec radiotherapie (CS + RT). Resultats Avec un recul median de 7 ans, les taux de recidive locale (RL) etaient de 2 %, 31 % et 13 % dans les groupes M, CS et CS + RT (p 60 ans (non significatif). Dans le groupe CS + RT, ces taux passent a 33 %, 13 % et 8 % (p Conclusion La mastectomie reste le traitement le plus sur des CCIS, assurant un controle local a 7 ans de 98 %. Dans notre etude, apres CS, la RT diminue tres significativement les taux de RL, avec des chiffres comparables a ceux des essais randomises NSABP B-17 et EORTC 10853. Le benefice de la RT est trouve dans tous les sous-groupes, quels que soient les facteurs cliniques ou histologiques consideres, mais son importance est variable. L’âge inferieur a 40 ans et l’exerese incomplete restent les deux facteurs majeurs de RL.

Resume Objectif Cette etude analyse les resultats de la « pratique clinique courante » chez 882 patientes traitees pour un carcinome canalaire in situ (CCIS) pur du sein dans 9 centres de lutte contre le cancer francais entre 1985 et 1995. Methode L’âge median etait de 53 ans ; 177 patientes (20 %) ont eu une mastectomie (M), 190 (22 %) une chirurgie conservatrice seule (CS) et 515 (58 %) une CS avec radiotherapie (CS + RT). Resultats Avec un recul median de 7 ans, les taux de recidive locale (RL) etaient de 2 %, 31 % et 13 % dans les groupes M, CS et CS + RT (p 60 ans (non significatif). Dans le groupe CS + RT, ces taux passent a 33 %, 13 % et 8 % (p Conclusion La mastectomie reste le traitement le plus sur des CCIS, assurant un controle local a 7 ans de 98 %. Dans notre etude, apres CS, la RT diminue tres significativement les taux de RL, avec des chiffres comparables a ceux des essais randomises NSABP B-17 et EORTC 10853. Le benefice de la RT est trouve dans tous les sous-groupes, quels que soient les facteurs cliniques ou histologiques consideres, mais son importance est variable. L’âge inferieur a 40 ans et l’exerese incomplete restent les deux facteurs majeurs de RL.

590Background: Benefit of adjuvant Trastuzumab-based chemotherapy for node-positive and/or > 1 cm HER2+ breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidences...

On March 30, 2010, Afssaps issued a health alert concerning breast implants brand PIP, after identifying a rupture rate higher than for other manufacturers. This alert asking the recall of all concerned patients with, according to the clinical examination, ultrasound and the desire of the patient, the possibility of explantation. We focus on PIP implanted in Oscar-Lambret center in Lille.A retrospective study on all patients carrying breast prosthesis PIP implanted in the Oscar-Lambret center. We are interested in the rate of patients who chose clinical and ultrasound monotoring, explantation rates, and prosthetic rupture.Thirty-three PIP (in 31 patients) have been implanted in the center between May 2, 2006 and March 9, 2010. The mean age of implants was 15.35 months. We realized eight explants, and found three intracapsular rupture. Two of three rupture were symptomatic.The majority of patients chose surveillance. Our short series does not give precise information about their risk of prosthetic failure, a national register should be established. The literature illustrates the low sensitivity of ultrasonography in the diagnosis of intracapsular rupture and the superiority of MRI. In the context of a health alert, could we propose a monitoring tool implant breast MRI in order to minimize the rate of patients carrying a ruptured implant (false negative).

L’examen extemporane du ganglion sentinelle (GS) en technique conventionnelle a une sensibilite mediocre [1], necessitant en cas de faux negatif revele par l’examen definitif une reprise secondaire en curage axillaire. La biologie moleculaire OSNA (One Step Nucleic Acid Amplification) permet d’ameliorer les performances de l’extemporane en recherchant par amplification l’ARN de la cytokeratine 19 [2]–[4].

Purpose The MammoSite is a device that was developed with the goal of making breast-conserving surgery (BCT) more widely available. Our objective was to evaluate the MammoSite device performances after an open cavity placement procedure and quality of life in highly selected patients with early-stage breast cancer. Methods and materials From March 2003 to March 2005, 43 patients with T1 breast cancer were enrolled in a phase II study. The median age was 72 years. Twenty-five (58%) patients were treated with high-dose rate brachytherapy using the MammoSite applicator to deliver 34Gy in 10 fractions. The main disqualifying factor was pathologic sentinel node involvement (10/43; 23%). There were no device malfunctions, migration or rupture of the balloon. Results After a median follow-up of 13 months, there were no local recurrences and one contralateral lobular carcinoma. Seventeen (68%), 13 (52%), 8 (32%), 5 (20%) and 2 (8%) patients had erythema, seroma, inflammation, hematoma and sever infection, respectively. Only 2 patients developed telangiectasia. At 1 year the rate of "good to excellent" cosmetic results was 84%. Significant changes in QoL were observed for emotional and social well-being between 3 and 12 months. At 24 months, only emotional well-being subscore changes were statistically significant ( p =0.015). Conclusions Our data in patients older than 60 years support the previously published data. Histologic features were the main disqualifying criteria. With higher skin spacing levels we observed very low incidence of telangiectasia. QoL evaluation indicates that baseline scores were satisfactory. Changes concerned emotional and social well-being.

To assess how surgeons in the Region Nord-Pas-de-Calais are incorporating sentinel lymph node biopsy (SLNB) into practice, before publication of official guidelines for this procedure.Five hundred thirty five general or gynecologic surgeons were mailed a questionnaire, with 81 performed breast cancer operations responding.Forty five surgeons (55%) performed fewer than 20 breast cancer operations per year (group A), 19 (23%) between 20 and 50 cancers (group B), 17 (21%) more than 50 breast cancers per year (group C). Forty nine (60%) performed SLNB: 38% in group A, 79% in group B, 100% in group C. Fifty seven p. cent used a combination of blue dye and sulfure colloide radioisotope, 22% use only radioisotope, 20% only blue dye. Eighty eight p. cent performed a learning curve, but with fewer than 20 procedures for 37%. Surgical training included scientific publications lecture (61%), formal training course (53%), or practical stage (41%).Surgeon with a high exposure to breast disease seemed to be most involved in the development of SLNB.

The " Standards, Options and Recommendations " (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the 20 French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. Objectives : To update the Standards, Options and Recommendations clinical practice guidelines for the management of ductal carcinoma in situ of the breast (DCIS). Methods : The working group identified the questions requiring up-dating from the previous guideline. Medline(r) and Embase(r) were searched using specific search strategies from year 1996 to year 2003. In addition several Internet sites were searched in October 2002. Results : Clinical guidelines have been defined for the management of diagnosis, treatment, follow-up, and treatment of recurrence of DCIS. The issue of hormone replacement therapy has also been addressed in the context of DCIS.

Between February 2001 and March 2003, 542 sentinel lymph node procedures were performed for localised breast carcinoma (T0-T1, N0, M0) without any previous treatment. Frozen sections were performed in 515 cases and they did not reveal metastases in 446 cases. Fifty-two micrometastases2 mm and 18 macrometastases were reported by definitive histopathological exam. Axillary clearance was performed in 50/70 patients (38 with micrometastases and 12 for macrometastases). Modalities of histopathological procedure are discussed and particularly number and interval of serial slides with or without immunochemistry ; 81.8% (36/44) of micrometastases were detected on the two first serial sections. Decisional value of axillary clearance performed in case of micrometastases is also evaluated.

Use of antibiotic prophylaxis (AP) in clean breast cancer surgery is still controversial. We assessed the efficacy of preoperative AP in a prospective study of 171 clean breast cancer procedures following previous anticancer chemotherapy. From June 1998 to July 2001, we analyzed 171 procedures. In 133 cases. AB with cefuroxime was performed. Wound infection rate was 3 out of 171 procedures (WI rate of 2/131 with AP compared with 1/37 without AP, p = 1.0). This study suggests that AP is not systematically required in breast cancer surgery following previous anticancer chemotherapy.

To assess the long-term outcome for women with ductal carcinoma in situ of the breast treated in current clinical practice by conservative surgery with or without definitive breast irradiation.We analyzed 705 cases of ductal carcinoma in situ treated between 1985 and 1995 in nine French regional cancer centers; 515 underwent conservative surgery and radiotherapy (CS+RT) and 190 CS alone. The median follow-up was 7 years.The 7-year crude local recurrence (LR) rate was 12.6% (95% confidence interval [CI] 9.4-15.8) and 32.4% (95% CI 25-39.7) for the CS+RT and CS groups, respectively (p0.0001). The respective 10-year results were 18.2% (95% CI 13.3-23) and 43.8% (95% CI 30-57.7). A total of 125 LRs occurred, 66 and 59 in the CS+RT and CS groups, respectively. Invasive or microinvasive LRs occurred in 60.6% and 52% of the cases in the same respective groups. The median time to LR development was 55 and 41 months. Nine (1.7%) and 6 (3.1%) nodal recurrences occurred in the CS+RT and CS groups, respectively. Distant metastases occurred in 1.4% and 3% of the respective groups. Patient age and excision quality (final margin status) were both significantly associated with LR risk in the CS+RT group: the LR rate was 29%, 13%, and 8% among women agedor =40, 41-60, andor =61 years (p0.001). Even in the case of complete excision, we observed a 24% rate of LR (6 of 25) in women40 years. Patients with negative, positive, or uncertain margins had a 7-year crude LR rate of 9.7%, 25.2%, and 12.2%, respectively (p = 0.008). RT reduced the LR rate in all subgroups, especially in those with comedocarcinoma (17% vs. 59% in the CS+RT and CS groups, respectively, p0.0001) and mixed cribriform/papillary tumors (9% vs. 31%, p0.0001). In the multivariate Cox regression model, young age and positive margins remained significant in the CS+RT group (p = 0.00012 and p = 0.016). Finally, the relative LR risk in the CS+RT group compared with the CS group was 0.35 (95% CI 0.25-0.51, p = 0.0001). Subsequent contralateral breast cancer occurred in 7.1% and 7.5% of the patients in the CS+RT and CS groups, respectively.Despite the absence of randomization, our results are extremely consistent with the updated National Surgical Adjuvant Breast Project B17 and European Organization for Research and Treatment of Cancer 10853 trials. We also noted that the LR risk was very high in women40 years and/or in the case of incomplete excision.

566 Background: T1N0M0 breast cancer (BC) are generally considered as carrying good prognosis and cancer-specific survival rates after 5 to 10 years are as high as 90 or 95% in many studies. However, they constitute a heterogeneous group and many studies identified biologically-defined at-risk patients within T1 BC. The objectives of our study were to describe the main characteristics of T1a, b, and c (11-15mm) BC and to identify prognostic factors for survival. Methods: We retrospectively collected the medical files of all patients diagnosed with BC who underwent sentinel lymph node biopsy (SLNB) between January 1999 and December 2008 in 13 French sites and examined overall survival (OS) and Relapse-free survival (RFS) in T1a, T1b and T1c 11-15 mm. Results: Among 8,100 women operated, 5,423 had T1 tumors (708 T1a, 2,208 T1b and 2,508 T1c 11-15mm). T1a differed significantly from T1b tumors with respect to several parameters : younger age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion (LVI), exhibiting a mix of favorable and poor prognosis factors. After a median follow-up of 60.5 months, OS rate was 97.6% (95CI: 97.1-98) at 60 months, 95.4%(94.5-96.4) at 84 months and 90.7% (85.2-96.4) at 120 months. No significant difference was observed between T1a, T1b and T1c tumors (p=0.335). RFS rates were 94% (95CI: 93.8-95.2), 92.1% [91.1-93.2] and 83.8% (77.6-90.5) at 60, 84 and 120 months respectively. RFS was significantly higher in T1b tumors (95.9%, 95CI: 95-96.9) as compared to T1a (93.2%, 91-95.4) or T1c tumors (93.8%, 92.8-94.9), p=0.0099. In multivariate analysis, SBR tumor grade, hormone therapy and LVI were independent prognostic factors for RFS, while hormone therapy and SBR grade were independently associated with OS. Conclusions: Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of adjuvant systemic therapy (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 breast cancer.

Background HER2 is overexpressed and amplified in approximately 15% of invasive breast cancers, and is the molecular target and predictive marker of response to anti-HER2 agents. In a subset of these cases, heterogeneous distribution of HER2 gene amplification can be found, which creates clinically challenging scenarios. Currently, breast cancers with HER2 amplification/overexpression in just over 10% of cancer cells are considered HER2-positive for clinical purposes; however, it is unclear as to whether the HER2-negative components of such tumors would be driven by distinct genetic alterations. Here we sought to characterize the pathologic and genetic features of the HER2-positive and HER2-negative components of breast cancers with heterogeneous HER2 gene amplification and to define the repertoire of potential driver genetic alterations in the HER2-negative components of these cases. Results We separately analyzed the HER2-negative and HER2-positive components of 12 HER2 heterogeneous breast cancers using gene copy number profiling and massively parallel sequencing, and identified potential driver genetic alterations restricted to the HER2-negative cells in each case. In vitro experiments provided functional evidence to suggest that BRF2 and DSN1 overexpression/amplification, and the HER2 I767M mutation may be alterations that compensate for the lack of HER2 amplification in the HER2-negative components of HER2 heterogeneous breast cancers. Conclusions Our results indicate that even driver genetic alterations, such as HER2 gene amplification, can be heterogeneously distributed within a cancer, and that the HER2-negative components are likely driven by genetic alterations not present in the HER2-positive components, including BRF2 and DSN1 amplification and HER2 somatic mutations. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0657-6) contains supplementary material, which is available to authorized users.