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Resume Objectif La reunion de concertation multidisciplinaire (RCP) a ete mise en place en France pour garantir une prise en charge homogene des patientes prises en charge en cancerologie en appliquant les referentiels en oncologie mammaire. Ces referentiels sont-ils reellement suivis dans les decisions emises par la RCP ? Patientes et methodes Nous avons analyse les 200 derniers dossiers de patientes operees en senologie dans le service. Nous avons cherche pour chaque dossier s’il avait ete presente a la RCP, a quel moment de la prise en charge et si la decision de RCP etait conforme aux referentiels utilises dans le service. Resultats Les 200 patientes avaient une moyenne d’âge de 56 ans (27–87 ans) et 145 (72,5 %) d’entre elles ont ete prises en charge pour un cancer invasif. Tous les dossiers ont ete discutes au moins une fois en RCP, 148 (74 %) en preoperatoire et 200 (100 %) en postoperatoire. Seules quatre decisions n’etaient pas conformes aux recommandations. Dans trois cas, la decision a ete motivee par le comite multidisciplinaire et dans un cas, la decision n’a pas ete motivee mais elle etait explicable. Discussion et conclusion Nous avons retrouve une bonne adequation des decisions de RCP avec les referentiels utilises dans notre centre. Certains dossiers compliques necessitent neanmoins d’adapter les referentiels aux particularites et aux souhaits de certaines patientes.

Background: Lymphocele is the principal post-operative morbidity following axillary node dissection. According to the literature, the incidence can vary from 4% to 89%. Encouraging results in terms of reducing postoperative lymphoceles as well as the volume and duration of drainage using octreotide LAR has been recently reported. Pasireotide LAR, a long acting drug designed to target multiple somatostatin receptors, was evaluated in this trial. Trial design: A phase II, two centers, randomized, double-blind, non-comparative pilot study was carried out in order to evaluate efficacy and safety of a single injection of pasireotide LAR 60 mg administered 7–10 days before scheduled mastectomy with axillary dissection surgery. This study included a parallel placebo arm to assess the natural course of the disease. Eligibility criteria: Adult female breast cancer patients planned to undergo a mastectomy (without reconstruction at the same time) and axillary node dissection. Specific aims: To assess the efficacy and safety of a single injection of pasireotide LAR 60 mg or placebo prior to mastectomy with axillary lymph node dissection surgery in reducing symptomatic lymphocele development. Symptomatic lymphocele was evaluated and was defined as: 1. total lymphocele drainage/aspiration volume (unique or iterative) >60 cc inclusive within the 28 days after surgery (excluding post-surgery drain) or; 2. a systematic aspiration volume at day 28 > 120 cc. Statistical methods: The statistical analysis was carried out sequentially after observing the absence of symptomatic lymphocele for each patient. It involves estimating the probability of a response in each group using a Bayesian design based on a beta-binomial model. The probability of response was considered random and its prior distribution was centered on 80% in the pasireotide group and 60% in the placebo group according to the investigators initial guesses. The distribution of the probability of response was updated after the observation of the patients included in the trial. Results: A total of 90 patients were included over 18 months: 42 in the treatment group and 48 in the placebo group. In the treatment group, the posterior mean estimation of the response rate (i.e. patients who did not experience a symptomatic lymphocele) was 62.4% (95% CI: 48.6%–75.3%) and 50.2% in the placebo group (95% CI: 37.6%–62.8%%). In the treatment group, one serious adverse event occurred in a patient with known insulin dependent diabetes requiring hospitalization for hyperglycaemia. Conclusion: A one time injection of pasireotide LAR to prevent symptomatic lymphocele development in women undergoing mastectomy with axillary dissection is promising. Further clinical studies are warranted. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-12.

Background. To reduce the incidence of microbial colonization of suture material, Triclosan- (TC-)coated suture materials have been developed. The aim of this study was to assess the incidence of suture-related complications (SRC) in breast surgery with and without the use of TC-coated sutures.Methods. We performed a study on two consecutive periods: 92 patients underwent breast surgery with conventional sutures (Group 1) and 98 with TC-coated sutures (Group 2). We performed subgroups analyses and developed a model to predict SRC in Group 1 and tested its clinical efficacy in Group 2 using a nomogram-based approach.Results. The SRC rates were 13% in Group 1 and 8% in Group 2. We found that some subgroups may benefit from TC-coated sutures. The discrimination obtained from a logistic regression model developed in Group 1 and based on multifocality, age and axillary lymphadenectomy was 0.88 (95% CI 0.77–0.95) (). There was a significant difference in Group 2 between predicted probabilities and observed percentages (). The predicted and observed proportions of complications in the high-risk group were 38% and 13%, respectively.Conclusion. This study used individual predictions of SRC and showed that using TC-coated suture may prevent SRC. This was particularly significant in high-risk patients.

Background Ko’s scoring system was developed to predict malignancy upgrades in patients diagnosed with atypical ductal hyperplasia by core needle biopsy. The Ko algorithm was able to identify a subset of patients who were eligible for exclusively clinical follow-up. The current study statistically investigated the patient outcomes to determine whether this scoring system could be translated and used safely in clinical practice. Methods We tested the statistical performance of the Ko scoring system against an external independent multicentre population. One hundred and seven cases of atypical ductal hyperplasia diagnosed by an 11-gauge biopsy needle were available for inclusion in this study. The discrimination, calibration and clinical utility of the scoring system were quantified. In addition, we tested the underestimation rate, sensitivity, specificity, and positive and negative predictive values according to the score threshold. Results The overall underestimation rate was 19% (20/107). The area under the receiver operating characteristic curve for the logistic regression model was 0.51 (95% confidence interval: 0.47–0.53). The model was not well calibrated. The lowest predicted underestimation rate was 11%. The sensitivity, specificity, positive predictive value, and negative predictive values were 90%, 22%, 20%, and 89%, respectively, according to the most accurate threshold proposed in the original study. Conclusion The scoring system was not sufficiently accurate to safely define a subset of patients who would be eligible for follow-up only and no additional treatment. These results demonstrate a lack of reproducibility in an external population. A multidisciplinary approach that correlates clinicopathological and mammographic features should be recommended for the management of these patients.

Background: Lymphocele is the principal post-operative morbidity following axillary node dissection. According to the literature, incidence can vary from 4 to 89%. Encouraging results in terms of reducing postoperative lymphoceles as well as drainage duration and volume using octreotide have been recorded recently. A new molecule, namely pasireotide, developed by Novartis Pharma AG, Basle Switzerland, is a somatostatin analog possessing high binding affinity to 4 of the 5 somatostatin receptors. Trial design: We are performing a prospective, randomized 1:1, double blind, multicenter trial against placebo with a Bayesian design. Eligibility criteria: any female patient scheduled for breast surgery with mastectomy and axillary node dissection indicated at the pre-surgical stage. Specific aims: The purpose of this trial is to assess the efficacy of a single pre-surgical injection of pasireotide LAR 60 mg im in reducing the postoperative incidence of symptomatic lymphoceles following mastectomy with axillary node dissection for breast cancer. Patients are followed up for 4 weeks Statistical methods: The statistical analysis will be carried out sequentially after observing the principal criterion (i.e. success is defined as a total volume of lymphocele following single or repeated aspiration ≤ 60 cc in the 28 days following surgery or a routine aspiration volume on the 28th day ≤ 120cc) of each patient included for each randomization group, with or without treatment. It involves estimating the probability of a response in each group using a Bayesian design based on a beta-binomial model. With the Bayesian approach, the response rate in each group (πi) is considered as a random variable, with a priori density focused on the anticipated response rate of 80% in the group receiving treatment and 60% in the non-treatment group, which will be sequentially updated as the observations are made according to a so-called a posteriori law. Present accrual and target accrual: The sample size consists of a total of 90 patients with 45 patients in the active treatment group and 45 patients in the placebo one. To date more than 50% of the patients have been included. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-07-01.

In breast conserving surgery (BCS), the usefulness to perform systematic cavity shaving is actively debated. Some investigators argued that systematic cavity shaving could avoid surgical re-excision and make diagnosis of unexpected multifocality. Others argued that usefulness of cavity shaving depends on volumes of resection. In this study one hundred patients undergoing BCS with systematic cavity shaving were included. Margins less than 3 mm were considered to be insufficient. We tested clinico-pathological characteristics in order to identify predictive model of cavity margin shaving utility and we sought to determine if cavity margin shaving usefulness depends on volumes of resection. We showed that cavity shaving avoids the need for re-excision in 24% of cases as well as diagnosis of multifocality in 6% of cases. However, the clinical usefulness of cavity shaving was not related to the volumes of resection.

Resume Objectifs La multifocalite dans les cancers du sein invasifs n’est pas reconnue comme un critere pronostique et n’est pas une indication de traitement adjuvant systemique. Par ailleurs, la methode la plus appropriee pour estimer la taille des tumeurs multifocales fait debat. Le but de cette etude est d’une part d’evaluer la valeur predictive et pronostique de la multifocalite, et d’autre part de comparer les differentes methodes utilisees pour estimer la taille de ces tumeurs. Patientes et methodes Entre 2001 et 2008, 1458 patientes ayant un cancer du sein invasif dont 16 % avec une tumeur multifocale ont ete incluses. Nous avons compare l’impact de la multifocalite sur le risque d’envahissement ganglionnaire, de recidives locales et a distance, et de survie globale. Trois methodes d’estimation de la taille des tumeurs multifocales ont ete comparees. Resultats La multifocalite est un facteur independant d’envahissement ganglionnaire. Les patientes ayant une tumeur multifocale ont un sur-risque d’environ 20 % d’envahissement ganglionnaire compare a une tumeur unifocale de meme taille. Considerer le diametre maximal du plus grand des foyers est la facon la plus appropriee d’estimer la taille tumorale d’un cancer multifocal. Discussion et conclusion On ne parvient pas a identifier de sous-groupe a faible risque d’envahissement ganglionnaire en cas de cancer multifocal. Ces resultats nous amenent a proposer d’etendre les indications de chimiotherapie adjuvante dans les cancers multifocaux, y compris en cas de tumeur de petite taille. Ces resultats devront etre valides par des essais multicentriques randomises.

Breast cancer is a frequent and heterogeneous disease. The choice of systemic treatments such as chemotherapy is based on predicting factors of response that did not much evolve. Preoperative chemotherapy provides an opportunity to directly assess tumor response to therapy. Predictors based on mathematical models could optimize those treatments. To go on this way, three different concepts have been developed to predict the preoperative chemotherapy complete response. Predictors based on clinical and pathological variables are specific of a tumor. They combine into mathematical models variables that have been previously identified as predicting the preoperative chemotherapy complete response. Predictors based on gene expression profile have been developed from groups of patients who received preoperative chemotherapy. They integrate multigene information to predict the tumor behaviour in front of several cytotoxic agents. Those predictors developed for each type of drug characterize the genetic chemoresistance of a tumor. In the same time, predictors of chemosensitivity developed from cell lines of diverse human cancer appeared. The authors established a genetic profile involved into chemoresistance and extrapolated the drug sensitivity for another type of cancer which was not represented, as breast cancer. All those predictors seem interesting but evolution of patients' characteristics and treatments induces a perpetual reassessment to optimize our predictive abilities.

Resume Objectifs Le prelevement du ganglion sentinelle (GS) est devenu le nouveau standard de l’exploration axillaire pour les tumeurs du sein invasives, unifocales, de petite taille. La decouverte de la multifocalite a posteriori, alors que la procedure du GS a ete realisee et que ce dernier est indemne de metastase, pose la question de la necessite ou non d’un curage axillaire (CA) complementaire. Patientes et methodes Il s’agit d’une etude retrospective portant sur 43 patientes ayant une tumeur multifocale decouverte en peroperatoire ou lors de l’examen histologique definitif et qui ont beneficie de la procedure du GS. Un examen anatomopathologique par coupes seriees en hemateine eosine safran (HES) et immunohistochimie (IHC) a ete realise pour chaque GS. Resultats La taille histologique moyenne de la tumeur la plus volumineuse etait de 16,8 mm (1 a 52 mm). Le nombre moyen de GS preleves par patiente etait de 2,07 (1 a 5). Seize patientes (34,1 %) avaient au moins un GS positif. Vingt-sept patientes ont eu un curage complementaire. La valeur predictive negative (VPN) etait de 100 % (intervalle de confiance [IC] a 95 % : 87,1 a 100 %) avec un nombre de faux-negatifs de zero. Aucune recidive axillaire n’est survenue apres un recul moyen de 20,8 mois (1–77). Discussion et conclusion La puissance de notre etude est insuffisante pour valider la procedure du GS en cas de decouverte secondaire du caractere multifocal d’une tumeur invasive. Cependant, le taux de faux-negatif de 0 % nous permet de penser que d’autres etudes prospectives avec un CA systematique permettraient de preciser si, dans ce contexte, le GS peut etre une alternative au CA.

In breast cancer, nine models have been developed to predict non SN status in patients with SN metastasis. Four models are nomograms: the Memorial Sloan-Kettering Cancer Center nomogram (MSKCC nomogram), the nomogram of Degnim et al. (Mayo nomogram), the nomogram of Pal et al. (Cambridge nomogram), and the nomogram of Kohrt et al. (Stanford nomogram). Three models are scoring systems: the Tenon score, the score from the M.D. Anderson Cancer Center (MDA score), and the score of Saidi et al. Finally, two are recursive partitioning tools developed by Kohrt et al. Before being used in routine, these models have to be validated in independent populations based on discrimination and calibration. However, the main issue is their clinical utility based not only on the low false negative rate but also its potential to discriminate patients with a low risk of non SN involvement. Several institutions have tested the MSKCC nomogram, with AUC ranging from 0.58 to 0.86. It was not validated by four studies which did not recommend its use even in patients with micrometastasis.The external validation of the Tenon score confirmed its relevance with an AUC of 0.82.

Summary Background: Occult invasive disease could be found at definitive histology in patients initially diagnosed with large ductal carcinoma in situ (DCIS). Sentinel lymph node (SLN) biopsy is a reliable and minimally invasive procedure providing axillary information and avoiding a second operation in this particular group of patients. The aim of our study was to assess the value of SLN biopsy in patients with large DCIS who are at highest risk for being upstaged to invasive carcinoma. Patients and methods: The study included 195 patients diagnosed with DCIS upon initial core biopsy and undergoing SLN biopsy. Many features were correlated with the presence of unsuspected invasive disease and positive SLN biopsy using univariate and multivariate analyses. Results: Of the 110 patients with pure DCIS, seven patients (6%) had a metastatic lymph node; 31 patients (16%) were found to have invasive disease upon final histology. Univariate analysis of predictors of unsuspected invasive carcinoma showed that patients having a preoperative biopsy that indicated DCIS with microinvasion (DCISM) or large DCIS were at a higher risk of invasive carcinoma after histological examination of the operative specimen. Of the 31 patients who were upstaged to invasive carcinoma at final histology, seven patients (22%) had a positive SLN biopsy. The analysis of predictors of positive SLN in our study shows that diffuse DCIS requiring mastectomy is the main risk factor for SLN metastasis. Conclusion: There are no real predictive factors for invasive disease in patients with an initial diagnosis of DCIS or DCISM. Our study supports the value of SLN biopsy in patients with a preoperative DCISM biopsy or patients with a large pure DCIS biopsy requiring mastectomy.

La chimiotherapie neoadjuvante (CNA) constitue maintenant une des methodes standards pour traiter les cancers du sein dans le but de permettre, dans certaines conditions, un traitement conservateur pour des tumeurs initialement avancees [1], [2]. Il est necessaire d’optimiser l’approche chirurgicale tant pour le traitement de la tumeur mammaire que pour le geste axillaire.

Objective The aim of this study was to assess the efficacy (response rate centered on 80%) of a somatostatin analog with high affinity for 4 somatostatin receptors in reducing the postoperative incidence of symptomatic lymphocele formation following total mastectomy with axillary lymph node dissection. Setting This prospective, double-blind, randomised, placebo-controlled, phase 2 trial was conducted in two secondary care centres. Participants All female patients for whom mastectomy and axillary lymph node dissection were indicated were eligible for the study, including patients who had received neo-adjuvant chemotherapy. Main exclusion criteria were related to diabetes, cardiac insufficiency, disorder of cardiac conduction or hepatic failure. Interventions Patients were randomised to receive one injection of either prolonged-release pasireotide 60 mg or placebo (physiological serum), which were administered intramuscularly 7 to 10 days before the scheduled surgery. The study was conducted in a double-blind manner. Primary and Secondary Outcome Measures The primary outcome measure was the percentage of patients who did not develop post-operative axillary symptomatic lymphoceles during the 2 postoperative months. Secondary endpoints were the total quantity of lymph drained, duration and daily volume of drainage and aspirated volumes of lymph. Results Ninety-one patients were randomised. Ninety patients were evaluable: 42 patients received pasireotide, and 48 patients received placebo. The mean estimated response rate were 62.4% (95% Credibility Interval [CrI]: 48.6%-75.3%) in the treatment group and 50.2% (95% CrI: 37.6%-62.8%) in the placebo group. Overall safety was comparable across groups, and one serious adverse event occurred. In the treatment group, one patient with known insulin-depe*ndent diabetes required hospitalization for hyperglycaemia. Conclusions With this phase 2 preliminary study, even if our results indicate a trend towards a reduction in symptomatic lymphocele, pre-operative injection of pasireotide failed to achieve a response rate centered on 80%. Pharmacokinetics analysis suggests that effect of pasireotide could be optimised. Trial Registration ClinicalTrials.gov NCT01356862

For ductal intraepithelial neoplasia, grade 1B, studies that predict breast cancer risk after an 11-gauge vacuum-assisted breast biopsy have yielded contradictory results. In order to identify a predictive model of breast cancer risk, we assessed the underestimation rate according to radiological and clinical findings.Our study involved 212 patients. We compared the area under the receiver operating characteristic curves and the clinical utility of a logistic regression and partitioning model.Overall upgrade to malignancy occurred in 42 (19.8%) out of the 212 cases. The area under the curve for the logistic regression and partitioning model were 0.65 (95% confidence interval=0.61-0.70) and 0.58 (95% confidence interval=0.54-0.62), respectively. The lowest predicted underestimation rate obtained with the logistic regression model was 9.5%.From this large series, we were unable to define any accurate safety model for breast cancer. Surgery should be thus recommended.

Objective: Detection of lymph node involvement in women with IB2–IIB cervical cancer could have a positive effect on survival. We set out to evaluate the incidence of pelvic and/or para-aortic lymph node involvement using the sentinel node (SN) biopsy and its impact on survival. Methods: From 2002 to 2010, 66 women with IB2–IIB cervical cancer underwent a pelvic and paraaortic lymphadenectomy with SN biopsy. Survival between groups according to lymph node status was evaluated. Results: Mean tumour size was 43.5 mm. At least one SN was detected in 69% of the 45 SN procedures performed. Sixteen of these patients had metastatic SN and the false negative rate was 20%. Metastatic pelvic SNs or non-SNs were detected in 33 patients (50%), including pelvic-positive nodes in 26 (40%), pelvic- and paraaortic-positive lymph nodes in seven (11%), and paraaortic skip metastases in two (6%). Positive paraaortic node was the sole determinant for disease-free survival (DFS) and overall survival (OS; P

Multidisciplinary meeting (MDM) should ensure a homogeneous management of the patients by following breast cancer guidelines. Are these guidelines really applied in MDM decisions?We reviewed the last 200 cases of patients operated in our department for breast cancer. We searched for each case if MDM had been consulted, at which step of the management and if the decision was in accordance with our guidelines.Mean age of the 200 patients was 56 (range 27-87)years old and 145 of them (72,5%) had an invasive breast cancer. All cases were presented to the MDM, 148 (74%) preoperatively and 200 (100%) postoperatively. Only four decisions did not follow our guidelines. In three cases, the decision was explained within the MDM report and in one case, the decision was not explained but could be understood.We found a significant relation between MDM decisions and our guidelines. However, complex cases require adapting the guidelines to the particularity and the wishes of the patients.

Les fils enduits de Triclosan® (antimicrobien) ont ete developpes afin de prevenir la colonisation microbienne des fils de suture.

En cas d’envahissement metastatique du ganglion sentinelle (GS) chez les patientes ayant un cancer du sein, un curage axillaire (CA) est recommande. Cependant, dans 40 a 70 % des cas, les ganglions non sentinelles (GNS) sont indemnes [1–4]. etre capable de predire l’absence de maladie residuelle dans les GNS en cas d’envahissement des GS permettrait d’eviter un curage axillaire chez ces patientes [1–9]. Des facteurs predictifs d’envahissement des GNS en cas de GS metastatiques ont ete mis en evidence dans de nombreuses etudes [1, 2, 4, 5, 10–13]. Cependant, les performances d’un facteur predictif pris isolement sont insuffisantes, y compris pour celles apparemment associees a un tres faible risque d’envahissement des GNS (micrometastase et a fortiori cellules isolees, taille tumorale inferieure a 10 mm, absence de rupture capsulaire, GS metastatique unique) [2, 5, 6, 10, 12, 13]. Dans ce contexte, l’utilisation de predicteurs clinicopathologiques peut s’averer tres utile pour selectionner les patientes ne necessitant pas de CA ou d’un traitement axillaire complementaire.

1. Le choix du traitement de la tumeur primitive, conservateur ou radical, repose sur la possibilite d’obtenir des marges saines et d’aboutir a un resultat cosmetique satisfaisant relayant au second plan des criteres comme la taille et la multifocalite. 2. L’extension du geste ganglionnaire se focalise de plus en plus sur des aspects pronostiques et d’indications therapeutiques. 3. La notion de risque influence de plus en plus les decisions.

Le but de cette etude etait de comparer deux nomogrammes pour predire la probabilite de reponse complete a la chimiotherapie neo-adjuvante (pCR) dans une cohorte independante de 200 patientes atteintes d’un cancer du sein. Le premier nomogramme utilise est celui de l’IGR/MDACC publie en 2005 par Rouzier et al. [1] et le second est un nomogramme publie par Colleoni et al. en 2010 [2].

The aim of this study is to compare two published nomograms, the “Institut Gustave Roussy/M.D. Anderson Cancer Center” (IGR/MDACC) and the Colleoni nomograms, in predicting pathologic complete responses (pCR) to preoperative chemotherapy in an independent cohort and to assess the impact of HER2 status. Data from 200 patients with breast carcinoma treated with preoperative chemotherapy were collected. We calculated pCR rate predictions with the two nomograms and compared the predictions with the outcomes. Sixty percent of the patients with HER2-positive tumors received trastuzumab concomitantly with taxanes. Model performances were quantified with respect to discrimination and calibration. In the whole population, the area under the ROC curve (AUC) for the IGR/MDACC nomogram and the Colleoni nomogram were 0.74 and 0.75, respectively. Both of them underestimated the pCR rate (P = 0.026 and 0.0005). When patients treated with trastuzumab were excluded, the AUC were excellent: 0.78 for both nomograms with no significant difference between the predicted and the observed pCR (P = 0.14 and 0.15). When the specific population treated with trastuzumab preoperatively was analyzed, the AUC for the IGR/MDACC nomogram and the Colleoni nomogram were poor, 0.52 and 0.53, respectively. The IGR/MDACC and the Colleoni nomograms were accurate in predicting the probability of pCR after preoperative chemotherapy in the HER2-negative population but did not correctly predict pCR in the HER2-positive patients who received trastuzumab. This suggests that responses to preoperative chemotherapy, including trastuzumab, are biologically driven and that a specific nomogram or predictor for HER2-positive patients has to be developed.

The sentinel lymph node (SLN) procedure is now used routinely for the staging of clinically node-negative patients with early breast cancer. Two identification techniques exist: colorimetric and isotopic. These can be used alone or in combination. The combined method is associated with an increased identification rate. However, allergic and adverse reactions to blue dyes have been reported. The objective of this review was to determine the incidence of such events and to discuss alternative approaches. The authors conducted a search of the MEDLINE and EMBASE databases for reports of anaphylactic responses to isosulfan blue dye and patent blue V dye. Allergic reaction to the dyes isosulfan blue and patent blue V is rare and the reported incidence varies between 0.07% and 2.7%. Methylene blue dye appears to be safer, with no cases of allergic events having been reported. However, allergy tests in some patients have proven that there is cross-reactivity between isosulfan blue dye and methylene blue dye. Even though the risk of an anaphylactic response is low, this raises questions about the usefulness of colorimetric detection of SLN and whether alternatives to the use of the isosulfan and patent blue V dyes, such as methylene blue, exist.

Breast cancer is a frequent and heterogeneous disease. The choice of systemic treatments such as chemotherapy is based on predicting factors of response that did not much evolve. Preoperative chemotherapy provides an opportunity to directly assess tumor response to therapy. Predictors based on mathematical models could optimize those treatments. To go on this way, three different concepts have been developed to predict the preoperative chemotherapy complete response. Predictors based on clinical and pathological variables are specific of a tumor. They combine into mathematical models variables that have been previously identified as predicting the preoperative chemotherapy complete response. Predictors based on gene expression profile have been developed from groups of patients who received preoperative chemotherapy. They integrate multigene information to predict the tumor behaviour in front of several cytotoxic agents. Those predictors developed for each type of drug characterize the genetic chemoresistance of a tumor. In the same time, predictors of chemosensitivity developed from cell lines of diverse human cancer appeared. The authors established a genetic profile involved into chemoresistance and extrapolated the drug sensitivity for another type of cancer which was not represented, as breast cancer. All those predictors seem interesting but evolution of patients' characteristics and treatments induces a perpetual reassessment to optimize our predictive abilities.

Background Lymph node status is an important prognostic factor and a criterion for adjuvant therapy in uterine cancers. While detection of micrometastases by ultrastaging techniques is correlated to prognosis in several other cancers, this remains a matter of debate for uterine cancers. The objective of this review on sentinel nodes (SN) in uterine cancers was to determine the contribution of ultrastaging to detect micrometastases. Methods Review of the English literature on SN procedure in cervical and endometrial cancers and histological techniques including hematoxylin and eosin (H&E) staining, serial sectioning, immunohistochemistry (IHC) and molecular techniques to detect micrometastases. Results In both cervical and endometrial cancers, H&E and IHC appeared insufficient to detect micrometastases. In cervical cancer, using H&E, serial sectioning and IHC, the rate of macrometastases varied between 7.1% and 36.3% with a mean value of 25.8%. The percentage of women with micrometastases ranged from 0% and 47.4% with a mean value of 28.3%. In endometrial cancer, the rate of macrometastases varied from 0% to 22%. Using H&E, serial sectioning and IHC, the rate of micrometastases varied from 0% to 15% with a mean value of 5.8%. In both cervical and endometrial cancers, data on the contribution of molecular techniques to detect micrometastases are insufficient to clarify their role in SN ultrastaging. Conclusion In uterine cancers, H&E, serial sectioning and IHC appears the best histological combined technique to detect micrometastases. Although accumulating data have proved the relation between the risk of recurrence and the presence of micrometastases, their clinical implications on indications for adjuvant therapy has to be clarified.

Occult invasive disease could be found at definitive histology in patients initially diagnosed with large ductal carcinoma in situ (DCIS). Sentinel lymph node (SLN) biopsy is a reliable and minimally invasive procedure providing axillary information and avoiding a second operation in this particular group of patients. The aim of our study was to assess the value of SLN biopsy in patients with large DCIS who are at highest risk for being upstaged to invasive carcinoma.The study included 195 patients diagnosed with DCIS upon initial core biopsy and undergoing SLN biopsy. Many features were correlated with the presence of unsuspected invasive disease and positive SLN biopsy using univariate and multivariate analyses.Of the 110 patients with pure DCIS, seven patients (6%) had a metastatic lymph node; 31 patients (16%) were found to have invasive disease upon final histology. Univariate analysis of predictors of unsuspected invasive carcinoma showed that patients having a preoperative biopsy that indicated DCIS with microinvasion (DCISM) or large DCIS were at a higher risk of invasive carcinoma after histological examination of the operative specimen. Of the 31 patients who were upstaged to invasive carcinoma at final histology, seven patients (22%) had a positive SLN biopsy. The analysis of predictors of positive SLN in our study shows that diffuse DCIS requiring mastectomy is the main risk factor for SLN metastasis.There are no real predictive factors for invasive disease in patients with an initial diagnosis of DCIS or DCISM. Our study supports the value of SLN biopsy in patients with a preoperative DCISM biopsy or patients with a large pure DCIS biopsy requiring mastectomy.

In breast cancer, nine models have been developed to predict non SN status in patients with SN metastasis. Four models are nomograms: the Memorial Sloan-Kettering Cancer Center nomogram (MSKCC nomogram), the nomogram of Degnim et al. (Mayo nomogram), the nomogram of Pal et al. (Cambridge nomogram), and the nomogram of Kohrt et al. (Stanford nomogram). Three models are scoring systems: the Tenon score, the score from the M.D. Anderson Cancer Center (MDA score), and the score of Saidi et al. Finally, two are recursive partitioning tools developed by Kohrt et al. Before being used in routine, these models have to be validated in independent populations based on discrimination and calibration. However, the main issue is their clinical utility based not only on the low false negative rate but also its potential to discriminate patients with a low risk of non SN involvement. Several institutions have tested the MSKCC nomogram, with AUC ranging from 0.58 to 0.86. It was not validated by four studies which did not recommend its use even in patients with micrometastasis.The external validation of the Tenon score confirmed its relevance with an AUC of 0.82.

Background: In two randomized trials, axillary lymph node dissection (ALND) did not significantly affect overall or disease-free survival of patients with a positive sentinel lymph node (SLN). These two trials closed early without the targeted enrollment questioning a lack of sufficient power. In retrospective observational studies, patients receive treatment according to tumor and patient (age, health status) factors and thus biasing the comparisons. Propensity score matching (PSM) analysis has been proposed as an alternative method to adjust for confounding factors with a statistical advantage over the standard methods of confounder adjustment. The method involves generation of a propensity score for each subject which is an estimate of the conditional probability of receiving a treatment given a set of known covariates. Propensity scores are used to reduce selection bias by equating groups based on these covariates. Objective: To evaluate whether patients with SLN metastasis of breast cancer who underwent complete ALND demonstrate improved survival in the Surveillance, Epidemiology and End Results database using a propensity score matching. Methods: The study population comprised 21073 patients. The 5-year cause-specific survival was tested, in order to examine the survival impact of complete lymphadenectomy by using propensity score matching analysis. The propensity scores to determine the conditional probability of receiving ALND were generated using logistic regression model. Patients were then matched using the propensity score by an optimal matching algorithm. Results: The PSM was based on age, race, region of diagnosis, tumor type and grade, tumor size, nodal status (micrometastasis vs macrometastasis) and hormone receptor status. It generated a balanced, matched cohort (3229 patients in each group) in which baseline characteristics were not significantly different. Five-year overall survival was 96.9% (95% CI 96.1–97.6%) in the ALND group and 94.0 (95% CI 92.6–95.4%) in the SLN biopsy alone group. The benefit of complete lymphadenectomy was significant: p = 0.028. Conclusion: Using PSM analysis, our results show evidence of benefit for ALND in case of metastatic sentinel lymph node. The results of randomized trials demonstrating no benefit for ALND may not been generalizable. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-14.