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Purpose Some children with extracranial germ cell tumors (GCT) relapse after or do not respond to first-line treatment combining chemotherapy and surgery, of whom very few experience long-term survival despite multimodal salvage treatment. Methods This prospective study, part of the French TGM95 Protocol for non-seminomatous GCT (NSGCT), included 19 (7%) children with malignant refractory or recurrent extracranial NSGCT who were studied to identify prognostic factors and determine the best salvage treatment. Results At the end of the first-line treatment, 10 and 9 children were in complete and incomplete remission, respectively. Events occurred within 2 years (5–23 months) after initial diagnosis. A progression was observed in 13 patients at least in one site initially involved. Two patients had a purely biological relapse (increase in isolated markers), and four patients had a purely metastatic relapse (brain location in three cases). After salvage treatment combining surgery and various types of chemotherapy (including high-dose chemotherapy (HDCT) in 10 cases), the 5-year event-free survival and overall survival rates were of 26% (95%CI: 9.6–46.8%) and 32% (95%CI: 12.9–52.2%), respectively. Patients who underwent complete surgery (or without any detectable tumor) had higher survival rate than patients who underwent partial surgery or for whom surgery was not feasible (P = 0.0003) at first relapse while this rate was similar between patients treated or not with HDCT. Conclusion In pediatric recurrent or refractory NSGCT, complete excision of the tumor appears essential. The role of HDCT remains debated. Pediatr Blood Cancer 2014;61:253–259. © 2013 Wiley Periodicals, Inc.

Background: Specific pathological and biological factors differentiating pure DCIS, DCIS with microinvasion (DCIS-MI) and DCIS with concomitant invasive ductal carcinoma (DCIS-IDC) are currently unknown. Identification of such factors would enable us to better understand the transition from an in situ to an invasive carcinoma and improve patient management for patients diagnosed with extensive DCIS. Methods: We previously performed a prospective surgical study demonstrating the benefit of performing upfront sentinel lymph node (SLN) biopsy in patients with extensive DCIS or DCIS-MI undergoing mastectomy. In that study, 196 DCIS and 31 DCIS-MI diagnosed on vacuum-assisted macrobiopsies underwent mastectomy and SLN biopsy. Final pathological status after mastectomy examination revealed 117 DCIS, 38 DCIS-MI, 69 DCIS-IDC, and in 3 cases no residual disease was found. The mastectomy specimens of 216 cases (111 DCIS, 37 DCIS-MI, 68 DCIS-IDC) were available for central pathological review and a TMA containing DCIS lesions of 214 cases (110 DCIS, 36 DCIS-MI, 68 DCIS-IDC) was performed. DCIS morphological features (histological size, nuclear grade, comedo necrosis, inflammation) and immunohistochemical factors (ER, PR, Ki-67 and Her2) were assessed in each of the three groups and compared using Chi2 or Wilcoxon tests. Results: Median histological DCIS sizes did not significantly differ between DCIS and DCIS-MI groups (70mm [4–160] and 60mm [4–180], respectively, p = 0.33), nor between DCIS and DCIS-IDC (70mm [4–160] and 65 mm [10–140], respectively, p = 0.98). DCIS nuclear grade was significantly higher in DCIS-MI compared to DCIS (p = 0.01), but there was no difference in nuclear grade between DCIS and DCIS-IDC (p = 0.22). Comedo necrosis was more often present in DCIS-MI compared to DCIS (p = 0.04), and no such difference was found between DCIS and DCIS-IDC (p = 0.81). Stromal inflammation surrounding DCIS was more often found in DCIS-MI and DCIS-IDC compared to DCIS (p = 0.03 and p < 0.001, respectively). DCIS-MI was more often ER-negative than DCIS (p = 0.009), and no such difference was found between DCIS and DCIS-IDC (p = 0.6). No other significant differences concerning PR and Her2 status or Ki-67 index were found between the 3 groups. Conclusions: In patients with extensive DCIS there are few morphological or current immunohistochemical factors differentiating in situ cases from those that have associated microinvasion or invasive ductal carcinoma. DCIS-MI cases have more aggressive histological features than DCIS. Stromal inflammation surrounding DCIS was the only feature distinguishing DCIS from DCIS-IDC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-14-03.

Aims: HER2 gene amplification is observed in up to 15% of breast carcinomas. In a rare subset of breast cancers classified as HER2-positive by immunohistochemistry and in situ hybridisation, HER2 overexpression and gene amplification are restricted to a subset of >30% but not all cancer cells. Here we sought to characterise the repertoire of gene copy number aberrations and somatic mutations in the HER2-positive and HER2-negative components of cases with heterogeneous HER2 overexpression and gene amplification. Material and methods: Cases diagnosed as HER2 positive but with >30% but Results: Twelve cases yielded sufficient DNA for aCGH analysis. Tumours were preferentially ER positive (83%) and of histological grade 3 (67%). The HER2-positive and HER2-negative components of all cases shared most of the copy number aberrations. A pairwise comparison of the genomic profiles of the two components from each case revealed that in ten of the twelve cases, copy number aberrations in addition to 17q12 amplification encompassing the HER2 gene locus were restricted to one of the two components. Exome sequencing of two cases suggested that the HER2-positive and HER2-negative components from each case harboured >30 somatic mutations in common, including identical TP53 somatic mutations in both components of each case. The HER2-negative component of one of the cases displayed a somatic mutation in NRG2, an ERBB receptor ligand, and the HER2-negative component of the other case harboured a mutation in PTTG1IP, a proto-oncogene with putative oestrogen receptor elements. Conclusions: Our results demonstrate that in HER2-positive breast cancers with heterogeneous HER2 gene amplification, the HER2-positive and HER2-negative components are clonally related. The distinct genomic profiles of HER2-positive and HER2-negative components, however, suggest that, at least in some of these cases, HER2 amplification may constitute a relatively late event in tumour evolution. Exome sequencing revealed mutations restricted to the HER2-negative components of HER2-positive tumours with heterogeneous HER2 overexpression/gene amplification, which may constitute potential drivers in the absence of HER2 overexpression/gene amplification. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD05-08.

Downregulating the leukocyte adhesion molecules expressed by endothelial cells that line tumor blood vessels can limit the entry of immune effector cells into the tumor mass, thereby contributing to tumoral immune escape. Egfl7 (also known as VE-statin) is a secreted protein specifically expressed by endothelial cells in normal tissues and by cancer cells in various human tumors. High levels of Egfl7 correlate with higher tumor grade and poorer prognosis. Here we show that expression of Egfl7 in breast and lung carcinoma cells accelerates tumor growth and metastasis in immunocompetent mice but not in immunodeficient mice. Tumors expressing Egfl7 were infiltrated relatively poorly by immune cells and were characterized by reduced levels of immunostimulatory cytokines [IFN-γ, interleukin-12 (IL-12)] and fewer endothelial adhesion molecules [intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)]. In vitro studies revealed that Egfl7 inhibited the expression of leukocyte adhesion molecules by endothelial cells, preventing lymphocyte adhesion. In contrast, Egfl7 did not exert any effects on immune cell activation. Human breast cancer lesions expressing high levels of Egfl7 also expressed less ICAM-1 and VCAM-1 in their blood vessels, also indicating an inverse correlation between expression levels of Egfl7 and IFN-γ. Thus, Egfl7 expression in tumors promotes tumor progression by reducing the expression of endothelial molecules that mediate immune cell infiltration. Our findings highlight a novel mechanism through which tumors escape immune control. Cancer Res; 71(23); 7176–86. ©2011 AACR.

The aim of this study was to prospectively evaluate the predictive value of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) to detect the absence of pathological response to preoperative chemotherapy in patients (pts) with breast cancer. 63 consecutive pts with non-metastatic, non-inflammatory breast cancer, eligible for neoadjuvant chemotherapy (3 FEC 100 followed by 3 Docetaxel) were enrolled. FDG-PET was performed just before the first as well as before the second course. Metabolic activity (tumour FDG uptake) was measured by standardised uptake value (SUV(max)). Pts were classified as non-responders (NR) when the decrease of SUV(max) in the primary tumour was less than 15% at the time of the second PET (EORTC 1999 criteria). The metabolic response in FDG-PET was correlated with WHO criteria (clinical evaluation and ultrasound and/or mammography) evaluated after three cycles, pathological complete response (pCR) after surgery (according to Sataloff classification) and 4-year relapse-free survival (RFS). The mean SUV(max) decrease according to histological response was -52 ± 21% in case of pCR (Sataloff A) and 25 ± 34% in other cases (Sataloff B + C + D). Out of the 16 pts with no PET response (SUV decrease less than 15%), only one had a clinical response after the third cycle, and no pCR was observed. The 4-year RFS rate was significantly longer for metabolic responders than for NR (respectively, 85 vs. 44%; P = 0.01). This prospective study shows that a decrease in the SUV of less than 15% after the first chemotherapy course is a very potent predictor for failure of neoadjuvant chemotherapy, especially of pCR. It is interesting to note that this was shown despite the fact that the chemotherapy regimen was changed after the third course.

International audience; En Europe, les patientes atteintes d’un cancer du sein invasif susceptibles de recevoir un traitement ciblé anti-HER2sont actuellement sélectionnées sur la base d’un test immunohistochimique (IHC). Les techniques d’hybridation in situ (HIS) doivent être utilisées pour l’évaluation des cas IHC ambigus (2+) et pour l’étalonnage de la technique IHC. Les patientes éligibles au traitement ciblant HER2présentent un statut HER2positif défini par un test IHC 3+ ou un test 2+ amplifié. Une détection correcte du statut HER2est indispensable à une utilisation optimale des thérapeutiques ciblées puisque leur efficacité est limitée aux patientes surexprimant HER2. Il est capital que l’évaluation du statut HER2soit optimisée et fiable. Ces recommandations du groupe d’étude des facteurs pronostiques IHC dans le cancer du sein (GEFPICS) détaillent et commentent les différentes étapes des techniques IHC et HIS, les contrôles utilisables et les règles générales de l’apprentissage de la lecture. Une fois acquis, ce savoir-faire doit être pérennisé par l’observation de règles de bonnes pratiques techniques (utilisation rigoureuse de témoins internes et externes et participation régulière à des programmes d’Assurance qualité [AQ])., Summary In Europe, patients who may benefit from an HER2 targeted drug are currently selected by immunohistochemistry (IHC). In situ hybridization (ISH) techniques should be used for complementary assessment of ambiguous 2+ IHC cases and for the calibration of the IHC technique. Eligibility to an HER2 target treatment is defined by an HER2 positive status being IHC test 3+ or 2+ amplified. Reliable detection of HER2 status is essential to the appropriate usage of HER2 targeted drugs because its specificity is limited to tumors overexpressing HER2. It is essential that the IHC evaluation of the HER2 status of a mammary carcinoma is optimized and reliable. This GEFPICS’ guidelines look over the different steps of the IHC technique, the controls and, the rules for interpretation. Once acquired, this knowledge must be perpetuated by the observation of rules of good technical practice (internal and external controls, quality assurance programs).

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.

Purpose The indications of adjuvant chemotherapy for patients with estrogen receptor (ER) –positive breast cancer are controversial. We analyzed the predictive value of Ki67, HER2, and progesterone receptor (PR) expression for the efficacy of docetaxel in patients with ER-positive, node-positive breast cancer. Patients and Methods Expression of Ki67, HER2, and PR was measured by immunohistochemistry in tumor samples from 798 patients with ER-positive breast cancer who participated in PACS01, a randomized trial that evaluated the efficacy of docetaxel. Risk reduction was evaluated using a Cox model adjusted for age, tumor size, nodal involvement, treatment arm, and biomarkers. The predictive value of biomarkers was assessed by an interaction test. Disease-free survival (DFS) was the primary end point. Results Ki67, HER2, and PR were expressed in 21%, 9%, and 62% of samples, respectively. Hazard ratios for relapse associated with docetaxel were 0.51 (95% CI, 0.26 to 1.01) in ER-positive/Ki67-positive tumors and 1.03 (95% CI, 0.69 to 1.55) in ER-positive/Ki67-negative tumors (ratio for interaction: 0.53; 95% CI, 0.24 to 1.16; P = .11). Five-year DFS rates were 81% (95% CI, 76% to 86%) and 84% (95% CI, 75% to 93%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with docetaxel and 81% (95% CI, 76% to 86%) and 62% (95% CI, 52% to 72%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with fluorouracil, epirubicin, and cisplatin. No trend for interaction was observed between docetaxel and HER2 (ratio for interaction: 0.83; 95% CI, 0.35 to 1.94; P = .66), nor between docetaxel and PR (ratio for interaction: 0.89; 95% CI, 0.47 to 1.66; P = .71). Conclusion Ki67 expression identifies a subset of patients with ER-positive breast cancer who could be sensitive to docetaxel treatment in the adjuvant setting.

Resume Les tumeurs ovariennes de type borderline representent 10 a 15 % de l’ensemble des tumeurs ovariennes. Leur pronostic est meilleur que celui des lesions invasives. Suspecter le diagnostic en preoperatoire sur les donnees de l’imagerie permet dans certains cas d’envisager un traitement conservateur. L’echographie permet d’affirmer l’origine ovarienne et la nature organique d’une lesion pelvienne. La specificite de cet examen est cependant limitee. L’IRM avec une injection dynamique de produit de contraste peut etayer le diagnostic en faveur d’une lesion maligne et dans certains cas en faveur d’une lesion borderline.

Resume Les sarcomes uterins sont des tumeurs rares qui representent moins de 4 % des tumeurs malignes de l’uterus. On differencie plusieurs sous-types histologiques : les sarcomes du chorion cytogene (Endometrial stromal sarcoma), dont l’origine est la muqueuse, les leiomyosarcomes d’origine musculaire, qui representent moins de 25 % des sarcomes uterins, et les carcinosarcomes d’origine mixte, qui sont les plus frequents. Le traitement associe chirurgie et radiotherapie ; une chimiotherapie adjuvante peut etre proposee dans les formes de haut grade. Le pronostic de ces lesions est sombre et depend de l’extension lesionnelle au diagnostic et de la qualite de l’exerese initiale. Le diagnostic est le plus souvent postoperatoire et les sarcomes representent 0,2 a 1 % des lesions operees avec le diagnostic preoperatoire de fibromes uterins. L’echographie en doppler ne permet pas de differencier les sarcomes uterins des fibromes. L’IRM, et notamment les sequences dynamiques apres injection de gadolinium, peut, elle, aider au diagnostic en montrant des lesions se rehaussant precocement apres injection avec une intensite de prise de contraste superieure a celle du myometre. L’existence de plages de necrose intralesionnelle est egalement tres specifique. Il semble licite de proposer une IRM aux patientes pouvant beneficier d’un traitement chirurgical conservateur de fibromes uterins, voire d’un traitement par voie basse, afin d’eviter un morcellement intra-abdominal d’un sarcome uterin, compte tenu de la gravite du pronostic dans ce cas.

International audience; Tumor blood vessels participate in the immune response against cancer cells and we previously used pre-clinical models to demonstrate that egfl7 (VE-statin) promotes tumor cell evasion from the immune system by repressing endothelial cell activation, preventing immune cells from entering the tumor mass. In the present study, the expression levels of egfl7 and that of ICAM-1 as a marker of endothelium activation, were evaluated in peritumoral vessels of human breast cancer samples. Breast cancer samples (174 invasive and 30 in situ) from 204 patients treated in 2005 were immunostained for CD31, ICAM-1 and stained for egfl7 using in situ hybridization. The expression levels of ICAM-1 and egfl7 were assessed in peritumoral areas using semi-quantitative scales. There was a strong and significant inverse correlation between the expression of ICAM-1 and that of egfl7 in CD31 + blood vessels. When the ICAM-1 score increased, the egfl7 score reduced significantly (P=0.004), and vice-versa (Cuzick's test for trend across ordered groups). In order to determine which gene influenced the other gene between egfl7 and ICAM-1, the expression levels of either gene were modulated in endothelial cells. Egfl7 regulated ICAM-1 expression while ICAM-1 had no effects on egfl7 expression in the same conditions. Altogether, these results provide further results that egfl7 serves a regulatory role in endothelial cell activation in relation to immune infiltration and that it is a potential therapeutic target to consider for improving anticancer immunotherapies.

Objective. Cervical carcinomas mainly spread via lymphatics, stepwise from pelvic to aortic and scalenic lymph nodes. Metastatic nodes are the major prognostic factor in this disease. When scalenic nodes are involved, cervical cancer is considered to be disseminated. Since there is a major discrepancy in reported percentages of metastatic scalene nodes in the literature (0 to 50%), we proceeded to systematic pretreatment scalene node biopsy and then evaluated the validity of this procedure. Methods. From January 1998 to May 2003, 72 patients with locally advanced cervical carcinoma and no suspicious paraaortic or scalenic nodes (respectively on magnetic resonance imaging and clinically) had a systematic surgical pretreatment lymph node evaluation (retroperitoneal laparoscopic infrarenal paraaortic lymph node dissection and left scalenic lymph node biopsy). Scalene biopsy was examined using hematoxylin/eosin stain and immunohistochemistry (KL1 antibodies). Results. Among the 72 patients, 20 were stage IB2, 4 were IIA, 14 were IIB, 4 were IIIA, 27 were IIIB, 1 was IVA and 2 had a recurrent cervical carcinoma. Fourteen women had histologically confirmed paraaortic metastases (11 macroscopic, 3 microscopic). No metastatic involvement of the scalene nodes was detected. Fifteen patients developed a recurrence within 12 months (3 to 19 months). None of the patients developed scalenic recurrence. Conclusion. Left scalene node biopsy does not appear to be mandatory in routine pretherapeutic lymph node evaluation of patients with advanced cervical carcinoma and no clinical suspicious nodes. It may be useful to prove disseminated disease in patients with suspicious clinical nodes or hot spots on PET-scan, if fine needle biopsy is unconclusive.

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.

Twenty-seven patients with recurrent soft-tissue sarcoma (STS) entered a multicenter study to determine the efficacy of the combination paclitaxel 200 mg/m 2 and epirubicin 75 mg/m 2 administered every 21 days. Patient characteristics included the following: 14 women and 13 men, median age of 52 years, 12 patients had local recurrence and 20 had metastasis. Eighteen patients had previously received chemotherapy for recurrent disease. The main grade III to IV hematologic toxicities were neutropenia (70%), anemia (3.7%), and thrombocytopenia (7.4%). Febrile neutropenia occurred in 5 patients (18.5%). Severe nonhematologic toxicities were rare. Two patients had a partial response (7.4%; 95% CI: 2.6-12.2%), with a median response duration of 3 and 5 months. Six patients had stable disease (22.2%), and 19 had progressive disease (70.5%). The median overall survival from study inclusion was 8 months. This study suggests the association paclitaxel-epirubicin does not increase the known activity of anthracycline in recurrent STS.

Background When invasive components are discovered at mastectomy for vacuum-assisted biopsy (VAB)-diagnosed ductal carcinoma in situ (DCIS), the only option available is axillary lymph node dissection (ALND). The primary aim of this prospective multicenter trial was to determine the benefit of performing upfront sentinel lymph node (SLN) biopsy for these patients. The secondary aim was to determine DCIS factors associated with microinvasion or invasion. Methods The SLN procedure was performed during mastectomy, and for positive SLN an ALND was performed during the same intervention. A tissue microarray containing DCIS lesions from the mastectomy specimens was subsequently performed. Results From May 2008 to December 2010, 228 patients were enrolled from 14 French cancer centers, including 192 eligible patients with pure DCIS on VAB and successful SLN procedures. ALND was avoided for 51 [67 %; 95 % confidence interval (CI), 56–77 %] of all the patients who had microinvasive DCIS or DCIS associated with invasive carcinoma at mastectomy and a negative SLN. Of the 192 patients, 76 (39 %) with VAB-diagnosed DCIS were upgraded after mastectomy to micro (n = 20) or invasive disease (n = 56). The rate of positive SLN for patients with DCIS on VAB was 14 %. High nuclear grade of DCIS was associated with greater risk of microinvasion and invasion, and HER2-amplified DCIS was associated with greater risk of invasion. Conclusions Underestimation of invasive components is high when DCIS is diagnosed by VAB in patients undergoing mastectomy. Upfront SLN for patients with VAB-diagnosed extensive DCIS avoids unnecessary ALND for two-thirds of patients with micro or invasive disease on mastectomy. Electronic supplementary material The online version of this article (doi:10.1245/s10434-015-4476-5) contains supplementary material, which is available to authorized users.

Procedure Infants with neuroblastoma (NB) were assessed according to INSS recommendations, including MIBG scan and extensive bone marrow staging to eliminate metastatic spread. Patients with unresectable tumour received chemotherapy, including two courses of carboplatin-etoposide (CE) and two of vincristine-cyclophosphamide-doxorubicin (CAdO). Post-operative treatment was to be given only in infants with MYCN amplification. Between 1990 and 1994, 52 consecutive children were registered. Results Among the 44 patients who received CE as a first course, the response rate was 66% and the primary could be removed in all children but one, who was in remission. The toxicity was mainly haematological and was always manageable. The 5 year overall survival (OS) and event-free survival (EFS) were 94 and 90 ± 8%, respectively, with a median follow-up of 48 months. The outcome of infants with no MYCN amplification was excellent; OS and EFS were, respectively, 97 and 94%. Conclusions Chemotherapy allows surgical excision and excellent outcome in infants with localised and unresectable NB. Less intensive Chemotherapy should be investigated in such patients. Med. Pediatr. Oncol. 36:247–250, 2001.© 2001 Wiley-Liss, Inc.

Some children with extracranial germ cell tumors (GCT) relapse after or do not respond to first-line treatment combining chemotherapy and surgery, of whom very few experience long-term survival despite multimodal salvage treatment.This prospective study, part of the French TGM95 Protocol for non-seminomatous GCT (NSGCT), included 19 (7%) children with malignant refractory or recurrent extracranial NSGCT who were studied to identify prognostic factors and determine the best salvage treatment.At the end of the first-line treatment, 10 and 9 children were in complete and incomplete remission, respectively. Events occurred within 2 years (5-23 months) after initial diagnosis. A progression was observed in 13 patients at least in one site initially involved. Two patients had a purely biological relapse (increase in isolated markers), and four patients had a purely metastatic relapse (brain location in three cases). After salvage treatment combining surgery and various types of chemotherapy (including high-dose chemotherapy (HDCT) in 10 cases), the 5-year event-free survival and overall survival rates were of 26% (95%CI: 9.6-46.8%) and 32% (95%CI: 12.9-52.2%), respectively. Patients who underwent complete surgery (or without any detectable tumor) had higher survival rate than patients who underwent partial surgery or for whom surgery was not feasible (P = 0.0003) at first relapse while this rate was similar between patients treated or not with HDCT.In pediatric recurrent or refractory NSGCT, complete excision of the tumor appears essential. The role of HDCT remains debated.

Melanoma has the highest rate of spread to the leptomeninges and the incidence of melanoma has been steadily rising. This article describes recent experience at the Lille University Hospital, between 2007 and 2011 and discusses the possibilities for treatment of leptomeningeal metastasis.Nine patients were diagnosed with leptomeningeal metastasis of melanoma. The standard criteria were used for the diagnosis. The treatment consisted of a combination of intrathecal chemotherapy, systemic chemotherapy and best supportive care.The overall median survival from the time of leptomeningeal metastasis diagnosis was eight weeks (range=1-168 weeks). In two cases, the median overall survival was 104 weeks. For these patients, there was a clear benefit in intrathecal chemotherapy combined with systemic treatment. No complication was observed.Despite a poor prognosis, treatment of melanoma leptomeningeal metastasis is needed in order to improve the quality of life, neurological progression-free survival and overall survival of patients.

Egfl7 (VE-statin) is specifically expressed by endothelial cells of normal tissues but its expression is deregulated in human cancers. Analysis of expression of Egfl7 protein and transcripts in 211 human breast cancer samples shows that Egfl7 is strongly expressed by breast tumor cells. Egfl7 expression is significantly higher in invasive ductal than in invasive lobular carcinoma. Expression of Egfl7 transcripts is also higher in lower SBR grade lesions and in lesions which are not associated with lymph node invasion. Within the invasive ductal carcinoma sub-population, expression of Egfl7 transcripts is correlated with the SBR score and with the ER+ status. High transcript and Egfl7 protein levels significantly correlate with the absence of axillary lymph node invasion. In lymph nodes, the levels of Egfl7 are correlated with the histological type of the primary lesions; they are higher in ductal than in lobular carcinoma. Egfl7 expression is thus associated with better prognosis factors and with the absence of lymph node invasion in human breast cancer lesions.

Approximately 2–5 % of patients with breast cancer (BC) develop leptomeningeal metastasis (LM). 103 consecutive patients with BC were diagnosed with LM and initially treated with intra-CSF liposomal cytarabine from 2007 to 2011 at a single institution. Correlations were determined with respect to patient characteristics and BC subtype with regard to overall survival (OS). At LM diagnosis, 61 % of patients had a 0–2 performance status (PS), the remaining 39 % were severely neurologically impaired. Regardless of PS, all patients received intra-cerebrospinal fluid (CSF) liposomal cytarabine as first-line treatment. Systemic treatment and radiotherapy were also given in 58 and 17 % of patients respectively as clinically appropriate. Second- (intra-CSF thiotepa) and third-line (intra-CSF methotrexate) treatment was administered in 24 and 6 patients respectively. Median OS was 3.8 months (range 1 day–2.8 years). In multivariate analysis, an initial combined treatment, a second-line treatment with intra-CSF thiotepa, an initial clinical response, and a non-‘ER/PR/HER2 negative’ BC were significantly associated with a better OS. Median OS in this heterogeneous retrospective case series was similar to that of previously observed BC patients treated with intra-CSF methotrexate suggesting intra-CSF liposomal cytarabine is a reasonable first choice therapy of BC-related LM.

Forty-two evaluable pediatric patients with a variety of recurrent primary brain tumors participated in a phase II ifosfamide trial. Their mean age was 10 years. All patients were treated with ifosfamide, 3 g/m2/day for 2 days every 2 weeks. Response was assessed on clinical and radiological criteria after at least 2 courses of therapy. The overall response rate was 12% (5/42). One complete and 2 partial responses were documented in 21 patients with medulloblastoma. A partial response was demonstrated in 1 patient with primitive neurectodermal tumor (PNET) and in 1 patient with ependymoma. No activity was observed in astrocytic tumors. Toxicity was primarily neurologic (16 out of 54 patients, 30%). Hematological toxicity, without severe morbidity, was encountered in 9% of courses (16/179). Ifosfamide, administered at this dose regimen has modest efficacy in the treatment of recurrent childhood medulloblastoma and ependymoma and appears inactive for gliomas. Further trials with other dose schedules are necessary to assess the activity of this drug. However, according to the neurotoxicity observed in our trial, we would not recommend building a protocol using ifosfamide for highly progressive brain tumors.

The incidence of leptomeningeal metastases (LM) in patients with breast cancer (BC) is increasing as a result of increased screening and improved patient survival. However, the median survival time after diagnosis of LM is between 5 weeks (without any treatment) and 5 months (for aggressively treated patients). In an attempt to identify clinicopathological risk factors for LM, we carried out a case-control study of 100 women with BC. Fifty patients with BC and LM were enrolled and an additional 50 patients with BC and no CNS metastases including leptomeningeal spread were selected as controls. Patients who had developed LM were selected between December 2006 and August 2008. The control group was matched for: age at diagnosis, year of diagnosis, and initiation of chemotherapy at BC diagnosis. The ILC type (P = 0.03), ER-negative (P = 0.01) and PR-negative status (P = 0.03), and initial M+ status at BC diagnosis (P = 0.008) tended to be more frequent in LM patients. These characteristics should lead to early appropriate assessments being performed in this targeted population when a neurological complaint appears, in order to detect LM as soon as possible.

Over the last two decades, chemotherapy has been introduced in protocols for patients with intracranial germinoma with the objective of reducing the volume and the dose of irradiation without compromising survival rates. The aim of this work is to critically analyze the pattern of relapse in a cohort of patients with nonmetastatic germinoma prospectively treated with chemotherapy followed by focal field radiation. Data of all germinoma patients registered in the French protocol for intracranial germ cell tumors between 1990 and 1999 were reviewed. The pattern of relapse, management, and outcome were analyzed in 10 of 60 patients who developed a recurrence after initial treatment. In 9 patients, the site of recurrence was local or loco-regional, notably in the periventricular area for 8. One patient only had isolated distant leptomeningeal relapse. The review of the sites of relapse suggests that most recurrences could have been avoided with a larger ventricular field of radiation. Treatment at first relapse included chemotherapy (10 patients), high-dose chemotherapy and stem cell transplant (8 patients), and/or radiation therapy (4 patients). Five patients experienced a second relapse. At a median follow-up of 72 months since the first relapse, 8 patients are alive in second or third remission. This review identified an excess of periventricular relapses when the focal field of radiation is used in the combined management of germinoma. These relapses are predominantly marginal or outside radiation fields. Ventricular field radiation appears a logical alternative to decrease the incidence of such relapses. Future trials should aim at better identifying patients who may benefit from local and ventricular radiation, respectively.

In Europe, patients who may benefit from an HER2 targeted drug are currently selected by immunohistochemistry (IHC). In situ hybridization (ISH) techniques should be used for complementary assessment of ambiguous 2+ IHC cases and for the calibration of the IHC technique. Eligibility to an HER2 target treatment is defined by an HER2 positive status being IHC test 3+ or 2+ amplified. Reliable detection of HER2 status is essential to the appropriate usage of HER2 targeted drugs because its specificity is limited to tumors overexpressing HER2. It is essential that the IHC evaluation of the HER2 status of a mammary carcinoma is optimized and reliable. This GEFPICS' guidelines look over the different steps of the IHC technique, the controls and, the rules for interpretation. Once acquired, this knowledge must be perpetuated by the observation of rules of good technical practice (internal and external controls, quality assurance programs).

International audience; Parvovirus H-1 (H-1 PV) preferentially replicates in malignant cells resulting in their death by cytolysis. It has often been considered a potential candidate for use in novel anticancer therapy. To evaluate its potential in a model of natural tumors, we assayed in vitro the effect exerted by H-1 PV on short-term cultures derived from breast tumor samples freshly excised from patients. Our results show that H-1 PV effectively kills tumor-derived cells, whereas normal tissue-derived cells showed no H-1 PV-induced cytopathic effects (CPE). We also determined that the H-1 PV sensitivity (up to 67% sensitive cultures) is related with the quantities of virus assayed. We further examined the expression and phosphorylation state of the parvoviral nonstructural protein 1 (NS1), known to be associated with parvoviruses-induced CPE. Both appear to be impaired in normal tissue-derived cells and resistant cultures. Finally, we show that H-1 PV sensitivity in cultures correlates significantly with higher tumor grades (Nottingham combined histologic grade 2 or 3). This report confirms that H-1 PV can efficiently induce CPE in primary breast tumor cells in vitro. It identifies tumor characteristics representing potential criteria for recruiting patients for clinical evaluation of H-1 PV antitumor effects.

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.

Cervical carcinomas mainly spread via lymphatics, stepwise from pelvic to aortic and scalenic lymph nodes. Metastatic nodes are the major prognostic factor in this disease. When scalenic nodes are involved, cervical cancer is considered to be disseminated. Since there is a major discrepancy in reported percentages of metastatic scalene nodes in the literature (0 to 50%), we proceeded to systematic pretreatment scalene node biopsy and then evaluated the validity of this procedure.From January 1998 to May 2003, 72 patients with locally advanced cervical carcinoma and no suspicious paraaortic or scalenic nodes (respectively on magnetic resonance imaging and clinically) had a systematic surgical pretreatment lymph node evaluation (retroperitoneal laparoscopic infrarenal paraaortic lymph node dissection and left scalenic lymph node biopsy). Scalene biopsy was examined using hematoxylin/eosin stain and immunohistochemistry (KL1 antibodies).Among the 72 patients, 20 were stage IB2, 4 were IIA, 14 were IIB, 4 were IIIA, 27 were IIIB, 1 was IVA and 2 had a recurrent cervical carcinoma. Fourteen women had histologically confirmed paraaortic metastases (11 macroscopic, 3 microscopic). No metastatic involvement of the scalene nodes was detected. Fifteen patients developed a recurrence within 12 months (3 to 19 months). None of the patients developed scalenic recurrence.Left scalene node biopsy does not appear to be mandatory in routine pretherapeutic lymph node evaluation of patients with advanced cervical carcinoma and no clinical suspicious nodes. It may be useful to prove disseminated disease in patients with suspicious clinical nodes or hot spots on PET-scan, if fine needle biopsy is unconclusive.

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.

Little is known about epidemiology of adults soft tissue and visceral sarcomas (ASTS). The frequency of previous cancers and associated genetic diseases has been analyzed out of 493 ASTS, treated between 1997 and 2002 at Oscar Lambret Cancer Center. Median age is 51, sex ratio is close to 1. Liposarcomas and malignant fibrous histiocytofibromas are the two main types (respectively 104 and 86 cases). Upper and lower limbs are the two main locations (respectively 176 and 75 cases). Fifteen patients had associated genetic disease, including 12 cases of Recklinghausen diseases. 7 out of those 15 patients have neurosarcoma. 30 patients have previous cancers, including 7 breast cancers, 3 lymphomas and 3 chronic lymphocytic leukemias. Four out of those 30 patients have two different previous cancers. 13 patients have radiation-induced sarcomas, after an average 10-year-period, and an average dose of 53 Gy. Undifferenciated sarcomas are the main histologic type (8/13), followed by angiosarcomas (2/13). Radiation-induced sarcomas are located in the chest wall (7/13), in pelvis (2/13) and head and neck (2/13). Those sarcomas are high grade (10 grade III tumours). ASTS epidemiology is complex with different risk factors depending on histologic type.

To perform sentinel node with local anaesthesia in the breast carcinoma without frozen section. So we used definitive histological and immunohistochemical results of sentinel node the day of conserving surgery with complete axillary lymph node dissection under general anaesthesia in case of involved nodes.Patients with a stage TNMT1 or N1, a multicentric breast cancer, a neoadjuvant chemotherapy, an allergy, an obesity or no detection of hot sentinel node were excluded. Patients in ambulatory surgery had scintigraphy 3 hours after injection of radiotracer. If we had a hot sentinel node, we applied Emla 5% cream on the areolar and axillary site and gave midazolam. We performed an intradermal injection of 2 ml of xylocaine with adrenaline above cancer and in the subareolar site in case of non-palpable cancer. With the same needle, we injected 2 ml of blue dye. We injected so 2 ml of xylocaine with adrenaline in the axillary hot spot. We completed local anaesthesia with 16 ml of xylocaine with adrenaline step by step on the route that intraoperative gamma probe showed us.We performed 17 patients (52.6 years [38-62]; body mass index = 23.7 [20-34.1], size of tumour = 10.8 mm [1-25]). We detected 100% of sentinel node. We had a secondary haematoma which was evacuated.Perform sentinel node under local anaesthesia is possible for patients with no obesity but radio tracer is absolutely necessary.

Background: Previous studies have suggested that pe­ ripheral blood stem cell (PBSC) transplantation has an advantage over autologous bone marrow transplantation. Objective: To compare the hematologic recovery and costs associated with PBSC transplantation with those as­ sociated with autologous bone marrow transplantation in patients receiving high-dose chemotherapy for solid tu­ mors or lymphomas. Design: Multicenter, randomized, controlled clinical trial. Setting: French Federation of Cancer Centers, located in cancer facilities or public hospitals with transplantation units. Patients: Children and adults with solid tumors or lym­ phomas who were candidates for high-dose chemotherapy. Interventions: Bone marrow or filgrastim-mobilized PBSCs. Measurement: The major end point was the duration of thrombocytopenia (platelet count < 50 x 10 9/L). An eco­ nomic evaluation of both types of transplantati on was done prospectively to measure costs and cost-effective­ ness. Results: 129 patients entered the trial; 64 had PBSC trans­ plantation, and 65 had bone marrow transplantation. The median duration of thrombocytope nia was 16 days in the PBSC group and 36 days in the bone marrow group (P < 0.001). All of the other clinical end points studied (time to last platelet transfusion, duration of granulocytopenia, number of transfusion episodes, and duration of hospital­ ization) favored PBSC transplantation. A cost analysis showed that total cost was decreased by 17% in adults and 29% in children with PBSC transplantation; thus, PBSC transplantation was clearly more cost-effective than bone marrow transplantation for both platelet and granulocyte recovery. Conclusion: Transplantation of PBSCs is associated with more rapid hematologic recovery than is bone marrow transplantation after high-dose chemotherapy for solid tumors or lymphomas. Furthermore, global costs are lower and cost-effectiveness ratios are better with PBSC trans­ plantation.

2070 Background: Around 5% of patients with breast cancers (BC) will develop leptomeningeal metastasis (LM). The incidence may increase. Methods: We reported the description and outcome of 112 consecutive BC patients diagnosed with LM in our institution from 2007 to 2011. Correlations between characteristics and overall survival (OS) were analyzed using usual statistical methods (Kaplan Meier, Log-rank, Cox model). Results: BC were invasive ductal carcinoma in 69.7%. Estrogen and progesterone receptors were detected in respectively 61.6 and 44.6%. HER2 expression was observed in 26%. 23% were triple negative. Median time between BC diagnosis and LM diagnosis was 44 months. At LM diagnosis, median age was 54 and median Performance Status (PS) was 2. CSF cytology and cerebrospinal MRI were positive in respectively 72,5% and 87%. 103 (92%) LM patients received IT liposomal cytarabine as 1st line of treatment (ventricular device in 47%). IT therapy could be associated with systemic treatment in 58% of the cases and cerebral radiotherapy for LM in 14% of the cases. Clinical response after 1st line treatment was observed in 57%, CSF response in 30,5%, MRI response in 62,5%. 24 patients received a 2nd line of IT thiotepa, 6 a 3rd line of IT methotrexate. The more significant prognostic factors (p

Aims: HER2 gene amplification is observed in 9% to 15% of breast carcinomas. According to current guidelines, cases with >10% but 10% but less than 100% of the cancer cells) i) to determine whether the HER2-positive and HER2-negative components are clonal and ii) to define the genomic differences between the HER2-positive and HER2-negative components. Material and methods: Fourty-four cases were collected consecutively among five French hospitals and for which initial reports mentioned HER2 heterogeneity. Diagnosis of HER2 heterogeneity was re-assessed by immunohistochemistry and chromogenic and/ or fluorescence in situ hybridization. Each component was microdissected (laser capture microdissection) from representative tissue sections stained with an anti-HER2 antibody (Herceptest). After DNA extraction, the DNA samples from the HER2-positive and HER2-negative components of each case were subjected to microarray-based comparative genomic hybridization (aCGH), using a platform with 50Kb resolution. Results: Out of 44 cases, the HER2-positive and HER2-negative components from 13 cases yielded DNA of sufficient quantity and quality and were subjected to aCGH analysis. Tumors were preferentially ductal carcinomas of no special type (83%), of histological grade 3, ER positive (83%), and lymph node positive (70%). In 11 of the 13 pairs (85%), the only significant difference among the genomic profiles was the presence of the region of amplification located at the 17q12-q21 locus encompassing the HER2 gene in the HER2-positive component. Unsupervised clustering of aCGH data demonstrated strikingly similar patterns of copy number profiles in different components of each tumour. In cases that were ER-positive, both the HER2-positive and HER2-negative components harboured alterations associated with ER-positive (luminal) carcinomas, such as gains of 1q+, losses of 16q, and amplifications of 8p12 and 11q13. Conclusions: Albeit rare, our results demonstrate that HER2 can be heterogeneously overexpressed and amplified in breast cancers, and this phenomenon appears to be more prevalent in ER-positive breast carcinomas. Based on the similarities of their genomic profiles, the HER2-positive and HER2-negative components from each case are clonal and are likely to have diverged relatively early in the tumor evolution. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 8. doi:1538-7445.AM2012-8

2089 Background: Around 5% of patients with breast cancer (BC) develop leptomeningeal metastasis (LM). Incidence of LM may increase. The aim of this study was to report the outcome of patients diag...

2075 Background: An increased incidence of leptomeningeal metastases (LM) is reported in breast cancer (BC), which is the predominant etiology of LM in solid tumors Our aim was to assess the signif...

e11540 Background: Neoadjuvant chemotherapy rarely induces a complete pathological response in LBC. Nevertheless, adjuvant chemotherapy is used in lobular as well as in other tumor types. Methods: ...

e21003 Background: The prognosis of pts 35 years of age or less is very poor. We studied a cohort of pts treated in the same institution for primary breast cancer. The aim of the study was to compa...

10551 Background: A pathological complete response (PCR) after neoadjuvant chemotherapy is observed in about 20% of the patients. A proteomic analysis was performed on plasma and tumor before treatment to evaluate its potential interest in the prediction of response. Patients: One hundred and forty-nine patients eligible for neoadjuvant chemotherapy were included in the study. Methods: Before treatment plasma and tissues (fine needle aspirations) were collected and frozen at –80°C and in liquid nitrogen respectively. The proteomic analysis was performed using the SELDI Technology. One μl of plasma and 10 μg of cytosolic proteins were loaded on proteinchip CM10 pH4, Imac-Cu, H50 arrays. Three acquisition protocols were used according to the mass range. The differences between protein levels in the two populations (responder and non responder) were detected using Mann Withney tests. Then plasma and tumor proteomic signatures, in relation to tumor response, were determined. Results: 28 patients out of 149 ex...

563 Background: To prospectively evaluate the predictive value of FDG-PET to detect the absence of clinical and pathological response to preoperative chemotherapy in patients (pts) with breast cancer. Methods: 63 consecutive pts with nonmetastatic, noninflammatory advanced breast cancer, eligible for neoadjuvant chemotherapy (3 FEC 100 followed by 3 docetaxel) were enrolled. Fifty-two were assessable (4 non eligible, 7 non evaluable). Median age of assessed pts was 49 years. There were 63% T2 and 37% T3, with 98% invasive ductal carcinomas. FDG-PET was performed before the first and the second course. Metabolic activity (tumor FDG uptake) was measured by standardized uptake value (SUVmax). Patients were classified as non responders (NR) when the decrease of SUVmax in the primary tumor was less than 15% at the time of the second PET (EORTC 1999 criteria). The metabolic response in FDG-PET was correlated with WHO criteria (clinical evaluation and ultrasound and/or mammography) evaluated after 3 cycles, path...

1123 Background: Around 5% of pts with breast cancer develop NM, which have a median overall survival (OS) of 5 months if treated and of 5 weeks if untreated. Pathological risk factors of NM are po...

Abstract #3012 Background: Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement. SLN positive patients(pts)with macro or micrometastasis require delayed axillary clearance. Intraoperative imprints have a good sensitivity for detection of macrometastasis but micrometastases are seldom diagnosed. Thus, we tested the intraoperative determination of axillary node metastasis according to the Rapid Gene Search Breast Lymph Node (BLN) Assay (Veridex) based on RT-PCR. Patients and methods:50 pts operated between September 17 and March 20 ,2008, had a SLN procedure. Lymph nodes were cut in 2 mm slices, and 1 out of 2 was examined with Rapid BLN Assay; the other one had intraoperative imprints and definitive histological assessement in paraffin-embedded sections including serial slices with hematoxilin eosine safran coloration and Cytokeratine AE1-AE3 immunochemistry. Results : 103 lymph nodes were examined with a median number of 2 SLN by pt. With Rapid BLN Assay, 12(9 pts) were positive and confirmed by histological interpretation on the other half for 11 (8 pts). 89 lymph nodes were negative (41 pts); in 1 (1 pt), isolated tumor cells (CTI) were detected in the other half at histological interpretation. Intraoperative imprints detected 4 macrometastases. One node declared positive at the intra-operative examination imprint corresponded to a granulomatous lesion after histological interpretation and Rapid BLN Assay was negative. Sensitivity was 31% for intraoperative imprints, 92% for Rapid BLN Assay and the histological examination of paraffin--embedded sections. The median time for intraoperative determination was 34 minutes for 1 SLN compared with 20 minutes for imprints. Conclusion: Given the high sensitivity of the rapid BLN assay, the excess duration of the procedure is acceptable for the surgeon. Furthermore, this procedure avoids a secondary axillary clearance in pts without intraoperative examination or with negative imprints and with metastases in SLN. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3012.

11016 Background: The MammoSite is a device that was developed with the goal of making breast-conserving surgery 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: From March 2003 to March 2005, 43 patients with T1 breast cancer were enrolled in a phase II prospective study. Twenty-five (58%) patients were qualified for HDR brachytherapy delivery. The median age was 72 years (range: 60–75). Twenty-five (58%) were treated with high-dose rate brachytherapy using the MammoSite applicator to deliver 34 Gy prescribed at 1 cm from the balloon surface in 10 fractions over 5 to 8 days. Results: The main disqualifying factor was pathologic sentinel node involvement. After a median follow-up of 13 months, there were no local recurrences. Seventeen (68%), 13 (52%), 7 (28%), 5 (20%) and 4 (16%) patients had erythema, seroma, inflammation, hematoma and infection, respectively. Only 2 patients developed telangiectasia. At 3 months breast erythema grade ≥ 2 was significantly correlated to cosmetic results (12.5% in the ‘good to excellent‘ versus 57% in the ‘poor to fair‘ group; p = 0.045). The strongest trend of excellent cosmetic outcome was observed in patients with skin spacing ≥ 19 mm (50%) compared to patients with < 19 mm (11%; p = 0.087). 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). Param Conclusions: To our knowledge, this is the first study since the initial FDA clinical study showing the feasibility of MammoSite brachytherapy procedure as a sole therapy in highly selected patients older than 60 years. This is also the first report on QoL during and after APBI using HDR brachytherapy with a MammoSite device. The toxicity and cosmetic results are in the range of other series. Higher range of skin spacing allowed a significant reduction of the risk of telangiectasia. QoL evaluation indicate that baseline scores were satisfactory. Changes concerned mainly emotional and social well-being. No significant financial relationships to disclose.

11033 Introduction: IBC has a very poor prognosis ; the first treatment is first primary chemotherapy, followed by surgery and radiotherapy. It has been shown that patients experiencing a complete pathological response haved a longer survival . The pathological response has thus to be carefully assessed. Material and Methods: The aim of this retrospective study was to determine whether there islook for a correlation between clinical response with (WHO criteria) and pathological response using Chevallier’s and Sataloff’s classifications. 56 successive patients received an anthracycline- based chemotherapy regimen for IBC before surgery; for all of these patients a pathological analysis had beenwas performed before chemotherapytreatment and after surgery. Alll the specimens werehave been reviewed by the same pathologist. Results: There is a very good correlation between the 2 pathological classifications fAmong the 56 patients, there were 3 complete clinical responses, which were also pathological complete responses according to both classifications.or the complete responders only. In all the other cases, no correlation wascould be found between the 3 classifications . It was particularly striking for all the 41 patients tumours classified grade 3 according to Chevallier who could be classified clinically (with WHO) or pathologically (with Sataloff) in either of the 4 groups from complete responseders to progressive disease . Overall , in this our series , 3 patients according to Chevallier and 11 according to Sataloff were complete pathological responders. Discussion: The lack of correlation between clinical and pathological classifications could be explained , at least in part, by the fibrosis often observed after primary chemotherapy. The differences observed between the 2 pathological classifications highlight the fact that there is no standard and that further research is neede in that perspective. [Table: see text] No significant financial relationships to disclose.

10666 Background: The aim of this study was to compare the two most frequently used pathological classifications to assess the response to chemotherapy (CT) in IBC. Methods: The pathological characteristics of 85 inflammatory breast cancers were reviewed. 52 patients (pts) had a post-CT mastectomy , 49 a tumor biopsy before CT and 16 both. Tumor types, grade, hormonal and Her status were evaluated before and after CT, when available. Results: Among 49 pts with initial biopsy, 1 had a high grade intraductular carcinoma and 48 an invasive carcinoma (42 ductular, 5 lobular, 1 mucinous). 27 (56%) invasive tumors were grade 3 and 21 (44%) grade 2, none was grade 1. Median value of mitotic index (Ki 67) was 23%. Hormone receptors (HR) were evaluable for 46 pts; 28 (61%) were negative. 13 (29%) out of 45 evaluable pts were Her2 3+. The pathological response was evaluated according to the Chevallier et Sataloff classifications in the 52 pts with post CT- mastectomy. According to Chevallier there were no grade 1(no microscopic invasive or in situ carcinoma) or 2 (microscopic in situ carcinoma without invasive carcinoma or axillary lymph node metastases), 44 (85%) were grade 3 (invasive carcinoma with fibrosis or sclerosis) and 8 grade 4 (no modification of initial tumor). There was no pathological complete response. According to Sataloff there were 4 grade TA (complete or nearly complete response), 15 (29%) TB (therapeutic response over 50%), 23 (44%) TC (therapeutic response above 50%), 10 TD (no evident therapeutic effect). There were 4 pathological complete responses out of 52 ( 8%). 16 pts had initial biopsy and post chemotherapy mastectomy. According to the OMS clinical classification there were 5 CR, 37 PR, 10 ST. Among the 4 pathological CR according to Sataloff (TA), 2 were CR and 2 PR. Conclusions: In our experience, there was a very poor correlation between the two pathological classifications and between pathological and clinical classifications. A clinical residual tumor can be due to fibrosis only. The classification used for the determination of the pathological response should always be given in clinical studies. No significant financial relationships to disclose.

763 Background: IBC is a rare clinical entity often considered together with Locally Advanced Breast Cancer(LABC); however, when compared to the LABC, the IBC has a poor prognosis; very few studies, often with a limited number of patients, have been published. Methods: 239 patients were diagnosed with IBC between 1985 and 1995. The diagnosis was ascertained by cytology in 89% of the patients on the breast tumor and in 55% on lymph nodes. A biopsy was done in 26% of the tumors. Histological features were studied at the time of surgery in the 60 patients operated after chemotherapy. Median age was 52.6 years, 57% were postmenopausal; most patients had a palpable breast tumor (89%) with a mean diameter of 7 cm and axillary lymph nodes (80%). 216 patients received chemotherapy (4 to 8 courses), 18 hormonotherapy only, followed by loco-regional treatment (surgery in 60 patients and radiation therapy in 219). DFS and OS were studied using Kaplan Meyer Method: Results: Response to chemotherapy was assessed clini...

605 Background: To define the value of biopathological parameters as prognostic and predictive markers in patients (pts) with node positive, operable breast cancer involved in the phase III trial P...