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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.

Ce chapitre porte sur la prise en charge diagnostique et therapeutique d’une recidive intramammaire homolaterale isolee d’un cancer du sein ayant eu initialement un traitement conservateur. Il exclut la surveillance apres traitement de la recidive locale. La recidive locale isolee homolaterale est definie comme une recidive intramammaire dans le sein traite (y compris avec atteinte de la peau par contiguite ou nodule isole sur la cicatrice initiale mais exclut les nodules de permeation et les recidives associees a une localisation ganglionnaire ou metastatique). La tumeur initiale et la recidive peuvent etre un cancer in situ et/ ou invasif.

The impact of cervical lymph node metastases and the optimal surgical management of the neck in patients with papillary thyroid carcinoma (PTC) remain controversial. The objectives of this retrospective study were to determine, in patients with PTC, the predictive factors and the impact on tumor recurrence rate of cervical lymph node involvement, and to evaluate the oncologic results and the morbidity of central neck dissection (CND). We reviewed the records of patients who had undergone surgical treatment for PTC at our institution between 1990 and 2000. A total of 368 patients (86 men and 282 women) were included in this study. Young age (p = 0.02), tumor size (p = 0.001) and extrathyroidal tumor extension (p = 0.003) were significant predictive factors of cervical lymph node metastatic involvement (multivariate analysis). Initial metastatic cervical lymph node involvement was identified as an independent risk factor of tumor recurrence (multivariate analysis, p = 0.01). Metastatic lymph node(s) were found in prophylactic CND specimens in 31% of the patients. CND increased the risk of postoperative hypocalcemia (p = 0.008) and of permanent hypoparathyroidism (p = 0.002). In conclusion, cervical lymph node metastatic involvement at the time of initial surgery is an independent risk factor of tumor recurrence. CND provided an up-staging of more than 30% of patients with a clinically N0 neck, but was associated with significant morbidity regarding parathyroid function.

Resume Objectif de l’etude Actuellement, la mastectomie represente le traitement de reference de la recidive locale du cancer du sein. Cependant, nous avons montre qu’un second traitement conservateur etait faisable en associant une nouvelle tumorectomie et une curietherapie interstitielle de bas debit de dose. Dans la presente etude, nous rapportons les resultats preliminaires d’un second traitement conservateur avec une curietherapie de haut debit de dose. Patientes et methodes De juin 2005 a juillet 2009, 42 patientes atteintes d’une recidive locale homolaterale d’un cancer du sein ont beneficie d’un second traitement conservateur. Apres tumorectomie et mise en place peroperatoire des tubes plastiques vecteurs, une scanographie dosimetrique a ete realisee pour delivrer une dose totale de 34 Gy en dix fractions et cinq jours dans le cadre d’un traitement ambulatoire. Le traitement systemique a ete discute au cas par cas. L’evaluation de la toxicite a utilise la Common Terminology Criteria for Adverse Events v3.0. Resultats Le suivi median etait de 21 mois (6–50 mois), l’âge median lors de la recidive etait de 65 ans (30–85 ans). Le delai median entre la tumeur primaire du sein et la recidive etait de 11 ans (1–35 ans). La recidive locale siegeait dans le lit tumoral dans 52 % des cas (22 patientes), dans le meme quadrant dans 33 % (14 patientes) et etait de siege inconnu dans 14 % (six patientes). La taille mediane de la recidive etait de 12 mm (2–30 mm). Les nombres medians de tubes plastiques vecteurs et de plans etaient respectivement de neuf (5–12) et deux (1–3). Le volume cible anatomoclinique (CTV) median etait de 68 cm3 (31,2–146 cm3). Le taux de second controle local etait de 97 %. Des effets secondaires ont ete notes chez 22 patientes (60 %). La fibrose cutanee et sous-cutanee representait 72 % de tous les effets secondaires observes. Conclusion Un second traitement conservateur radiochirurgical utilisant une curietherapie de haut debit de dose en cas de recidive locale homolaterale semble faisable, avec des taux de second controle local encourageants au prix d’une toxicite acceptable. Considerant qu’un essai randomise de non-inferiorite entre mastectomie et un second traitement conservateur serait difficilement realisable, quel niveau de preuve sera-t-il necessaire d’obtenir pour envisager un changement des pratiques ?

Objective To determine whether MRI assesses the size of ductal carcinomas in situ (DCIS) more accurately than mammography, using the histopathological dimension of the surgical specimen as the reference measurement. Materials and methods This single-center prospective study conducted from March 2007 to July 2008 at the Antoine-Lacassagne Cancer Treatment Center (Nice, France) included 33 patients with a histologically proven DCIS by needle biopsy, who all underwent clinical examination, mammography, and MRI interpreted by an experienced radiologist. All patients underwent surgery at our institution. The greatest dimensions of the DCIS determined by the two imaging modalities were compared with the histopathological dimension ascertained on the surgical specimen. The study was approved by the local Ethical Research Committee and was authorized by the French National Health Agency (AFSSAPS). Results The mean age of the 33 patients was 59.7 years (±10.3). Three patients had a palpable mass at clinical breast examination; 82% underwent conservative surgical therapy rather than radical breast surgery (mastectomy); 6% required repeat surgery. MRI detected 97% of the lesions. Non-mass-like enhancement was noted for 78% of the patients. In over 50% of the cases, distribution of the DCIS was ductal or segmental and the kinetic enhancement curve was persistent. Lesion size was correctly estimated (±5mm), under-estimated ( 5mm), respectively, by MRI in 60%, 19% and 21% of cases and by mammography in 38%, 31% and 31% ( p =0.05). Mean lesion size was 25.6mm at histopathology, 28.1mm at MRI, and 27.2mm on mammography (nonsignificant difference). The correlation coefficient between histopathological measurement and MRI was 0.831 versus 0.674 between histopathology and mammography. The correlation coefficient increased with the nuclear grade of the DCIS on mammography; this coefficient also increased as the mammographic breast density decreased. Conclusion MRI appears to assess the size of DCIS better than mammography by limiting the number of under- and over-estimations compared to histopathology findings.

Background: We analysed whether the level of human epidermal growth factor receptor-2 (HER-2) amplification significantly influenced either pathological complete response (pCR) or recurrence-free survival (RFS) and overall survival (OS) after trastuzumab-based neoadjuvant therapy. Methods: In all, 99 patients with an HER-2-amplified breast tumour treated with trastuzumab-based neoadjuvant therapy were included. Tumours were classified as low amplified (LA; 6–10 signals per nuclei) or highly amplified (HA; >10 signals). Pathological response was assessed according to Chevallier's classification (pCR was defined as grade 1 or 2). Median follow-up lasted 46 months (6–83). Cox uni- and multivariate analyses were performed. Results: In all, 33 tumour samples were LA and 66 were HA. The pCR in HA tumours was significantly higher than in LA tumours (55% vs 24%, P=0.005), whereas no association was found between the pCR rate and tumour stage, grade or hormone receptor status. In multivariate analysis, the pathological nodal status (P=0.005) and adjuvant trastuzumab (P=0.037) were independently associated with RFS, whereas the level of HER-2 amplification nearly reached statistical significance (P=0.057). There was no significant difference between LA and HA tumours for OS (P=0.22, log-rank). Conclusion: The level of HER-2 gene amplification significantly influenced pCR but not RFS or OS in non-metastatic breast cancer treated with trastuzumab-based neoadjuvant therapy. However, RFS in patients with HA tumours tended to be shorter.

Le traitement des cancers du sein localises repose sur la chirurgie conservatrice et la radiotherapie. Le risque de ces traitements est la recidive locale. De nombreuses etudes ont retrouve un impact entre recidive locale et marges d’exereses insuffisantes ou envahies qui restent cependant un facteur controverse, que ce soit dans sa definition, que dans son impact ou de son implication clinique. L’analyse des marges d’exerese doit prendre plusieurs facteurs en compte: le risque de recidive locale depend outre de la distance des marges de securitemais aussi de la localisation des marges, de la presence de carcinome in situ, du type d’envahissement local ou diffus, de l’âge de la patiente et les traitements adjuvants associes. La marge communement admise est de 2 mm. La reprise chirurgicale est indispensable s’il persiste des cellules cancereuses au niveau des berges d’exerese.

Resume Objectif Evaluer la qualite de la base Crisap de Paca Est, incluant les codes Adicap et les donnees sociodemographiques, recueillis par les structures anatomocytopathologiques (ACP) de Paca Est (Alpes-Maritimes, Monaco, Var, Haute-Corse). Methode Le code Adicap determine la lesion, l’organe, la technique utilisee. Un programme d’assurance qualite mis en place par le DSP inspire des recommandations IARC, evalue la qualite des donnees, corrige les incoherences et renseigne les donnees manquantes. Resultats En 2005 et 2006, 45 980 examens anatomopathologiques de tumeur maligne et in situ ont ete recueillis. Conformement au referentiel de qualite HAS–Afaqap 2005, l’identification du patient, du medecin prescripteur et ACP etaient disponibles. La date de lecture etait systematiquement renseignee. Une incoherence etait observee entre l’organe renseigne et le type histologique, l’âge et le sexe, respectivement, pour 0,32 % (n = 147), 0,04 % (n = 19) et 0,01 % (n = 3) des examens. En 2006, sur 9535 patients la date de naissance et le code postal etaient manquants, respectivement, dans 0,39 % (n = 37) et 22,46 % (n = 2142) des cas. Conclusion Le niveau de qualite du codage des tumeurs malignes et in situ en Adicap, par les medecins ACP du Crisap de Paca Est, est satisfaisant. Devenu en 2007 Crisap de Paca, cette base contribue desormais a l’evaluation des politiques regionales de lutte contre le cancer.

ObjectiveThe active transport of iodide into thyroid cells is mediated by the Na+/I− symporter (NIS) located in the basolateral membrane. Strong intracellular staining with anti-NIS antibodies has been reported in thyroid and breast cancers. Our initial objective was to screen tumour samples for intracellular NIS staining and then to study the mechanisms underlying the altered subcellular localization of the transporters.MethodsImmunostaining using three different anti-NIS antibodies was performed on paraffin-embedded tissue sections from 93 thyroid or breast cancers. Western blot experiments were carried out to determine the amount of NIS protein in 20 samples.ResultsUsing three different anti-NIS antibodies, we observed intracellular staining in a majority of thyroid tumour samples. Control immunohistochemistry and western blot experiments indicated that this intracellular staining was due to non-specific binding of the antibodies. In breast tumours, very weak intracellular staining was observed in some samples. Western blot experiments suggest that this labelling is also non-specific.ConclusionsOur results strongly indicate that the NIS protein level is low in thyroid and breast cancers and that the intracellular staining obtained with anti-NIS antibodies corresponds to a non-specific signal. Accordingly, to increase the efficiency of radiotherapy for thyroid cancers and to enable the use of radioiodine in the diagnosis and therapy of breast tumours, improving NIS targeting to the plasma membrane will not be sufficient. Instead, increasing the expression level of NIS should remain the major goal of this field.

Resume Objectif de l’etude Parmi toutes les techniques d’irradiation partielle et acceleree du sein, la curietherapie interstitielle de bas puis de haut debit de dose a ete la premiere utilisee. Les resultats preliminaires cliniques et dosimetriques de l’irradiation interstitielle partielle et acceleree du sein de haut debit de dose pratiquee au centre Antoine-Lacassagne de Nice ont ete analyses. Patientes et methodes De juin 2004 a mars 2008, 61 patientes, atteintes d’un carcinome mammaire non lobulaire T1-2 pN0, nouvellement diagnostique pour 37, en recidive pour 24, ont ete traitees par tumorectomie et ganglion sentinelle/curage axillaire avec mise en place peroperatoire de tubes plastiques vecteurs pour irradiation interstitielle partielle et acceleree du sein de haut debit de dose. L’etude dosimetrique (avec histogrammes dose–volume) a ete faite sur une scanographie realisee a deux a trois jours apres l’operation. Une analyse dosimetrique comparative a ete faite entre distributions de dose optimisee et non optimisee. Sur la base du conformal index (COIN), un nouvel indice a ete propose tenant compte a la fois de la conformite et de l’homogeneite de l’implant. Une analyse de l’impact du gradient de dose sur l’equivalence biologique de la curietherapie interstitielle de haut debit de dose a ete menee. Les analyses statistiques ont utilise le test t de Student, confirme par le test de Wilcoxon pour les effectifs inferieurs a 30. Resultats L’analyse dosimetrique comparative, entre distributions de dose optimisees et non optimisees, a montre que les indices de conformite obtenus apres optimisation ( conformal index , conformal number et D 90 % ) etaient tous significativement meilleurs que ceux obtenus sans optimisation. Cette amelioration de la conformite s’est faite au detriment d’une augmentation significative des volumes d’hyperdosage ( V 150 % et V 200 % ). Un Indice dit de « conformite et d’homogeneite », tenant compte du V 150 %, a permis de ponderer le conformal index . L’equivalence biologique de 34 Gy en dix fractions et cinq jours a ete calculee a 41,93 Gy pour un rapport α/β = 4 Gy mais a 75,76 Gy si le gradient de dose etait pris en compte. Conclusions La curietherapie interstitielle de haut debit de dose represente une des meilleures techniques d’irradiation partielle et acceleree du sein avec ses possibilites d’optimisation, de preservation de l’enveloppe cutanee et de determination du volume cible. De plus, l’impact du gradient de dose represente un atout majeur car une relation dose–effet a ete montree pour ce type de tumeur.

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.

To prospectively evaluate a compact portable 10-gauge handheld battery-operated biopsy system for stereotactic biopsy of microcalcifications. The ethics committee of the hospital approved this prospective multicentric study, and informed consent was obtained. Biopsy under stereotactic guidance was performed in 215 patients for 219 lesions consisting of microcalcifications without mass. The feasibility and the tolerance of the procedure were evaluated. The mean weight of the specimen was calculated. In patients with surgical diagnoses, the underestimation rate in biopsy diagnoses of atypical ductal hyperplasia and ductal carcinoma in situ were evaluated. The sampled specimens were separated according to the presence of calcifications on magnified specimen radiographs and to the probe the rotation number in order to evaluate the contribution of each rotation and the contribution of the specimen with and without calcifications on the radiographs. The macrobiopsy was feasible in 98.5% of the patients and was well tolerated in 82% of patients. It identified 4.6% invasive carcinomas, 18.5% ductal carcinomas in situ, 14.8% atypical ductal hyperplasias, 22.2% benign proliferative mastopathies and 39.8% benign non-proliferative mastopathies. The underestimation rate was 26.6% when an atypical ductal hyperplasia was diagnosed at biopsy, and 7.7% when a ductal carcinoma in situ was diagnosed. In the 77 patients with surgical correlation, the accurate diagnosis was obtained in specimens sampled during the first, second, and third in 69%, 9%, and 4% of the biopsies, respectively, and the analysis of specimens without microcalcification had an added value in 8% of patients. The compact portable battery-operated biopsy system can be used successfully for stereotactic biopsy of microcalcifications and constitutes a valid alternative to current systems.

Purpose: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are used to determine human epidermal growth factor receptor-2 (HER-2) status and patient eligibility for trastuzumab therapy. Using FISH and IHC, we analyzed the relationship between pathologic complete response to trastuzumab-based neoadjuvant therapy and level of HER-2 amplification in locally advanced breast cancer.Experimental Design: Breast biopsies from 93 HER-2–positive patients treated with trastuzumab-based neoadjuvant therapy were centrally collected and analyzed retrospectively for HER-2 amplification using FISH and HER-2 overexpression using IHC. Tumors were classified by FISH as no, low, or high amplification. Biopsies were reassessed centrally by IHC and graded 0, 1+, 2+, or 3+.Results: HER-2 status of tumor samples as assessed by FISH and IHC correlated: 16 no amplification (11 IHC 1+ and 5 IHC 2+), 27 low amplification (26 IHC 3+ and 1 IHC 2+), and 50 high amplification (all IHC 3+). Trastuzumab-based neoadjuvant therapy achieved pathologic complete response in 35 of 93 (37.6%) tumors. Pathologic complete response rate in low- and high-amplification tumors was significantly higher than in no-amplification tumors (44% versus 6%; P < 0.004). Pathologic complete response rate in high-amplification tumors was significantly higher compared with low-amplification tumors (56% versus 22%; P < 0.005). In the subgroup of low- plus high-amplification tumors, no correlation was found between pathologic complete response rate and IHC score, treatment regimen, T or N stage, tumor grade, or hormonal receptors.Conclusions: This is the first study to show positive correlation between level of HER-2 amplification assessed by FISH and rate of pathologic complete response to trastuzumab-based neoadjuvant treatment.

Purpose The objective of this study was to determine the value of magnetic resonance imaging (MRI) for the surgical planning of invasive lobular carcinoma (ILC)—a diagnostic challenge for radiologists. Materials and Methods Fifty-seven patients with histologically proven ILC were studied between 1998 and 2006. All patients underwent physical examination, mammography, ultrasound, and MRI. All anomalies detected were graded using the Breast Imaging Reporting and Data System (BI-RADS) classification, and careful research was made for the presence of multifocal/multicentric disease. Results On MRI, 72% of images were visualized as masses and 18% corresponded to non-mass-like enhancements. The size correlations, compared with histological findings, were .88 (MRI; P κ correlations for multifocality were .87 (MRI), .22 (ultrasound), and .22 (mammography). MRI had a sensitivity of 100% and a specificity of 87%. Forty-nine percent of therapeutic strategy cases were modified. Conclusion MRI is unquestionably valuable for the management of ILC. It provides the most accurate estimate of tumor size and is highly sensitive for multifocal disease. Its main drawback is its lack of specificity, which requires preoperative histological verification. MRI often justifies the modification of the initial therapeutic strategy, generally ruling out conservative procedures.

The aim of this study was to reexamine the prognostic role of tumor cell kinetics measured by S-phase fraction (SPF) and to establish its clinically relevant threshold values. SPF was determined by flow cytometry in a group of 920 consecutive breast cancer patients, all followed at our institute for 10 years (1988 to 1998). Mean age was 60.5 years (27–89 years). Median follow-up was 63 months (3–150 months). All patients had initial surgical treatment. SPF quartiles were: Q1=3.08%, median value = 5.98%, Q3=10.22%. A significant difference in overall specific survival was obtained between two populations divided by a cutoff at Q1 (p

Contexte. - La Federation nationale des centres de lutte contre le cancer (FNCLCC) et les Centres regionaux de lutte contre le cancer (CRLCC), en collaboration avec des partenaires des secteurs public (CHU, CHG), prive et certaines societes savantes ont entrepris, depuis 1993, d'elaborer des recommandations pour la pratique clinique en cancerologie : les Standards, Options et Recommandations» (SOR). L'objectif de l'operation SOR est d'ameliorer la qualite et l'efficience des soins aux patients atteints de cancer en fournissant aux praticiens une aide a la decision facilement utilisable. Objectifs. - Actualiser les recommandations pour la prise en charge des patients atteints de tumeurs malignes des glandes salivaires (lymphomes, sarcomes et melanomes exclus) valides en 1997. Ces recommandations concernent le diagnostic, la classification, le traitement et la surveillance de ces tumeurs. Methodes. - La methodologie d'elaboration des SOR repose sur une revue et une analyse critique des donnees de la litterature scientifique par un groupe d'experts pluridisciplinaire, permettant de definir, sur la base du niveau de preuve scientifique et du jugement argumente des experts, des « Standards », des « Options » et des « Recommandations ». Avant publication, les SOR sont revus par des experts independants. Resultats. - Cet article presente une mise a jour des recommandations concernant la radiotherapie. Les principales recommandations sont les suivantes: ○ la technique d'irradiation peut etre une irradiation conformationnelle avec dosimetrie previsionnelle 3D (avec ou non modulation d'intensite) ou une irradiation 2D; ○ pour les patients ayant eu une chirurgie complete, la radiotherapie postoperatoire aux photons n'est pas indiquee pour les tumeurs de bas grade de stades I et II (standard, niveau de preuve B2); elle est indique pour les tumeurs de haut grade de stades II, III et IV et dans les tumeurs de bas grade de stades III et IV (standard, niveau de preuve B2). La neutrontherapie n'est pas indiquee (standard, niveau de preuve D); ○ pour les patients operes ayant eu une chirurgie macroscopiquement ou microscopiquement incomplete, la radiotherapie postoperatoire est indiquee (standard). La neutrontherapie ou la radiotherapie aux photons peuvent etre proposees (options); ○ pour les patients non operables, la radiotherapie aux photons et la neutrontherapie peuvent etre proposees (options, niveau de preuve B2); ○ pour les patients non resecables et/ou recidivants, la neutrontherapie exclusive ou une chirurgie de reduction tumorale suivie d'une radiotherapie aux photons peuvent etre proposees (options, niveau de preuve C).

Background 18 Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer. Methods Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively. Results In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR = 0.47, P = 0.02) and overall-survival (HR = 0.38, P = 0.002). These results were confirmed in the independent cohort of 127 cancer patients. Conclusion Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H + symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.

Resume Objectif de l’etude. – Les carcinomes epidermoides non resecables de l’oropharynx et de l’hypopharynx conservent un pronostic defavorable a court ou moyen terme. Plus de 70 % des patients decedent dans les cinq ans de part l’evolution locoregionale. Nous rapportons pour ces tumeurs l’experience du centre Antoine Lacassagne d'une association concomittante de radiotherapie bifractionnee non acceleree et chimiotherapie. L’observance, la toxicite, la reponse tumorale, la survie et la presence d’eventuels facteurs cliniques pronostiques associes a ce traitement ont ete evaluees. Patients et methodes. – Quatre-vingt douze patients consecutifs ont ete pris en charge par ce protocole de mai 1992 a fevrier 2000. Tous etaient atteints d’un carcinome epidermoide pharynge non resecable de stade IV. La radiotherapie de la tumeur primitive et des ganglions satellites a ete delivree par deux faisceaux paralleles opposes, par les photons d’un appareil de telecobaltherapie ou d’un accelerateur de 4 a 6 MV, a raison de deux fractions de 1,2 Gy/j, cinq jours par semaine, sans interruption en cours de traitement. Une dose totale de 80,4 Gy a ete delivree aux cancers de l’oropharynx en 46 jours et de 75,6 Gy en 44 jours a ceux de l’hypopharynx. La chimiotherapie a consiste en une administration de deux a trois cycles, tous les 21 jours, de cisplatine a la dose de 100 mg/m 2 , et de 5-fluoro-uracile en perfusion continue sur cinq jours a raison de 750 mg/m 2 /j (1 er cycle), 430 mg/m 2 /j (2 e et 3 e cycles). Une attention particuliere a ete accordee aux soins complementaires en cours de traitement, tels que la mise en place systematique d’une nutrition enterale et un traitement de la mucite par laser de basse energie. Resultats. – En dehors de deux deces precoces lies au traitement, la toxicite aigue, bien que significative (mucite de grades III et IV de l’OMS : 89 % dont 16 % de grades IV, epithelite de grade III de l’OMS : 72 %, neutropenie de grade III et IV : 61 %) n’a pas ete une cause d’interruption de traitement de plus d’une semaine, grâce notamment aux soins complementaires. Le taux de reponse complete a six mois etait de 74 %. Les taux actuariels de survie globale etaient respectivement a un et deux ans de 72 et 50 % avec un recul median de 17 mois. Les facteurs pronostiques de la survie globale etaient l’etat general (taux de survie globale a trois ans de 71 % si l’indice de Karnofsky du patient etait entre 90 et 100 %, 30 % s’il etait de 80 %, 0 % enfin s’il etait entre 60 et 70 %, p = 0,0001) et la localisation tumorale (taux de survie globale a trois ans de 28 % en cas de cancer de l’hypopharynx, 37 % en cas de cancer du panpharynx et 55 % en cas de cancer de l’oropharynx, p = 0,009). Conclusion. – L’analyse de ces resultats a confirme l’efficacite de la radiotherapie bifractionnee non acceleree concomitante a la chimiotherapie par cisplatine et 5-fluoro-uracile sur ce type de tumeur particulierement evoluee. Quant a l’etat general du patient avant traitement, seule une prise en charge nutritionnelle efficace peut conduire a une optimisation des conditions de realisation et de succes du protocole.

The aim of this study was to define the ultrasonographic (US) features of the invasive lobular carcinoma (ILC). For this purpose, the clinical histories and the mammographic and sonographic findings observed in 102 patients affected by documented ILC were retrospectively reviewed, and the role and value of US in the diagnosis of palpable and nonpalpable breast tumors were evaluated. At US, five proven tumors were not visualized (sensitivity: 95%), while the remaining 97 showed sonographic images that are considered typically malignant: irregular heterogenic, hypoechoic irregular masses in 94 cases, which were associated with posterior shadowing in 87. The presence of only a posterior shadowing was observed in three cases. There were 16 subclinical tumors, and in two of the four in which a mammography showed an indeterminate lesion, US demonstrated a malignant pattern. All the palpable tumors that were not detected mammographically were demonstrated by US. In 13 of the 102 patients (12.7%), the correct diagnosis of malignancy was established by US. On the basis of the data obtained, it is felt that because of its sensitivity and high specificity for malignancy, US plays a very important role in the diagnosis of ILC, whenever in a patient with positive clinical findings, the mammography is negative or the mammographic features are equivocal.

The long-term prognostic value of tumoural MDR1 and MRP, along with p53 and other classical parameters, was analysed on 85 node-positive breast cancer patients receiving anthracycline-based adjuvant therapy. All patients underwent tumour resection plus irradiation and adjuvant chemotherapy (the majority receiving fluorouracil–epirubicin–cyclophosphamide). Median follow-up for the 54 alive patients was 7.8 years. Mean age was 53.7 years (range 28–79) and 54 patients were post-menopausal. MDR1 and MRP expression were quantified according to an original reverse transcription polymerase chain reaction multiplex assay with colourimetric enzyme-linked immunosorbent assay detection(β2-microglobulin as control). P53 protein was analysed using an immunoluminometric assay (Sangtec). MDR1 expression varied within an 11-fold range (mean 94, median 83), MRP within a 45-fold range (mean 315, median 242) and p53 protein from the limit of detection (0.002 ng mg−1) up to 35.71 ng mg−1(mean 1.18, median 0.13 ng mg−1). P53 protein was significantly higher in oestrogen receptor (ER)-negative than in ER-positive tumours (P = 0.039). The higher the p53, the lower the MDR1 expression (P = 0.015, r = –0.27). P53 was not linked to progesterone receptor (PR) status, S phase fraction, or MRP. Significantly greater MDR1 expression was observed in grade I tumours (P = 0.029). No relationship was observed between MDR1 and MRP. Neither MDR1 nor MRP was linked to ER or PR status. Unlike MDR1, MRP was correlated with the S phase: the greater the MRP, the lower the S phase (P = 0.006, r = –0.42). Univariate Cox analyses revealed that MDR1, MRP, p53 and S phase had no significant influence on progression-free or specific survival. A tendency suggested that the greater the p53, the shorter the progression-free survival (P = 0.076 as continuous and 0.069 as dichotomous). © 2000 Cancer Research Campaign

We studied the polymorphisms m1 (Msp1 restriction site) and m2 (codon Val substitution) of CYP1A1 gene and the copy number of glutathione S-transferase mu1 (GSTM1) gene on 487 DNA of breast cancer primary tumours from Caucasian group. Tumours of patients aged 55 years and under at diagnosis presented a great proportion of wild m1 (-/-) genotype; 83.6% vs. 69.5% (p < 0.0006), and a higher percentage of copy number of GSTM1 equal or under one copy; 65.2% vs. 53.4% (p < 0.011) for older patients m1 and m2 variants are closely linked (p < 0.0000). Tumour with a low copy number of GSTM1 is correlated with high histological grading (p < 0.01) and high Cathepsin D concentrations (p < 0.02). The combinations of different genotypes showed that association wild m1 (-/-) genotype and copy number of GSTM1 inferior or equal to one copy is correlated with an early onset of breast cancer primary tumour 44% vs. 6.4% for m1 (-/+) or (+/+) genotype and copy number of GSTM1 superior to one (p < 0.0000). The CYP1A1 gene wild form seems to be associated with early cancer development in Caucasian patients.

La recherche du ganglion sentinelle (GS) dans les carcinomes canalaires in situ (CCIS) du sein est le plus souvent negative avec 2 % d’atteinte ganglionnaire. Cependant, il n’est pas rare en cas mastectomie realisee dans le cadre d’un CCIS diagnostique par macrobiopsie, de decouvrir sur la piece operatoire un carcinome infiltrant ou micro-infiltrant.

We have investigated, by image analysis, the cell cycle expression of estrogen receptors (ER) on MCF-7 cell line and on MCF-7 xenografts. The results demonstrate, in vitro as well as in vivo, an increase of ER concentration during the G0/G1-phase, followed by a decrease during the S-phase until the late S-phase where a rapid increase was noted. These results confirm that estrogens are involved in the DNA synthesis since ER is expressed in vivo at a maximal level in the late G1. In presence of saturating concentrations of 17 beta-estradiol, the mean ER concentration in G0/G1 phase is significantly decreased compared with the control cells cultured in estrogen-deprived medium. This indicates that 17 beta-estradiol down-regulates ER preferentially in the G0/G1 phase. These data suggest that ER in S and G2/M phases is unable to interact with its ligand. Consequently, estrogens may have no effects on the entry of cells in mitosis. Finally, after long-term tamoxifen treatment of MCF-7 xenografts, a tamoxifen-resistant tumor was developed which was characterized by a change in the profile of ER concentration during the G0/G1 phase. In conclusion, it is possible that the differences in cell cycle distribution of ER could be correlated with different phenotypes of breast cancer and also with different clinical phases of tumoral evolution. However, it remains to be known what is the clinical significance of the ER cell cycle expression in relation to tumor aggressiveness and survival.

Dans le cancer du sein, de nombreux facteurs pronostiques et predictifs sont accessibles, ces facteurs permettent d’evaluer l’evolution de la maladie mais aussi d’affiner le choix d’une prise en charge therapeutique. Le statut d’envahissement ganglionnaire (positif ou atients) est un des plus importants parametres pronostiques independants [1]. Les patientes montrant un envahissement ganglionnaire negatif presentent une maladie a bas ou moyen risque alors que les malades montrant au moins un ganglion envahi sont d’emblee considerees a moyen ou haut risque [2]. Le statut ganglionnaire doit etre considere comme un facteur pronostique » pur « et non comme un facteur predictif permettant de predire la reponse au traitement

A new human cell line, CAL 78, derived from a dedifferentiated chondrosarcoma of the muscle of the thigh has been established in culture. Fibroblastoid morphology, vimentin expression and lack of epithelial antigens are in agreement with mesodermic origin of these cells. The xenograft of CAL 78 cells in nude mouse showed the characteristics of hyaline cartilaginous differentiation. Cytogenetic changes were numerous and complex, all the metaphases were tetraploid and no alterations described by other authors have been found. CAL 78 constitutes an appropriate model to evaluate efficiency of a new therapy for chondrosarcomas. Moreover, this cell line may be used to study some stage of chondrocytic differentiation.

Purpose To assess early clinical results and evaluate patient satisfaction in case of second conservative treatment (2nd CT) combining lumpectomy plus high-dose rate (HDR) interstitial brachytherapy for patients (pts) presenting with ipsilateral breast cancer recurrence (IBCR). Methods and Materials From June 2005 to July 2009, 42 pts presenting with an IBCR underwent a second lumpectomy with intraoperative implantation of plastic tubes in the tumor bed. After performing the dose distribution analysis on the postimplant CT scan, a total dose of 34 Gy in 10 fractions over 5 consecutive days was delivered. Toxicity evaluation was based on the Common Terminology Criteria for Adverse Events v3.0 criteria. Applying a visual analogic scale (VAS) analysis, patient satisfaction regarding cosmetic result and 2nd CT possibility was performed after the end of brachytherapy. Results Median followup was 21 months (range, 6–50 months) and median age at the time of local recurrence was 65 years (range, 30–85 years). Median delay between primary and recurrence was 11 years (range, 1–35 years). Median recurrence tumor size was 12 mm (range, 2–30 mm). Median number of plastic tubes and planes were nine (range, 5–12) and two (range, 1–3), respectively. Median clinical target volume was 68 cc (range, 31.2–146 cc). Second local control rate was 97%. Twenty-two pts (60%) developed complications. Cutaneous and subcutaneous fibrosis was the most frequent side effect. Median VAS satisfaction score regarding cosmetic result was 7 of 10 (range, 4–9), whereas median VAS satisfaction score for 2nd CT was 10 of 10 (range, 8–10). Conclusion A 2nd CT for IBCR using high-dose rate brachytherapy seems feasible with encouraging results in terms of second local control with an acceptable toxicity. Patient satisfaction regarding the possibility of second breast preservation should be considered.

Currently, radical mastectomy represents the gold standard for ipsilateral breast cancer recurrence. However, we already showed that a second conservative treatment was feasible combining lumpectomy plus low-dose rate interstitial brachytherapy. In this study, we reported the preliminary results of a second conservative treatment using a high-dose rate brachytherapy.From June 2005 to July 2009, 42 patients presenting with an ipsilateral breast cancer recurrence underwent a second conservative treatment. Plastic tubes were implanted intra-operatively at the time of the lumpectomy. After a post-implant CT scan, a total dose of 34 Gy in 10 fractions over 5 consecutive days was delivered through an ambulatory procedure. The toxicity evaluation used the Common Terminology Criteria for Adverse Events v3.0.The median follow-up was 21 months (6-50 months), median age at the time of the local recurrence was 65 years (30-85 years). The median delay between the primary and the recurrence was 11 years (1-35 years). The location of the recurrence was in the tumor bed for 22 patients (52.4%), in the same quadrant for 14 patients (33.3%) and unknown for six patients (14.3%). The median tumor size of the recurrence was 12 mm (2-30 mm). The median number of plastic tubes and plans were nine (5-12) and two (1-3) respectively. The median CTV was 68 cm(3) (31.2-146 cm(3)). The rate of second local control was 97%. Twenty-two patients (60%) experienced complications. The most frequent side effect consisted in cutaneous and sub-cutaneous fibrosis (72% of all the observed complications).A second conservative treatment for ipsilateral breast cancer recurrence using high-dose rate brachytherapy appears feasible leading to encouraging results in terms of second local control with an acceptable toxicity. Considering that a non-inferiority randomized trial comparing mastectomy versus second conservative treatment could be difficult to perform, what proof level will be necessary to achieve in order to change the medical procedures?

Pendant longtemps, la mastectomie etait le traitement de reference pour les cancers du sein, quel que soit le volume tumoral. Il s’agit cependant d’un traitement mutilant, ayant un impact majeur sur l’image corporelle et la sexualite (1, 2). L’equivalence entre mastectomie et traitement conservateur (associant chirurgie et radiotherapie) a ete longue a prouver (3, 4, 5) pour les tumeurs de moins de 3 cm. Cette attitude conservatrice represente desormais le standard de prise en charge pour des cancers du sein classe T1–2.

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.

Background: Treatment of metastatic breast cancer (MBC) remains palliative. Patients with MBC represent a heterogeneous group whose prognosis and outcome may be dependent on host factors. The purpose of the present study was dual: first, to draw up a list of factors easily available in everyday clinical practice requiring no sophisticated or costly methods and second, to provide results from a large cohort of women who underwent diagnostic and treatment at a single institution. Patients and methods: From 1975 to 2005, a total of 1038 women with MBC during their follow-up were included in this retrospective analysis. Patients were subsequently assigned to five groups according to the period of metastatic diagnosis. Results: It is shown that age at initial diagnosis, hormonal receptor status and site of metastasis are the most relevant prognostic factors for predicting survival from the time of metastastic occurrence. It is also shown that a metastasis-free interval is an easily and immediately available multifactorial prognostic index reflecting the multiparametric variability of the disease. Conclusion: These fundamental observations may assist physicians in evaluating the survival potential of patients and in directing them toward the appropriate therapeutic decision.

Among all the accelerated and partial breast irradiation (APBI) techniques, low then high dose rate, interstitial brachytherapy (HDIB) was the first to be used in this field. This study presents the preliminary clinical and dosimetric results of the APBI using HDIB, performed in Antoine Lacassagne Cancer Center of Nice.From June 2004 to March 2008, 61 patients (37 primary tumors and 24 second conservative treatments after local recurrence) presenting with T1-2 pN0 non-lobular invasive breast carcinoma, underwent lumpectomy with sentinel lymph node dissection and intraoperative tube placement for HDIB. Dose distribution analysis, using dose-volume histograms, was achieved based on a postoperative CT scan. A comparative dosimetric study was performed between optimized (O) and non-optimized (NO) dose distribution. Then, based on conformal index calculation, a novel index was proposed taking into account not only the conformity but also the homogeneity of HDIB implant. An analysis of dose gradient impact on HDIB biological equivalence dose was also conducted. Statistical analysis used T test confirmed by Wilcoxon test for cohort including less than 30 patients.The comparative dosimetric analysis between O and NO dose distributions shown that conformity indexes (conformal index, conformal number, and D90%) were significantly increased after optimization. Improving conformity leads to increasing hyperdosage volumes (V150% and V200%). A new index named conformity and homogeneity index (CHI) including V150% values, modified the conformal index. A total dose of 34 Gy, delivered through HDIB in 10 fractions over five days was biologically equivalent to 41.93 Gy assuming alpha/beta = 4 Gy and 75.76 Gy if the dose gradient was considered in the calculation.HDIB is considered as one of the best IPAS technique. HDIB allows dose distribution optimization, skin spearing and accurate clinical target volume definition. Furthermore, HDIB dose gradient could play a key role for breast cancer local control.

L’amelioration des techniques de prelevements associee a la standardisation des indications conduit a l’optimisation de la prise en charge diagnostique et pretherapeutique des lesions mammaires. De vastes etudes multicentriques successives americaines et allemandes, concernant des milliers de prelevements tant en microbiopsies qu’en macrobiopsies assistees par le vide, permettent de situer precisement la place de ces techniques dans le cadre d’une demarche de qualite en aval du depistage organise (1, 2). Neanmoins, les microbiopsies comme les macrobiopsies presentent des limites dont nous analyserons a travers les donnees de la litterature les causes et les consequences.

Le traitement conservateur (TC) repose sur une chirurgie d’exerese glandulaire permettant une exerese totale de la tumeur, laissant un sein d’aspect normal et un risque de recidive locale faible, sans qu’il y ait un sur-risque de metastase par rapport a une mastectomie. Dans la quasi-totalite des cas, le TC repose sur une association radiochirurgicale.

A new cell line (CAL51) was isolated from a malignant pleural effusion of a woman with metastatic breast cancer. These cells grow in continuous culture and exhibit the morphological, ultrastructural and immunohistochemical features of epithelial cells of mammary origin. They are tumorigenic in nude mice and clone in soft agar. Oestrogen receptors are not detected. CAL51 consists of a homogeneous population of cells with normal chromosomes even after the use of high resolution banding. Cytogenetic analysis of the cells from the tumour induced by CAL51 in the nude mouse confirmed the normality and the stability of the karyotype. All breast cancer cell lines established to date present abnormal karyotypes; CAL51 cell line may be more informative than cell lines with aberrant karyotypes for investigating essential genetic differences between normal and malignant mammary gland cells. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 Figure 7

Hypoxia stabilizes HIF-1alpha (Hypoxia Inducible Factor-1alpha), which then triggers the expression of several genes involved in many aspects of cancer progression, including metabolic adaptation, cell survival and angiogenesis. The aim of our study was to evaluate the impact of HIF-1alpha and CA IX (carbonic anhydrase IX) (one of its target genes) expression on prognosis and treatment outcome of patients with breast cancer. Because of the extreme O2-dependent instability of the protein, we first validated HIF-1alpha staining using xenograft tumours that were subjected to experimental conditions mimicking surgical clamping or sitting at room temperature under normoxic conditions after surgical excision but before fixation. Afterwards, the immunohistochemical staining of HIF-1alpha and CA IX was evaluated in 132 invasive breast carcinomas with a 10-year follow-up, and correlated to classical clinicopathological parameters and response to adjuvant therapy. No significant correlation was found between tumour size or nodal status and the expression of HIF-1alpha or CA IX. Statistically significant association was found between HIF-1alpha or CA IX staining and the grade, hormonal receptors loss and the presence of carcinoma in situ. Overexpression of HIF-1alpha and CA IX correlates with a poor prognosis in breast cancer. We show that HIF-1alpha is an independent prognostic factor for distant metastasis-free survival and disease-free survival in multivariate analysis. Furthermore, overexpression of HIF-1alpha or CA IX correlates with a poor outcome after conventional adjuvant therapy. CA IX is, however, a weaker prognostic and predictive factor than HIF-1alpha, and its association with HIF-1alpha does not modify the survival curve neither response to therapy, compared to HIF-1alpha alone.

Objectives: To investigate whether some aspects of patient or tumor characteristics influence the timing of local recurrence (LR) in breast cancer treated conservatively, and to assess the impact of the timing of LR on patient outcome. Methods: A retrospective analysis was conducted on patients treated with conservative breast surgery followed by radiotherapy for breast carcinoma who developed LR. Out of 2,008 cases treated in our Institute between 1977 and 2002, 180 ipsilateral LR were observed. Of these, 46 LR were observed within 36 months after treatment, called early local recurrence (ELR), 44 developed between 37 and 60 months, called medium local recurrence (MLR), and 90 occurred after 60 months, called late local recurrence (LLR). Patient and tumor characteristics were analyzed in the 2 groups and compared. Results: Primary tumors >20 mm were more frequently found in patients with ELR (31%) than in patients with LLR (17%, p = 0.047). Grade 3 tumors were more often encountered in patients with ELR than in patients with LLR (27 versus 7%, p = 0.0002). Patients with ELR more frequently had tumors with negative estrogen receptors than patients with LLR (37% versus 6%, p < 0.0001). There was no statistically significant difference in the axillary lymph node (LN) status between patients with ELR and those with LLR (35 and 23% of positive LN, respectively, p = 0.24). Tumor size, grade, LN status, hormone receptors and the timing of LR affected the specific survival (SS) from initial surgery. On multivariate analysis, only LN status and the timing of LR retained an independent prognostic value, with an odds ratio of 6.7 for ELR. After LR, the SS was also influenced by all of the above factors, and on multivariate analysis, LN status, hormone receptors and the timing of LR were independent predictors with an odds ratio of SS of 2.50 in case of ELR (p = 0.006). The 5-year SS after LR for ELR, MLR and LLR were 55.8, 74.8 and 79.5%, respectively. Conclusions: Unfavorable tumor characteristics such as big size, high grade, lack of hormone receptors, but not LN status, were associated with ELR. These findings suggest that patients with such aggressive tumor characteristics who do not recur early will have a lower risk of LLR than patients with more favorable factors.

Depuis 25 ans, la prise en charge des cancers du sein en situation adjuvante et metastatique s’est modifiee de maniere importante avec l’apparition de nouvelles therapeutiques en hormonotherapie, en chimiotherapie et en therapeutique ciblee. L’objectif de cette etude est d’evaluer les facteurs pronostiques classiques influencant la decision therapeutique et la survie en situation metastatique. D’autre part, cette etude epidemiologique a pour but d’evaluer l’evolution de la survie des patientes liees aux modifications therapeutiques mises en place depuis 25 ans.

modifications, dont les plus importantes concernent le statut ganglionnaire, impliquant un reclassement des tumeurs : – le nombre de ganglions envahis est pris en compte ; – les nodules tumoraux dans la graisse axillaire en dehors de tout aspect ganglionnaire residuel sont classee en ganglions metastatiques ; – le ganglion sentinelle est reconnu avec definition de la taille des metastases et de la methode pour les mettre en evidence (standard, immuno-histochimie, RTPCR) (1). Dans ce reclassement, ont ete integrees les propositions de P. Hermanek (40) : – les micro-metastases qui jusqu’alors avaient une taille inferieure ou egale a 2 mm sont classees PN1mi et mesurent de 0,2 a 2 mm de grand axe ; – les cellules tumorales isolees (CTI) sont definies comme seules ou groupees en petits amas de cellules inferieures a 0,2 mm de grand axe, identifiees par immunohistochimie ou RT-PCR. Elles sont classees PN0(i+) ou PN0(mol+). Elles ne doivent pas montrer de signes evidents d'agressivite (proliferation, stroma reaction) ; – les macro-metastases ont une taille superieure a 2 mm. Comment classer un ganglion comportant plusieurs foyers de CTI ou de micrometastases ? Il est seulement precise que si plusieurs ganglions sont le siege de micro-metastases, le stade passe a pN2 si au moins un ganglion presente une metastase superieure a 2 mm. Csemi (79) avec l’EWGBSP (Europe Working Group for Breast Screening Pathology) souligne l’impossible reproductibilite dans la detection entre CTI et micrometastases et le biais que cela genere dans les etudes. L'ambiguite dans l'abondante litterature consacree au ganglion sentinelle et aux etudes retrospectives reside dans le terme de metastases « occultes ». Il ne repond pas a une definition univoque seulement liee a la taille des metastases (2). Il peut s’agir, certes, de micro-metastases, mais D. L. Weaver les definit comme des metastases qui ont ete « ratees » lors du premier examen standard et qui peuvent etre identifiees ulterieurement par des moyens complementaires (relecture de lames, Le traitement de l’aisselle. Prise en charge des ganglions axillaires par le pathologiste

The aim of this work was to report on the clinical, radiological and histological characteristics of ameloblastomas concerning bone structures of the face, rare but not exceptional tumours, and to communicate our experience of their treatment.The authors reexamined six recent cases of patients presenting with ameloblastoma at the centre Antoine Lacassagne in Nice. The diagnostic context, the treatment and the development of the disease are given in detail, emphasizing the frequency of local relapse of this histologically benign condition.The study of these cases confirmed the benefit of surgical treatment of ameloblastoma. The frequency of local relapse in the cases of close resection, leaving in place micro-foci, justifies enlarged intervention, which is often bone destructive.When the continuity of the bone is interrupted, in particular at the level of the mandible, and if the general condition of the patient permits, repair is preferable. In this situation, the procedure of choice is micro-anastomosis of the fibula.

The development of imaging-guided biopsy techniques has considerably improved the early diagnosis of breast cancers following initial detection by screening. Nevertheless, in a small percentage of cases, histopathologic findings are unsatisfactory owing to false negative errors attributable to operator inexperience or inadequate sample material (this is especially true for microcalcifications with 20% underestimation rates for atypical hyperplasia); repeat biopsy is warranted in such situations. When a discrepancy exists with imaging findings and for cases of atypical epithelial hyperplasia, surgical excision is imperative so as not to overlook or underestimate a malignant lesion. Controversy continues concerning the best approach for radial scars (sclerosing ductal lesions), papillary lesions, atypical lobular hyperplasia and lobular carcinoma in situ: determination of which benign anomalies can merely be followed-up remains a problem. Better awareness of the limitations of percutaneous tissue sampling procedures should lead to refinement of the indications for these techniques and improvement of patient selection and thereby reduce delays in accurate diagnosis.

Disease staging of patients with breast cancer is based on the probability of metastatic disease, the reliability of complementary examinations, and therapeutic possibilities, evaluated on a cost/benefit basis. For regional disease staging, nodal status can be assessed by ultrasound, and the value of this approach can be optimized by imaging-guided biopsies. Ultrasound examination of nodes upstream of the sentinel node allows determination of the utility of this node and the indications for axillary resection. Work-up of metastatic spread is performed only after evaluation of risk factors for metastasis. Prior to therapy, and in the absence of any clinical warning signs for resectable tumors, there are no indications for imaging, which is reserved solely for locally advanced tumors.

Background and purpose To evaluate early and late reactions, local control, disease-free survival, cause-specific survival, and overall survival of elderly breast cancer patients treated with definitive once-a-week hypofractionated radiotherapy together with hormonal therapy. Patients and methods Between 1987 and 1999, 115 patients with a median age of 83 presenting with 124 non-metastatic breast carcinoma were treated with definitive once weekly hypofractionated radiotherapy associated with hormonal therapy. The main reasons for adopting this schedule were patient refusal of surgery, very old age, locally advanced case, and/or comorbid disease. Radiation was delivered as once-a-week, 6.5 Gy for a total breast dose of 32.5 Gy in five fractions, followed with 1–3 fractions of 6.5 Gy to the tumour site. The median follow-up was 41 months. Results Neoadjuvant hormonal therapy led to 56% reduction of the tumour volume. Late reactions occurred in 46 patients; they were mild to moderate in 87% of these patients. The Kaplan–Meier rate was 52% of patients, with 6% experiencing grade 3 reactions. The 5-year local progression-free rate was 78%. The corresponding cause-specific survival was 71%, and was influenced by T classification, nodal status, oestrogen receptors and the total dose. The first three factors retained an independent prognostic impact on multivariate analysis. The 5-year overall survival was 38%. It was affected by the T classification, lymph node involvement and the performance status (PS). Using a multivariate analysis, only T classification and PS were identified as independent factors regarding overall survival. Conclusions Definitive hypofractionated radiotherapy allows a good local control, with acceptable toxicity. This schedule associated with hormonal therapy is a good alternative to surgery in non-operable old patients and in case of patient refusal to surgery and to standard fractionation.

The HER2 proto-oncogene encodes a transmembrane protein, which is considered to function as a growth factor receptor. Overexpression of this protein found by immunohistochemistry in about 20% of infiltrating breast carcinomas, has a predictive value of response to treatment by trastuzumab, an anti-HER2 humanized monoclonal antibody. Search for HER2 gene amplification is necessary to adapt the immunohistochemical technique quality and also in the cases of delicate analysis or weak overexpression. It is usually carried out by Fluorescence In Situ Hybridization (FISH). A more recent hybridization technique, named CISH because of its chromogenic revelation is an alternative method, which gives highly correlated results with FISH. We present details of this technique, which may be more familiar for the pathologists than FISH, because reading analysis is similar to that of immunohistochemical staining.

The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers. and specialists from French public universities,general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients.To update clinical practice guidelines for the management of patients with salivary gland malignant tumors previously validated in 1997. These recommendations cover diagnosis, treatment and follow-up of patients with these tumors.The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been defined, the document is submitted for review by independent reviewers.This article presents the updated clinical practice guidelines concerning irradiation of patient with salivary gland tumors. The main recommendations are: 3 dimensional conformal radiotherapy (with or without intensity modulation) or 2D irradiation can be used; for surgical complete resected patients, postoperative photon radiotherapy should not be used in case of low grade stage I and 11 tumors(standard, level of evidence B2) but should be used for high grade stage II, II and IV tumors and for low grade stage III and IV tumors(standard, level of evidence B2). Neutron therapy should not be used in all of these cases (standard, level of evidence D); for patients presenting an incomplete macroscopic or microscopic surgical residual disease, postoperative irradiation must be delivered(standard). Neutron or photon therapy can be either delivered (options); for non operable patients neutron or photon therapy can be either delivered (options, level of evidence B2); for unresectable tumors or in case of recurrent neoplasms, exclusive neutron therapy or surgical tumor reduction combined with postoperative photon beam irradiation can be proposed (options, level of evidence C).

Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors.From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21-day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (750 mg/m2/day at 1st course; 430 mg/m2/day at 2nd and 3rd courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy.Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 2 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall survival were the Karnofsky index (71% survival at 3 years for patients with a Karnofsky index of 90-100% versus 30% for patients with a Karnofsky index of 80% versus 0% for patients with a Karnofsky index of 60-70%, p = 0.0001) and tumor location (55% at 3 years for oropharynx versus 37% for panpharynx versus 28% for hypopharynx, p = 0.009).These results confirm the efficacy of concomitant bid radiotherapy and chemotherapy in advanced unresectable tumor of the pharynx. The improvement in results will essentially depend on our capacity to restore in a good nutritional status the patients before beginning this heavy treatment.

Summary Purpose Because new therapeutic approaches target tumors expressing epidermal growth factor receptor (EGFR), the aim was to undertake a thorough analysis of the expression profile of EGFR in breast cancer and to reassess its prognostic value. Patients and methods Tumor EGFR levels were determined by a specific ligand binding assay in 780 consecutive breast cancer patients followed in our institute between 1980 and 1993. Mean age was 61 years (25–85 years). All patients had undergone tumor resection with axillary lymph node dissection: 373 patients (47.8%) underwent mastectomy, 37 (5%) subcutaneous mastectomy and 370 (47.2%) tumorectomy. Results EGFR levels ranged between non-detectable up to 789 fmol/mg protein. EGFR median value was 9 fmol/mg protein and only a small proportion of patients exhibited a relatively marked EGFR expression. There was no link between tumor size, grade, node status and EGFR tumoral levels. There was a constant and significant decrease in EGFR tumoral levels according to patient age. A significant inverse relationship was found between estradiol receptors (ER) and EGFR. Median follow-up was 97 months with a minimum at 4 months and a maximum at 228 months. From univariate analysis it was found that histological grade, tumor size, node status and ER status were all significant predictors of survival, considering metastasis-free as well as overall survival. Using multivariable analysis, only histological grade, tumor size and node status remained independent predictors of survival. Conclusions EGFR determination is of limited value as a prognostic indicator in breast cancer.