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1system were stored in which CTC were identified by an automated algorithm. Furthermore, this algorithm determined the Her-2 positivity threshold in each sample, using the fluorescence of leukocytes within each sample as internal control. Results: This automated Her-2 assessment method successfully distinguished Her-2 positive from Her-2 negative breast cancer cell lines. We report here for the first time that Her-2 expression of CTC varied greatly between but also within patients, suggesting a possible mechanism of treatment resistance. However, in M1 patients, a threshold of 75% of Her-2 positive CTC in patients with ≥5 CTC showed a relatively low discrepancy rate between the primary tumor and CTC Her-2 status. Applying this threshold, ∼2% of M1 patients with Her-2 negative primary tumors had Her-2 positive CTC status and ∼30% of M1 patients with Her-2 positive primary tumors had Her-2 negative CTC status. Interestingly, no Her-2 discrepancy was observed between CTC and primary tumors in M0 patients. Conclusions: Our results suggest that Her-2 status shift appears mostly at metastatic relapse, and consists generally in Her-2 low expression on CTC isolated from M1 patients with Her-2 positive primary tumors. These findings also demonstrate the feasibility of real-time quantitative and reproducible assessment of treatment targets on CTC, opening a path towards personalized treatment. Disclosure: All authors have declared no conflicts of interest.

557 Background: Trials have shown benefit of adjuvant trastuzumab (TZM) for N+ or supra-centrimetric HER2+ breast carcinomas. Methods: Retrospective multicenter series from 2000 to 2008 of infra-ce...

573 Background: Breast Cancer Index (BCI), a gene expression assay combining HoxB13/IL17BR ratio and Molecular Grade Index (MGI), is prognostic for the risk of distant recurrence and overall surviv...

1096 Background: Synchronous distant metastases (SDM) at diagnosis of breast cancer account for 5% of cases in ancient series. It is unclear what the recent prevalence of this condition is and whet...

1030 Background: The adjuvant chemotherapy +/− endocrine survival (ACES) predictor is a microarray-based genomic algorithm that combines signatures for sensitivity to endocrine therapy (SET), chemo-resistance, and chemo-sensitivity to provide a binary prediction of sensitivity or insensitivity to adjuvant chemotherapy +/− endocrine therapy (Symmans et al, SABCS, 2010). Methods:Eligible patients received ≥ 5 cycles of sequential anthracyline-taxane chemotherapy for HER2-negative cancer diagnosed ≥ 3 years ago. Sites sent de-identified frozen primary tumor samples to MDACC for gene expression profiling (Affymetrix U133A) for predictions of ACES, pCR (DLDA30), genomic grade (GGI), and intrinsic subtype (PAM50). Clinical information (from sites) and prediction results (from MDACC) were matched and analyzed at Georgetown. Distant relapse-free survival at 3 years (3yr-DRFS), and absolute risk reduction (ARR), for patients predicted to be treatment (Rx)-sensitive (versus Rx-insensitive) were evaluated with 95% c...

Background: The Cyfra 21-1 epitope is a polypeptide originating from cytokeratin-19 fragments possibly released by cell death and was an interesting serum marker in small and/or retrospective studies in breast cancer. On the back of circulating tumor cell (CTC) detection, the prospective IC 2006-04 study planned serum markers (CEA, Ca15.3, Cyfra 21-1) measurements. Methods: Metastatic breast cancer patients were included in a multicentric non-interventional study before the start of the 1st line chemotherapy. Blood biomarkers, including CTC detection (CellSearch®, ≥5CTC/7.5ml), were analyzed at 4 different times: before the start of the chemotherapy, before cycle 2 (ie mostly at day 21), at first tumor evaluation (ie before cycle 3/4) and at tumor progression. Results: 191 of the 267 patients included had Cyfra 21-1 assessed at inclusion. CTC level was ≥5CTC/7.5ml in 44% of the cases. Cyfra 21-1>ULNV (in 65% of pts) was not correlated with tumor ER/PR/HER2 status but strongly correlated with PS (p=8e-04), number of metastatic sites (p=0.0001), Ca15.3 (p=0.009), CEA (p=0.005), LDH (p=7e-08) and CTC detection (p=2e-06). CTC (≥5CTC/7.5ml) and Cyfra21-1 (>ULNV) correlation (N patients) The effectiveness of curcumin in the treatment of HER-2 overexpressed breast cancer was further confirmed through in vivo BT-474 xenograft model. The comparable ability of curcumin to inhibit cell proliferation, mobility, and angiogenesis as herceptin, combined with the potential ability to overcome the herceptin resistance, curcumin may be a novel agent in the treatment of HER-2 overexressed breast cancer. Logistic regression showed that LDH (p=0.0005) and CTC (p=0.0004) were the two independent predictors of Cyfra 21-1 elevation. Baseline Cyfra 21-1 >ULNV was associated with early tumor progression (RECIST, p=0.03). In multivariate analysis including standard biomarkers (without CTC), baseline Cyfra 21-1 was independently associated with PFS (p=0.008, RR), together with PS (P Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-01-01.

Background: Circulating tumor cells (CTCs) in peripheral blood and decrease during treatment has been reported as an independent prognostic factor in metastatic breast cancer (MBC) (Cristofanilli M., NEJM 2004). Data comparing CTC with circulating tumor markers are limited. We conducted a multicenter prospective study to validate these markers in a large series of patients receiving specifically first line chemotherapy (CT) for MBC including assessment of CA15.3, CEA and LDH. Methods: CTC were measured in 7.5ml of whole blood at baseline, before cycle 2, at clinical and/or radiological evaluation (C3-C4) and at tumor progression. Analysis was performed using the CellSearch™ System, combining EpCAM immunomagnetic selection (IMS) followed by anti-cytokeratin (A45B/B3). Double labeling for HER2 was performed in a subgroup of patients. Tumor markers were assessed locally with ELISA kit and high if above normal. Results: From 06/07 to 9/09, 267 patients with measurable or evaluable disease starting first line CT for MBC were included in five French Cancer Centers. Median follow-up was 16 months, 57 deaths and 160 progressions were observed. Median age was 57 years, 39 patients (15%) had HER2+ tumor and received trastuzumab, 55 (21%) had triple negative tumor, 125 received bevacizumab associated with CT, 260 were evaluable for CTC levels at baseline, 170 (65%) had ≥1CTC and 115 (44%) ≥5CTC. CTC HER2 status was assessed in 113 patients at baseline and was positive in 64% of the cases in at least one cell. CA15.3 was high in159/247 (64%), CEA in 109/212 (51%) and LDH in 99/220 (45%). CTC were highly correlated with tumor markers, tumor burden, performans status (PS), number of metastatic sites, liver metastasis) but were independent of tumor biology (HER2 status, Triple Negative BC (TNBC), grade). At first evaluation (C3-C4), 110/225 patients (49%) had objective response. At univariate analysis, high CTC level with a threshold of 1 or 5 at base line, before C2 (3-4w) and at radiological evaluation (C3-C4, 9-12w) was predictive of poor progression-free survival (PFS) and overall survival (OS) (p Conclusions: This is the largest prospective series validating the prognostic value of CTC in first line chemotherapy MBC independently from serum tumor marker for PFS and OS. Persistence of a high level of CTC before second cycle of chemotherapy is a strong and early predictive marker of poor PFS, before radiological evaluation. A prospective multicenter randomized trial (CIRCE01) to assess the use of CTC to modify treatment after second line chemotherapy is ongoing. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S6-6.

Background: Fine-needle aspiration cytology (FNAC) has been used extensively in the diagnosis of breast lesions, but false-negative rates are a matter of concern. Immediate onsite evaluation of breast lesions, combining FNAC results with clinical and radiological data allows improving its diagnostic accuracy. The objective of this study was to evaluate the diagnostic accuracy of a large series of FNAC of breast lesions during the first 3-year period of a dedicated one-stop clinic, by comparing the FNAC results with the corresponding definitive histological examination outcome or the results of the radiological follow-up at 18 months. Method: Data of all consecutive patients (pts) whose lesions were prospectively characterized by ultrasonography (US) and diagnosed by FNAC in the one stop clinic of the Institute Gustave Roussy between May 2004 and March 2007. Histological verification by core-needle biopsy or surgery was systematically performed for lesions classified malignant or suspicious by cytopathology, and for benign lesions, when no perfect concordance between clinico-radiologic features and FNAC results (such as benign FNAC but BI-RAD 5) was found. For non-operated patients, follow-up consisted on biannual US and/or mammography; the results at 18 months were considered. Pts characteristics, radiological findings, cytopathological and histological results were extracted from the hospital computerized prospectively registered medical records. Complete sensitivity (number of carcinomas that were malignant or suspicious by cytopathology) and full specificity (benign lesions at cytology of the total number of benign lesions) were calculated by comparing the cytopathological results to the histological or the long-term follow-up status. Results: A total of 1822 nodular breast lesions (mean size: 20 mm, BI-RAD ACR 1/2/3/4/5/unknown: 10/96/471/459/777/9) in 1739 pts (mean age: 56 years) were studied. FNAC was US-guided in 1115 lesions (61 %). Lesions were classified by FNAC as malignant in 842 (46%), benign in 771 (42%), suspicious in 154 (9%), and unsatisfactory in 55 (3%) cases. Complete sensitivity (number of carcinomas that were malignant or suspicious by cytopathology) was estimated at 98.5%, whereas full specificity (benign lesions at cytology of the total number of benign lesions) was equal to 94.4%. There were 4 false-positive lesions and 32 false-negative lesions, but all these lesions except one were operated as radiological results were suspicious of malignity. Conclusions: Breast FNAC performed in a dedicated one-stop clinic with immediate on-site diagnosis presented a low rate of unsatisfactory specimens and a very efficient tool for triaging patients candidates for histological evaluation conversely for follow-up by imaging. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-05.

638 Background: IBC is the most aggressive form of locally advanced breast cancer with a poor clinical outcome. The locoregional treatment is crucial because local relapses are commonly associated ...

10589 Background: Circadian clock involves 15 specific genes which control cell cycle, apoptosis, DNA repair and metabolism (Levi et al. ARPT,2010). Circadian disruption is associated both with an ...

Background:FGFR1 is a tyrosine kinase receptor involved in cell proliferation, migration and differentiation. FGFR1 gene is amplified in about 10% of breast cancer. Several studies have previously reported that FGFR1 inhibition could lead to a decrease in cell proliferation. Recent data obtained in prostate cancer have shown that FGFR1 activation could mediate epithelial to mesenchymal transition. In the present study, we evaluated the rational to target FGFR1 in clinical setting.Material and methods:We first assessed whether FGFR1 amplification was associated with a specific breast cancer phenotype. We assessed FGFR1 amplification by CGH array on 235 samples and by FISH (Z-2072, Spec FGFR1/Cen8 dual color probe, Zytovision®) on 260 samples, not included in the CGH part. We then assessed the functional effects of FGFR1 inhibitions in vitro. The antiproliferative effect of E3810 (FGFR1 inhibitor) was assessed both on FGFR1-non amplified (T47D/MCF7) and FGFR1 amplified (SUM44PE/MDA134) cell lines. Effect of FGFR1 inhibition was assessed on gene expression profiling.Results:When assessed by FISH, FGFR1 amplification was observed in 23/260 cases. Most of the samples (62%) exhibited an ER+/PR- phenotype, suggesting activation of intracellular kinase. FGFR1 amplification was observed in 24 out of 235 samples (10%). Interestingly, FGFR1 amplification was associated with gene gain in FGF3/FGF4/FGF19 (11q13) (55% versus 22%, p=0.05). FGFR1 inhibition by E-3810 inhibits MAPk phosphorylation, cell proliferation. A differential IC 50 for cell proliferation was observed between amplified cell lines and control cell lines. Preliminary data on gene expression profiling suggest that FGFR1 inhibition on breast cancer cells could lead to significant decrease in the Sox9 expression, a protein involved in epithelial to mesenchymal transition.Conclusion:FGFR1-amplified breast cancers present a discrete phenotype, including a high rate of ER+/PR- and high rate of FGF3/4/19 gains. Pharmacologic inhibition of FGFR1 leads to cell proliferation decrease and modulation of genes involved in EMT. These data suggest that there is a rational to target FGFR1 in clinical setting in patients with FGFR1-amplified breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4170.

Objectifs Analyse des biopsies guidees par IRM de lesions suspectes en IRM mammaire chez les femmes a risque de cancer du sein : experience de l’IGR. Materiels et methodes Revue des dossiers de 83 patientes a risque de cancer du sein ayant beneficie d’une macrobiopsie guidee par IRM (systemes VACORA (BARD ® ) et EnCor (Senorx ® ) pour une lesion suspecte du sein seulement visible en IRM. Le type de rehaussement, la technique, le temps d’examen, la correlation anatomopathologique finale pour les patientes operees et la survenue de complications eventuelles ont ete analyses. Resultats Quatre vingt trois biopsies ont ete realisees chez 83 patientes dont 24% etaient mutees BRCA (21/83). Trente six masses et 47 non-masses etaient biopsiees. Trente deux lesions etaient malignes (32/83, 39%) et 61 benignes (61/83, 61%) incluant 9 cas de lesions frontieres (9/61, 15%). Vingt huit correlations etaient possibles avec l’anatomopathologie definitive : aucune lesion maligne sur la biopsie n’a ete reclassee benigne ; dans 4 cas (4/28, 25%), le type histologique a ete modifie. Trois faux negatifs (1 erreur de ciblage, 2 sous-estimations) ont ete diagnostiques apres surveillance rapprochee. Conclusion La biopsie guidee par IRM est un examen indispensable a la prise en charge des femmes a risque de cancer du sein, mais doit etre maitrisee et evaluee.

615 Background: International guidelines recommend rapid diagnostic and therapeutic procedures for suspect breast lesions. However, the impact of the interval between screening and treatment (trt) (STI) on the severity of the disease remains unclear. We explored the potential impact of STI on a surrogate of survival, axillary nodal involvement (N+), among 1,000 recently diagnosed BC pts, as well as the causes of potential delays. Methods: We collected complete data of prospectively recorded community BC cases in a single regional cancer center between January 1, 2005, and October 10, 2007. Pts were eligible if they i. had a final diagnosis of invasive BC ii. were operated as first trt for BC, iii. had no history of other previous malignancy within the past 5 year period. Logistic regression analyses (SAS) were used to determine factors predictive of N+ and those influencing intervals between first description of the lesion and first therapeutic surgery (STI). Candidate factors included socio-economic variables (marital status, occupation, county of living, country of birth), personal and familial medical history parameters, as well as BC characteristics. Results: 990 pts met the inclusion criteria and had full data available. Med age: 59 years, BI-RAD ACR3/4/5: 2/41/55%, med pathological tumor size (pT): 16 mm (2–100), N+: 41%, med delay between first description of the lesion and surgery: 67 days. Factors predicting longer STI were: Birad ACR No significant financial relationships to disclose.

Abstract #5004 Background: Several studies have highlighted the potential benefit of early breast cancer (BC) diagnosis through breast MRI for high risk patients (pts). However, MRI is an expensive test with a low positive predictive value and has not been proven to reduce mortality rates in women carrying BRCA1/2 deleterious gene mutations (mut). At Institut Gustave Roussy, we started intensive BC screening programs for BRCA1/2 carriers (annual MRI + mammogram + bi-annual US) in 2001. The aim of this study was to compare the characteristics and prognostic features of BC in BRCA1/2 pts diagnosed inside or outside screening programs. Patients and Methods: All female BRCA1/2 mut carriers who have been treated for a new BC in our institution between 2001 and 2008, were entered into this study. All BRCA1/2 mut testing have been performed under the French guidelines and recommendations. We compared the clinico-pathological data, treatments and prognostic features between group 1 (pts diagnosed while on an intensive dedicated screening program) and group 2 (pts diagnosed outside these programs). Pts characteristics were compared using student T-test, and survival curves using Log-Rank tests. Results: 122 pts met the inclusion criteria: 20 in group 1, 102 in group 2. > 95% of pts in group 2 were not aware of their BRCA1/2 mut at time of diagnosis. In group 1, 17 cancers were diagnosed primarily through MRI (85%), while 3 were self-detected interval BC. Pts in group 1 had tumors with significantly better prognostic factors and received less CT. 3-year DFS significantly differed between groups 1 (100%) and 2 (74% (IC: 64-81 (p=0.04). 3-years MFS was 100 and 80% (p= 0.08), 3-years OS was 100 and 94% (p=0.26) in groups 1 and 2. Conclusion: These early data strongly suggest an important benefit in terms of disease-free survival and treatment sparing for i. the knowledge of a BRCA1/2 mut; ii. inclusion into intensive BC screening programs including MRI. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5004.

Abstract #5001 Purpose: CEDM is a recent development of digital mammography using the intra-venous injection of an iodinated contrast agent in conjunction with a mammography examination. The objective of this paper is to present two techniques developed to perform CEDM examinations, the preliminary clinical experiences and potential clinical applications of this new breast imaging procedure. Material and methods: Between 2005 and 2008, 140 consenting women with suspicious findings on mammography and or ultrasonography underwent CEDM using modified full-field digital mammography systems (GE Healthcare, Chalfont St-Giles, UK). A temporal subtraction sequence with acquisition of high-energy images before and after contrast medium injection was used for the first 20 patients. A dual energy technique with acquisition of a pair of low and high-energy images only after contrast medium injection was used for the other 120 patients. Results: CEDM, either using temporal or dual energy technique, improved the probability of malignancy and the BIRADS assessment compared to conventional mammography alone. The temporal subtraction technique offered the possibility to analyze the kinetic curve of enhancement of breast lesions, similar to breast MRI. Dual energy technique did not provide information about the kinetic of tumor enhancement but allowed the acquisition of multiples views of the same breast or bilateral examination and was less sensitive to patient motion than temporal CEDM. The potential clinical applications are the determination of the extent of disease, the assessment of recurrent disease, the clarification of mammographically equivocal lesions, the detection of occult lesions on standard mammography, particularly in dense breast, and the monitoring of the response to chemotherapy. Conclusion: Initial clinical experience has shown the ability of CEDM to map the distribution of neovasculature induced by cancer using mammography. CEDM should result in a simple way to enhance the detection and the characterization of breast lesions and to provide some prognostic factors of breast carcinomas. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5001.

Abstract #6063 Background: p27 is a cyclin-dependent kinase (cdk) inhibitor that plays a role in cell cycle regulation. The expression of this protein, assessed by immunohistochemistry (IHC), has prognostic value for overall survival in breast cancer patients (Porter P.L., J Natl Cancer Inst., 2007). Based on this, we hypothesized that p27 could be a predictive factor for the efficacy of adjuvant anthracycline (A)-based chemotherapy in early breast cancer. Methods: Tumor samples from 823 patients, included at Institut Gustave Roussy (IGR) in two randomized trials comparing an A-based chemotherapy with no adjuvant treatment, were used to construct a tissue microarray. We previously reported predictive values of ER, Her2 expression and molecular subclassification using the same tissue array (Conforti R., Ann Oncol., 2007). Nuclear and cytoplasmic expression of p27 was assessed by the AQUA system. A p27 ratio of nuclear and cytoplasmic expression (p27 N/C ratio) was calculated for each tumor sample. The prognostic and predictive value of the continuous value of p27 N/C ratio was assessed by a Cox regression model adjusted for treatment, age, tumor grade, stage and ER expression (IHC) and stratified by trial. Results: p27 was assessable in 715 primary tumors. The p27 N/C ratio was significantly different according to the molecular subclasses (p=0.001) and was higher in Her2- versus Her2+ and in EGFR+ versus EGFR- tumors (p=0.0075 and p Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6063.

Objectifs Comparer les resultats d’une analyse par systeme CAD IRM a celle du radiologue pour des lesions suspectes en IRM. Materiels et methodes Vingt-trois lesions mammaires classees BIRADS 3,4 ou 5 en IRM, biopsiees chez des femmes a risque, ont ete retrospectivement analysees avec un systeme CAD IRM. Les caracteristiques IRM des lesions, analysees par deux radiologues avec le score de Teifke, (incluant les parametres du lexique BIRADS) sont comparees au score du CAD, et correlees a l’histologie. Resultats Vingt-trois lesions ont ete incluses : 9 benignes, 7 frontieres, 7 malignes (3 CIS, 4 CCI). Le score moyen IRM etait de 3 avec CAD versus 4 pour le radiologue seul (lesions benignes), de 3 versus 4 (lesions frontieres) et de 3 versus 4 (lesions malignes). Le taux de faux negatifs du CAD etait de 66 % alors que le taux de faux positifs du CAD etait diminue par rapport a l’analyse du radiologue (44 % versus 69 %). Conclusion Le taux eleve de faux negatifs doit inciter a la prudence pour l’utilisation des CAD IRM, meme s’ils peuvent aider a diminuer le nombre de faux positifs. Ce probleme peut etre lie a une importance predominante de l’analyse cinetique surtout dans les intracanalaires.

Objectifs Determiner des facteurs predictifs de malignite des foyers de microcalcifications mammaires en fonction des parametres cliniques, histologiques et radiologiques. Materiels et methodes Entre 2003 et 2005, 520 foyers de microcalcifications BIRADS 3 a 5 ont ete biopsies (11G) puis operes si un diagnostic de malignite ou d’hyperplasie canalaire atypique (HEA) etait porte (n = 230) ou dans les cas de discordance radio-clinique. Les facteurs predictifs potentiels de malignite testes comportaient des parametres radiologiques (aspect, taille, evolutivite du foyer) et cliniques (âge, Gail, THS). L’analyse statistique a ete faite par regression logistique conditionnelle. Resultats Soixante-seize pour cent (N = 75) des foyers BIRADS 5 (N = 98) et operes etaient malins avec 4 cancers additionnels sur 7 lesions dont la biopsie avait retrouve une HEA. Trente-deux pour cent (n = 126) des foyers BIRADS 4 (n = 384) etaient malins, avec un taux de 19 % de malignite parmi les HEA (n = 6/31). 6 foyers BIRADS 3 sur une population a risque (n = 38) etaient finalement malins. Parmi les facteurs etudies sur les BIRADS 4, seul le caractere evolutif du foyer etait significativement correle au risque de malignite (p = 0,01). Conclusion Il est essentiel de continuer a operer les cas d’HEA detectes par macrobiopsie. Le caractere evolutif du foyer reste le meilleur parametre predictif de malignite.

Resume Le depistage du cancer du sein chez les femmes genetiquement predisposees est un challenge de l’imagerie aujourd’hui. En effet, ces patientes ont 75 a 80 % de risque de developper un cancer du sein dans leur vie, la moitie survenant a moins de 40 ans, alors que la mammographie est plus difficilement interpretable. Le couple mammographie-echographie permet de depister seulement un cancer sur deux. Les etudes les plus recentes ont permis d’etablir que l’IRM est aujourd’hui le meilleur examen de depistage dans cette population et permet de depister 80 a 100 % des cancers. L’IRM doit etre annuelle et bilaterale. La prevalence de cancer en IRM de depistage des patientes mutees BRCA est de 2 a 7 %. La valeur predictive positive de la biopsie dans les etudes de depistage IRM des femmes a haut risque (18-88 %) est egalement significativement plus elevee que celle des etudes de depistage echographique (7-14 %). Cependant, le nombre de faux positifs ou de lesions BI-RADS 3 est frequent car les patientes sont jeunes, et l’analyse des images est souvent difficile. Les lesions suspectes en IRM doivent faire l’objet d’une echographie dirigee et en cas de negativite, etre biopsiees sous controle IRM ou TDM.

Objectifs La neoangiogenese est une caracteristique des lesions malignes du sein. Neanmoins l’etude des neovaisseaux par Doppler couleur est difficile du fait de leur faible densite et de leur basse vitesse de circulation. Le but de ce travail est de sensibiliser la detection de la neoangiogenese par l’injection de produit de contraste ultrasonore. Materiels et methodes Vingt trois lesions BIRADS 3, 4 et 5 ont ete examinees par echographie avant et apres injection de Sonovue ® , grâce a une nouvelle methode Doppler CPS Siemens ® . La cinetique et les caracteristiques de rehaussement ont ete analysees secondairement (Visilog, Noesis ® ) et confrontees a une etude histologique avec analyse de la densite vasculaire par immunohistochimie. Resultats Vingt lesions malignes et 3 lesions benignes etaient etudiees ; un rehaussement suspect (rapide, inferieur a 15 secondes) et intense etait visible dans 18 cas sur 20. Les deux faux negatifs correspondaient a des carcinomes canalaires de bas grade. Deux faux positifs (adenofibrome hypervasculaire et tumeur phyllode) avaient un rehaussement plus faible et retarde. Les resultats de l’echographie etaient valides par l’etude immunohistochimique. Conclusion L’etude de la neoangiogenese des lesions mammaires est facilitee par les nouvelles techniques de Doppler et les produits de contraste de seconde generation.

Objectifs pedagogiques Decrire un exemple de consultation multidisciplinaire de senologie. Discuter ce qu’attendent les medecins cliniciens senologues du radiologue en senologie. Discuter la place du radiologue en senologie, en particulier pour les implications cliniques et therapeutiques. Discuter la place de l’information a la patiente et jusqu’ou peut aller le radiologue en senologie. Resume La generalisation du depistage organise du cancer du sein est en partie a l’origine de l’augmentation de la detection des cancers du sein au stade infraclinique. Le diagnostic initial est essentiellement radiologique, mais implique aussi les acteurs essentiels, que sont l’oncologue medical, le chirurgien, l’anatomopathologiste ou le radiotherapeute. Les interactions entre le radiologue et ses confreres cliniciens sont nombreuses et se jouent au cours de plusieurs etapes, du diagnostic initial, au traitement ou a la surveillance post-therapeutique. Il est donc encore plus important, dans ce domaine, pour le radiologue senologue de s’impliquer dans la clinique et de connaitre les enjeux diagnostiques et les sequences therapeutiques. Cependant, il est egalement fondamental que les cliniciens et les radiologues cooperent ensemble pour la prise en charge optimale des patientes, que ce soit dans des centres specialises publics ou prives, ou egalement dans des reseaux ville-hopital. Le but de cet enseignement est de presenter un exemple de consultation multidisciplinaire en senologie et de definir les roles et les attentes des cliniciens et des radiologues pour la prise en charge optimale des patientes. En particulier, la place de l’information donnee a la patiente par le radiologue sera discutee.

Resume La neoangiogenese est une caracteristique reconnue des lesions malignes, en particulier des lesions mammaires. Or, l’echo-Doppler couleur dans le sein est difficile en raison de la lenteur des flux vasculaires et de la faible densite de la microvascularisation. Cependant, l’amelioration de la resolution du mode B et l’utilisation de sondes de tres haute frequence ont augmente la valeur diagnostique de l’echographie, notamment en facilitant la detection optimale des flux lents. La caracterisation des lesions tissulaires peut etre amelioree par l’utilisation de produits de contraste ultrasonores. Ceux-ci augmentent le signal vasculaire des petites arteres intra-tumorales et ameliorent la sensibilite du Doppler couleur. L’utilisation des agents de contraste de deuxieme generation semble tres prometteuse. Des logiciels dedies tracent des courbes de rehaussement, comme en IRM. La technique doit etre standardisee en fonction du type d’agent de contraste. Des informations utiles pour la differenciation des lesions benignes ou malignes sont obtenues en analysant les principaux parametres du rehaussement vasculaire (pente, intensite et precocite du pic maximal, duree du rehaussement, pente de lavage eventuel). Le rehaussement d’une lesion maligne est precoce (moins de 2 minutes) modere ou eleve, alors que le rehaussement des lesions benignes est faible ou nul.

International audience; Background: In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events.Methods: PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901.Findings: 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3-8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93-1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group.Interpretation: The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months.