Outcome in Advanced Ovarian Cancer following an Appropriate and Comprehensive Effort at Upfront Cytoreduction: A Twenty-Year Experience in a Single Cancer Institute

Objectives. The purpose of this retrospective evaluation of advanced-stage ovarian cancer patients was to compare outcome with published findings from other centers and to discuss future options for the management of advanced ovarian carcinoma patients. Methods. A retrospective series of 340 patients with a mean age of 58 years (range: 17–88) treated for FIGO stage III and IV ovarian cancer between January 1985 and January 2005 was reviewed. All patients had primary cytoreductive surgery, without extensive bowel, peritoneal, or systematic lymph node resection, thereby allowing initiation of chemotherapy without delay. Chemotherapy consisted of cisplatin-based chemotherapy in combination with alkylating agents before 2000, whereas carboplatin and paclitaxel regimes were generally used after 1999-2000. Overall survival and disease-free survival were analyzed by the Kaplan-Meier method and the log-rank test. Results. With a mean followup of 101 months (range: 5 to 203), 280 events (recurrence or death) were observed and 245 patients (72%) had died. The mortality and morbidity related to surgery were low. The main prognostic factor for overall survival was postoperative residual disease (P < .0002), while the main prognostic factor for disease-free survival was histological tumor type (P < .0007). Multivariate analysis identified three significant risk factors: optimal surgery (RR = 2.2 for suboptimal surgery), menopausal status (RR = 1.47 for postmenopausal women), and presence of a taxane in the chemotherapy combination (RR = 0.72). Conclusion. These results confirm that optimal surgery defined by an appropriate and comprehensive effort at upfront cytoreduction limits morbidity related to the surgical procedure and allows initiation of chemotherapy without any negative impact on survival. The impact of neoadjuvant chemotherapy to improve resectability while lowering the morbidity of the surgical procedure is discussed

A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer

<p>Abstract</p> <p>Background</p> <p>The distinction between primary and secondary ovarian tumors may be challenging for pathologists. The purpose of the present work was to develop genomic and transcriptomic tools to further refine the pathological diagnosis of ovarian tumors after a previous history of breast cancer.</p> <p>Methods</p> <p>Sixteen paired breast-ovary tumors from patients with a former diagnosis of breast cancer were collected. The genomic profiles of paired tumors were analyzed using the Affymetrix GeneChip^®Mapping 50 K Xba Array or Genome-Wide Human SNP Array 6.0 (for one pair), and the data were normalized with ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) algorithm or Partek Genomic Suite, respectively. The transcriptome of paired samples was analyzed using Affymetrix GeneChip^®Human Genome U133 Plus 2.0 Arrays, and the data were normalized with gc-Robust Multi-array Average (gcRMA) algorithm. A hierarchical clustering of these samples was performed, combined with a dataset of well-identified primary and secondary ovarian tumors.</p> <p>Results</p> <p>In 12 of the 16 paired tumors analyzed, the comparison of genomic profiles confirmed the pathological diagnosis of primary ovarian tumor (n = 5) or metastasis of breast cancer (n = 7). Among four cases with uncertain pathological diagnosis, genomic profiles were clearly distinct between the ovarian and breast tumors in two pairs, thus indicating primary ovarian carcinomas, and showed common patterns in the two others, indicating metastases from breast cancer. In all pairs, the result of the transcriptomic analysis was concordant with that of the genomic analysis.</p> <p>Conclusions</p> <p>In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors. Transcriptomic analysis may be used when primary breast tissue specimen is not available.</p

Facteurs de décision de non-reconstruction du sein chez 1937 patientes ayant eu une mastectomie pour cancer à l'Institut Curie

Objectif: Déterminer les facteurs de décision de non-reconstruction et évaluer la qualité de l'information chez les patientes ayant eu une mastectomie pour cancer du sein. Patientes et méthodes: Etude rétrospective (n=1937) : comparaison des facteurs clinico- biologiques des patientes mastectomisées reconstruites et non reconstruites. Questionnaire adressé à 10% des patientes non reconstruites (n= 132). Résultats: Taux de non reconstruction: 68 % . Facteurs associés à une non reconstruction (analyse multivariée, pI, absence de tabagisme actif, traitement par radiothérapie, surexpression de HER 2, état métastatique. La non reconstruction est un choix personnel dans 80 % des cas. Information jugée comme absente ou insuffisante dans 62 % des cas. Conclusion: Les causes de non reconstruction sont liées aux pronostics du cancer, au mode de vie des patientes et le plus souvent à un choix personnel.Purpose: To determinate clinico-biologic factors associated to no breast reconstruction after mastectomy for breast cancer and to evaluate information quality. Patients and methods: Retrospective study (n= 1937) : comparison of clinico-biologic factors of patients who had a reconstruction to them who didn't have. Analysis of a questionnaire sent to a 10 % of patients with no reconstruction (n= 132). Results: Rate of no (Çconstruction was 68%. Factors associated to no breast reconstruction (multivariate analysis, p l, absence of smoking, radiotherapy treatment, overexpression of HER2, metastatic status. No reconstruction is a personal choice in 80 %. Information considered as absent or deficient in 60% of the patients. Conclusion: Reasons of no reconstruction are linked to cancer prognostic, patient' s characteristics and ways of live but also to personal choice.PARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

Impact pronostic des atteintes lymphatiques minimes chez les patientes ayant un cancer du sein (à propos de 241 cas de micrométastases et cellules tumorales isolées dans le ganglion sentinelle avec curage axillaire négatif)

Objecif: le but de cette étude est de déterminer la survie sans récidive (SSR) des patientes avec un cancer du sein ayant une atteinte lymphatique minime (ALM) isolée au GS, soit pN0i+ et pN1mi. Patientes et méthodes: les patientes ayant eu un GS positif avec CA négatif entre Janvier 2000 et Décembre 2006 ainsi que celles ayant eu un GS négatif sans CA ont été sélectionnées. Les SSR ont été estimées selon la méthode de Kaplan-Meier et comparées par le test du Log-rank. Résultats: la population a été divisée en quatre groupes selon le statut ganglionnaire du GS, pN0i+ (n=107), pN1mi (n=134), pN1 (n=180) et pN0 (n=1460). Le suivi moyen a été de 52 mois. Les patientes ayant un GS avec ALM avait une SSR à 36 mois comparable aux patientes pN0, respectivement 100% pour pN0i+, 95.5% pour pN1mi, 98.9% pour pN1 et 96.8% pour pN0 (p=0.599). Conclusion: dans cette série, les patientes ayant une ALM isolée du GS n ont pas de diminution de la SSR comparées aux patientes ayant un GS négatif. Cependant un suivi à plus long terme est nécessaire pour confirmer ces résultats ainsi que l'impact des ALM sur la survie globale.Background: sentinel lymph node (SLN) biopsy has led to an increase in the detection of minimal lymph node involvement (micrometastases-pN1mi and isolated tumor cells-pN0i+). The outcome may be different between patients with minimal lymph node involvement (MLNI) in the SLN with negative complementary axillary dissection (CAD) and those with negative SLN. The aim of this study was to determine the disease free survival (DFS) of breast cancer patients with MLNI in SLNs. Patients and methods: the institute Curie SLN database was used to identify all patients who underwent a SLNB for invasive breast cancer between january 2000 and december 2006 and had MLNI with a negative CAD or negative SLN without CAD. DFS was estimated using Kaplan-Meier method. The log-rank test was used to determine differences in DFS of patients from different groups. Results: patients was divided into four groups according to axillary status, pN0i+ (n=134), pN1 (n=180) and pN0 (n=1460). The median follow-up was 52 months. There was no statistical difference in axillary recurrence rates between pN0i+, pN1mi, pN1 and pN0 respectively 0%, 0%, 0% and 0.1% at 36 months (p=0.753). MLNI in SLN was not associated with a significantly shorter DFS at 36 months, compared with negative SLN, respectively 100% for pN0i, 95.3% for pNmi, 98.8% for pN1 and 96.5% for pN0 (p=0.599). Conclusions: in this series, MLNI with negative CAD was not associated with a worse DFS compared to negative SLN. It seems therefore important to distinguish MLNI followed by a negative CAD, from MLNI without CAD performed. However, longer follow-up is needed to confirm these results, as well as impact of MLNI on overall survival.ST QUENTIN EN YVELINES-BU (782972101) / SudocSudocFranceF

Vingt ans de chirurgie des cancers épithéliaux de l'ovaire stades avancés (l'expérience de l'Institut Curie)

La chirurgie pragmatique dans le cancer épithélial de l ovaire à des stades avancés à l Institut Curie, comprend une chirurgie première de cytoréduction, excluant des exérèses digestives et/ou péritonéales étendues, et sans lymphadenectomie systématique. Cela permet une mise en route rapide de la chimiothérapie, dans un délai raisonnable. Dans cette étude rétrospective, nous avons étudié l effet de cette chirurgie dite pragmatique , sur la survie globale et la survie sans récidive. 340 patientes, de 58 ans d âge moyen (17 à 88 ans), présentant des stades III et IV de cancer épithélial de l ovaire, ont été prises en charge entre janvier 1985 et janvier 2005. Elles ont toutes été opérées puis ont, pour la plupart, reçu une chimiothérapie à base de platine, associée à des alkylants avant 1999, et associée à du paclitaxel après 1999. La survie globale et sans récidive ont été analysées avec la méthode de Kaplan Meier et le log-rank test. Après un suivi moyen de 101 mois, 280 événements ont été observés (récidives ou décès), et 245 patientes (72%) sont décédées. La mortalité et la morbidité liées à la chirurgie sont extrêmement faibles. Le principal facteur pronostic influant sur la survie globale est la taille du résidu post-opératoire (p<0,0002), en revanche pour la survie sans récidive, le type histologique de la tumeur semble plus important (p<0,0007).L analyse multivariée, fait quant à elle ressortir trois éléments : la chirurgie optimale, le statut ménopausique, et la présence de taxane dans la combinaison de la chimiothérapie. Ces résultats confirment que la chirurgie optimale dans les stades avancés de cancers épithéliaux de l ovaire influe sur la survie globale. Le concept de chirurgie pragmatique est une option dans la prise en charge des cancers épithéliaux de l ovaire.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

La détection de cellules immunomarquées, dans l'analyse du ganglion axillaire sentinelle (pNOi+), modifie-t-elle la prise en charge post-opératoire des patientes ayant un cancer du sein ?

REIMS-BU Santé (514542104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Time-Dependent Prognostic Impact of Circulating Tumor Cells Detection in Non-Metastatic Breast Cancer: 70-Month Analysis of the REMAGUS02 Study

Introduction. In non-metastatic breast cancer patients, the REMAGUS02 neoadjuvant study was the first to report a significant impact of circulating tumor cells (CTCs) detection by the CellSearch system on the distant metastasis-free survival (DMFS) and overall survival (OS) endpoints. However, these results were only reported after a short follow-up. Here, we present the updated data, with a longer follow-up. Material and Methods. CTC count was performed before and after neoadjuvant chemotherapy in 118 patients and correlated to survival. Results. CTC count results were available before and/or after neoadjuvant chemotherapy in 115 patients. After a median follow-up of 70 months, detection of ≥1 CTC/7.5 mL before chemotherapy (N=95) was significantly associated with DMFS (P=0.04) and OS (P=0.03), whereas postchemotherapy CTC detection (N=85) had no significant impact. In multivariable analysis, prechemotherapy CTC and triple negative phenotype were the two independent prognostic factors for survival. We observed that the CTC impact is most significant during the first three years of follow-up. Discussion. We confirm that the detection of CTC is independently associated with a significantly worse outcome, but mainly during the first 3-4 years of follow-up. No prognostic impact is seen in patients who are still relapse-free at this moment

Validation over time of a nomogram including HER2 status to predict the sentinel node positivity in early breast carcinoma.

International audienceBACKGROUND: The molecular subtypes of breast cancer have different axillary status. A nomogram including the interaction covariate between estrogen receptor (ER) and HER2 has been recently published (Reyal et al. PLOS One, May 2011) and allows to identify the patients with a high risk of positive sentinel lymph node (SLN). The purpose of our study was to validate this model on an independent population. METHODS: We studied 755 consecutive patients treated at Institut Curie for operable breast cancer with sentinel node biopsies in 2009. The multivariate model, including age, tumor size, lymphovascular invasion and interaction covariate between ER and HER2 status, was used to calculate the theoretical risk of positive sentinel lymph node (SLN) for all patients. The performance of the model on our population was then evaluated in terms of discrimination (area under the curve AUC) and of calibration (Hosmer-Lemeshow HL test). RESULTS: our population was significantly different from the training population for the following variables: median tumor size in mm, lymphovascular invasion, positive ER and age. The nomogram showed similar results in our population than in the training population in terms of discrimination (AUC=0.72 [0.68-0.76] versus 0.73 [0.7-0.75] and calibration (HL p=0.4 versus p=0.35). CONCLUSIONS: Despite significant differences between the two populations concerning variables which are part of the nomogram, the model was validated in our population. This nomogram is robust over time to predict the likelihood of positive SLN according to molecular subtypes defined by surrogate markers ER and HER2 determined by immunohistochemistry in clinical practice