Charlotte Ngo

Antimicrobial activity of mucosal-associated invariant T cells

Mucosal-associated invariant T lymphocytes (MAIT lymphocytes) are characterized by two evolutionarily conserved features: an invariant T cell antigen receptor (TCR) α-chain and restriction by the major histocompatibility complex (MHC)-related protein MR1. Here we show that MAIT cells were activated by cells infected with various strains of bacteria and yeast, but not cells infected with virus, in both humans and mice. This activation required cognate interaction between the invariant TCR and MR1, which can present a bacteria-derived ligand. In humans, we observed considerably fewer MAIT cells in blood from patients with bacterial infections such as tuberculosis. In the mouse, MAIT cells protected against infection by Mycobacterium abscessus or Escherichia coli. Thus, MAIT cells are evolutionarily conserved innate-like lymphocytes that sense and help fight off microbial infection.

Intraoperative Ultrasound Localization of Nonpalpable Breast Cancers

BackgroundPreoperative localization of nonpalpable breast cancers requires good coordination between imaging and surgery departments, and insertion of a guide wire can be traumatic for the patient. This study was designed to evaluate the efficacy of intraoperative ultrasound localization of nonpalpable breast cancers directly by the surgeon.MethodsThis prospective study was conducted from June 2006 to October 2006 in 70 patients who underwent surgery for nonpalpable invasive breast cancer. Ultrasound was performed in the operating room by the surgeon with the patient in the operative position. Tumor identification, the correlation with tumor diameter on preoperative ultrasound, analysis of resection margins, and the need to perform surgical re-excision were analyzed.ResultsIntraoperative ultrasound identified the target in 67 (95.7%) of 70 patients. Two of the three lesions not detected by intraoperative ultrasound were ≤5 mm in diameter in patients with a body mass index of ≥25 (normal range, 19–24). The correlation with diagnostic ultrasound for tumor dimensions was satisfactory (correlation coefficient r = .80). Resection margins free of invasive lesions were obtained in 66 cases (94.3%). Three patients (4.3%) required surgical re-excision, one mastectomy due to multifocal cancer, and two lumpectomy due to positive resection margins.ConclusionsIntraoperative ultrasound localization of nonpalpable breast cancers is feasible and effective, with a sensitivity of 98.3% for tumors >5 mm. It spares the patient the discomfort of a radiological and/or supplementary examination with insertion of a guide wire. It also saves time and money for hospital teams.

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.

Reasons of not having breast reconstruction: a historical cohort of 1937 breast cancer patients undergoing mastectomy.

BackgroundThe aims of the study were to investigate the factors associated with not having breast reconstruction following mastectomy and to assess patient satisfaction with information on reconstruction.Patients and methodsWe analysed a historical cohort of 1937 consecutive patients who underwent mastectomy at Institut Curie between January 2004 and February 2007. Their sociodemographic and clinicobiological characteristics were recorded in a prospective database. A questionnaire was sent to 10% of nonreconstructed patients.ResultsThe proportion of patients with invasive cancer was 82.7%. The rate of nonreconstruction in patients with in situ and invasive cancer was 34.6% and 74.9%, respectively. On multivariate analysis, only employment outside the home was associated with reconstruction in patients with in situ cancer (p < 0.001). In patients with invasive cancer, employment status (p < 0.001) and smoking (p = 0.045) were associated with reconstruction, while age > 50, ASA score >1, radiotherapy (p < 0.0001) and metastatic status (p = 0.018) were associated with nonreconstruction. For 80% of questionnaire responders, nonreconstruction was a personal choice, mainly for the following reasons: refusal of further surgery, acceptance of body asymmetry, risk of complications and advanced age. Information on reconstruction was entirely unsatisfactory or inadequate for 62% of patients.ConclusionBetter understanding the factors that influence decision of nonreconstruction can help us adapt the information to serve the patient’s personal needs.

Outcome in early cervical cancer following pre-operative low dose rate brachytherapy: A ten-year follow up of 257 patients treated at a single institution

OBJECTIVE To report the outcome of preoperative low dose rate uterovaginal brachytherapy (LDR-UVBT) followed by radical surgery in the treatment of early cervical carcinoma. METHODS 257 patients treated at Institut Curie from 1985 to 2008 for cervical carcinoma less than 4cm (FIGO stages Ib1, IIA and IIB) were studied. Patients received preoperative LDR-UVBT followed by hysterectomy Piver II type, with pelvic lymph nodes dissection (PLND). Predictive factors for pathological response to brachytherapy were analyzed with logistic regression, as well as survival rates. RESULTS 44% of patients had residual tumor, 4.3% of patients had parametrial invasion and 17.9% of patients had lymph node involvement. Predictive factors for an incomplete pathological response were: initial clinical tumor size 20mm (OR 2.1), pN1 (OR 2.77), glandular carcinoma (OR 2.51) and lymphovascular invasion (OR 4.35). 7.4% and 2.7% of patients had respectively grade 2 and grade 3 post-therapeutic late complications. Median follow up was 122 months [1-282]. Five-year actuarial overall survival and disease free survival were respectively 83% CI [78.3-87.5] and 80.9% CI [76.3-85.7]. In multivariate analysis, factors affecting significantly the overall survival and disease free survival rates were: lymph node involvement (RR 4.53 and 8.96 respectively), parametrial involvement (RR 5.69 and 5.62 respectively), smoking (RR 3.07 and 2.63 respectively). CONCLUSIONS Preoperative LDR-UVBT results in good disease control with a low complications rate. Its accuracy could be improved by a better selection of patients. Lymph nodes and parametrial evaluation remains a challenging issue that should be achieved with imaging and minimal invasive surgery.

Clinico-pathology and prognosis of endometrial cancer in patients previously treated for breast cancer, with or without tamoxifen: A comparative study in 363 patients

OBJECTIVE To compare the clinic-pathologic variables and the prognosis of endometrial cancer in patients with and without previous breast cancer, with and without Tamoxifen. METHODS We analyzed patients treated for an endometrial carcinoma from 1994 to 2004: patients without breast cancer (group 1), patients with a previous breast cancer without tamoxifen (group 2) and patients treated for breast cancer with tamoxifen (group 3). Survival rates were calculated according to Kaplan-Meier method and compared using a Log rank test, multivariate analysis was performed with a Cox regression model. RESULTS 363 patients were analyzed. 80 patients had a previous history of breast cancer (43 received tamoxifen). Although it was not statistically significant, more carcinosarcomas were observed in patients in group 3 than patients in groups 1 and 2 (11.7% versus 4.2% and 5.4% respectively, p = 0.17).) Median follow-up was 87 months [2-185]. 5-year overall survival rate was respectively in groups 1, 2 and 3: 82%, 73.2%, and 61% (p = 0.0006). 5-year local relapse-free survival rate was respectively: 95.9%, 93.1% and 82.5% (p = 0.02). In multivariate analysis, factors affecting overall survival rate were: age ≥65 ans (HR 3.62, p < 0.0001), FIGO stage (HR 3.33 p < 0.0001 for locally advanced stage versus early stage, HR 8.87 p = 0.03 for distant extension versus early stage), and group 3 (HR 2.83 p < 0.001 versus group 1). CONCLUSION Patients with endometrial cancer previously treated for breast cancer show a worse prognostic, particularly if they reveived tamoxifen.

From prospective biobanking to precision medicine: BIO-RAIDs – an EU study protocol in cervical cancer

BackgroundCervical cancer (CC) is -second to breast cancer- a dominant cause of gynecological cancer-related deaths worldwide. CC tumor biopsies and blood samples are of easy access and vital for the development of future precision medicine strategies.DesignBIO-RAIDs is a prospective multicenter European study, presently recruiting patients in 6 EU countries. Tumor and liquid biopsies from patients with previously non-treated cervical cancer (stages IB2-IV) are collected at defined time points. Patients receive standard primary treatment according to the stage of their disease. 700 patients are planned to be enrolled. The main objectives are the discovery of -dominant molecular alterations, -signalling pathway activation, and -tumor micro-environment patterns that may predict response or resistance to treatment. An exhaustive molecular analysis is performed using 1° Next generation sequencing, 2° Reverse phase protein arrays and 3° Immuno-histochemistry.DiscussionThe clinical study BIO-RAIDs is activated in all planned countries, 170 patients have been recruited till now. This study will make an important contribution towards precision medicine treatments in cervical cancer. The results will support the development of clinical practice guidelines for cervical cancer patients to improve their prognosis and their quality of life.Trial registrationClinicaltrials.gov: NCT02428842, registered 10 February 2015.

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

BACKGROUND 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.

Heterogeneous Amplification of HER2 Is a Rare but Clinically Significant Event in Invasive Ductal Carcinoma.

BackgroundWe have recently shown that pT1ab HER2 positive tumors carry a poor prognosis, which may be alleviated by trastuzumab (T) based therapy (Rodrigues et al, ASCO 2009). We had also reported that heterogeneous expression of HER2 (hetHER2) may be associated with a poor outcome depending on the HER2 overexpressing subclone (Cottu et al, Ann Oncol 2007). Meanwhile, ASCO/CAP guidelines have questioned the minimum valid score for HER2 expression (Moeder et al, J Clin Oncol 2007; Wolff et al, J Clin Oncol 2007). We describe here the characteristics and outcome of a series of patients with hetHER2 disease.Patients and methodsHER2 status is routinely assessed in our institution in advanced breast cancer patients since 1999, and in early patients since 2002. Out of 1300 HER2 positive cases, we have been able to identify 12 pts with heterogeneous expression of HER2 in the primary tumor ( Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6034.

Abstract P2-01-01: Sentinel node surgery after neoadjuvant chemotherapy in patient with axillary node involvement: The French GANEA 2 prospective multi-institutional trial

Background Half of the patient treated with neoadjuvant chemotherapy (NAC) for a large operable breast cancer has no axillary lymph node involvement at the time of surgery. Sentinel lymph node detection (SLND), performed after NAC, must select patient who should be spared of an axillary lymph node dissection (ALND). The application of SLND for staging the axilla after NAC for patient who initially had a proven axillary lymph node involvement remains controversial because of a low detection rate (DR) and a high false negative rate (FNR). Objective The aim of GANEA 2 trial was to assess the DR and the FNR of SLND after NAC in the particular case of patients with a proven axillary lymph node involvement. Patients and Method GANEA 2 was validated by scientific and ethical national boards. Inclusion criteria: FIGO stage T2-T3 infiltrating breast carcinoma, indication of NAC, surgery (radical or conservative) after NAC and signed consent form, Exclusion criteria: inflammatory cancer, local relapse, previous surgical removal of the tumour, mental disorder, pregnancy or no contraceptive method, contra-indication to NAC, NAC interrupted due to progressive disease. Design: Diagnosis and indication to plan a NAC, control of inclusion and exclusion criteria, consent form signature, axillary sonography with fine needle cytology before NAC to select patients with a proven lymph node involvement. After NAC patients underwent both SLND, with the combined technique Blue dye and radiolabeled colloid, and complementary ALND. Pathological procedure: Pathological analysis, of sentinel and non sentinel nodes, carried out according to standard methods and classified according the last American Joint Committee staging system and Sataloff classification. Studied parameters were detection rate, false negative rate and Sataloff grading on tumor and lymph nodes. We evaluated particularly the likelihood that the FNR in patients with one or more SLN examined was greater than 10%. Patients with no lymph node involvement before NAC underwent only a SLND with an ALND only in the case of SLN macro-metastasis with a rigorous follow up. They are not part of this abstract. Results From July 2010, to February 2014, 242 patients from 19 institutions were enrolled, with a proven axillary lymph node involvement before NAC. After NAC, 1/3 had metastasis free axillary lymph node (80/142). Detection rate was 83.1% (201/242). Half of the patients with a detection failure had an involved ALND. The false negative rate was 14.2% in the whole series but 24.5% in the case of only 1 SLN resected, and 8% in case of more than 1 SLN resected. In case of involved SLN, half of the patients had involved ALND. Considering the node Sataloff scoring, 18 of the 20 false negative cases were grade C or D (n=15 grade C, metastatic disease and therapeutic effect; n = 3 grade D, metastasis and no therapeutic effect). Conclusion Among patients treated by NAC for a large operable breast cancer with proven involved lymph node before NAC, who had only 1 SLN examined, the false negative rate was 24.5%. SLND with the combined technique, provides a FNR of less than 10% only in the case of 2 or more SLN resected. Citation Format: Jean-Marc Classe, Loic Campion, Severine Alran, Christine Tunon de Lara, Pierre Francois Dupre, Christelle Faure, Nicolas Paillocher, Serge Lasry, Marie Pierre Chauvet, Gilles Houvenaeghel, Marian Gutowski, Pascaline De Blaye, Charlotte Ngo, Emmanuel Barranger, Jean Luc Veraeghe, Celine Lefebvre, Jean Francois Rodier, Virginie Bordes, Helene Charitansky, Gwenael Ferron, Pierre Gimbergues. Sentinel node surgery after neoadjuvant chemotherapy in patient with axillary node involvement: The French GANEA 2 prospective multi-institutional trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-01.