Potential histological discordance revealed by second review in the national rare gynecological cancer network (TMRG).

INTRODUCTION: Since 2010, the network of rare malignant tumors of the ovary (TMRG) was developed to optimize the management of patients, also allowing a histological second opinion of rare ovarian tumors. The aim of this work was to study the contribution of second opinion to improve histological diagnostic accuracy on ovarian rare malignant tumors included in the TMRG database. MATERIAL AND METHODS: Histological data of patients diagnosed with a rare ovarian tumor included in TMRG network over a one-year period (2018) were collected. Initial diagnoses were compared with second opinion from national gynecological pathologist experts. The modalities of histological second opinion requests were studied, as well as the histological characteristics of the tumors. The discordances were classified as minor (if the modification of histological diagnosis did not change patient management) and major (if the patient management can be modified). RESULTS: Of 1185 included patients, 937 matched the inclusion criteria. Full concordance between primary diagnosis and expert second opinion was reached in 611 cases (65,3%), minor discordance was seen in 114 (12,2%) and major discordance in 209 (22,3%) of cases. In systematic review requested by the network, 26% (n = 137) of cases were reported with a change in histological diagnosis, while the change concerned 44% (n = 186) of cases for a second opinion spontaneously requested by the initial pathologist. The discrepancies concerned all categories of ovarian tumors, with a majority of mucinous tumors (43% of major discordances), followed by stromal and sex-cord tumors (13.8% of major discordances) and clear cell tumors (12,4% of major discordances). CONCLUSION: This analysis confirms the diagnostic difficulty of ovarian tumors, due to their rarity and morphological heterogeneity. French pathologists are aware of these difficulties and spontaneously refer ovarian tumors with unusual histology for a second opinion and collaborate with rare tumor networks for systematic review.

Predictive factors of pathologic complete response of HER2-positive breast cancer after preoperative chemotherapy with trastuzumab: development of a specific predictor and study of its utilities using decision curve analysis.

PURPOSE: The aim of this study was to assess the Institut Gustave Roussy/M.D. Anderson Cancer Center (IGR/MDACC) nomogram in predicting pathologic complete response (pCR) to preoperative chemotherapy in a cohort of human epidermal growth factor receptor 2 (HER2)-positive tumors treated with preoperative chemotherapy with trastuzumab. We then combine clinical and pathological variables associated with pCR into a new nomogram specific to HER2-positive tumors treated by preoperative chemotherapy with trastuzumab. PATIENTS AND METHODS: Data from 270 patients with HER2-positive tumors treated with preoperative chemotherapy with trastuzumab at the Institut Curie and at the Georges François Leclerc Cancer Center were used to assess the IGR/MDACC nomogram and to subsequently develop a new nomogram for pCR based on multivariate logistic regression. Model performance was quantified in terms of calibration and discrimination. We studied the utility of the new nomogram using decision curve analysis. RESULTS: The IGR/MDACC nomogram was not accurate for the prediction of pCR in HER2-positive tumors treated by preoperative chemotherapy with trastuzumab, with poor discrimination (AUC = 0.54, 95% CI 0.51-0.58) and poor calibration (p = 0.01). After uni- and multivariate analysis, a new pCR nomogram was built based on T stage (TNM), hormone receptor status, and Ki67 (%). The model had good discrimination with an area under the curve (AUC) at 0.74 (95% CI 0.70-0.79) and adequate calibration (p = 0.93). By decision curve analysis, the model was shown to be relevant between thresholds of 0.3 and 0.7. CONCLUSION: To the best of our knowledge, ours is the first nomogram to predict pCR in HER2-positive tumors treated by preoperative chemotherapy with trastuzumab. To ensure generalizability, this model needs to be externally validated.

HER2-positivity rates in breast cancer: no variation over time when clinicopathological features and testing are stable.

HER2 status is essential for breast cancer subtyping and for systemic treatment decisions as patients with HER2-positive tumours can benefit from anti-HER2 targeted therapies. However, few data are available on the current HER2-positive breast cancers rate and its evolution across years. Using data from the Côte d'Or breast cancer registry, we identified, between 1998 and 2011, 3220 women with invasive breast cancer diagnosed in the same laboratory which carries out regular internal quality controls and participates in multiannual international quality control programmes. Throughout the studied period of time, despite an increase of annual breast cancer cases, HER2 positivity rate remained stable (13.1%; P = 0.495), as did the proportion of tumours with positive hormone receptor status (P = 0.467) and the proportion of SBR grade II/III tumours (P = 0.747). Other characteristics, less strongly associated with HER2-positive status, showed either no annual variation (nodal and metastatic status, tumour size) or an annual positive trend (mean age, lobular carcinomas) or an annual negative trend (ductal carcinomas). These data reveal that in a population with stable clinical and pathological characteristics, and with the use of standardised assays, HER2 positivity rate remains stable over time. These results also emphasise that current HER2 positivity rate is lower than initially reported.

Stage IV breast cancer: a population-based study about prognostic factors according to HER2 and HR status.

We aim to describe trends in net survival (NS) and to assess the prognostic factors among women with de novo metastatic breast cancer (MBC) according to human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status. Data on women suffering from de novo MBC and diagnosed from 1998 to 2009 were provided by the Côte-d'Or breast cancer registry. NS was described using the Pohar Perme estimator and prognostic factors were investigated in a generalised linear model. We identified 232 patients (mean age = 64.7). Median NS was 29.2 months, 1- and 5-year NS were 76% and 26% respectively. The survival trend in patients with HER2-positive tumours who did not receive trastuzumab was similar to that in women with triple-negative tumours. A higher relative excess risk of death by cancer was observed for high-grade tumours [RER, relative excess rates = 1.76 (95% CI, confidence intervals: 1.17-2.62) for Scarff Bloom Richardson grade 3 vs. 1 + 2], while a lower risk was observed for luminal tumours [RER = 0.49 (95% CI: 0.27-0.89)] and HER2-positive tumours treated with trastuzumab [RER = 0.28 (95% CI: 0.14-0.59)], both compared with triple-negative tumours. Surgery of the primary tumour was associated with better survival [RER = 0.43 (95% CI: 0.28-0.68)]. With half of the women dead before 29 months, stage IV breast cancer still has a bleak outlook. Progress should continue with new target therapies for both HR and HER2 receptors.

Impact of neoadjuvant chemotherapy on survival in breast cancer patients in daily practice: a population-based study.

This population-based study aimed to describe the effects of neoadjuvant chemotherapy (NC) on survival in breast cancer (BC) patients in daily practice. BC patients treated with NC followed by surgery and radiotherapy, were retrospectively selected from 1982 to 2005 using the Côte d'Or BC registry. These patients were matched for the baseline AJCC (American Joint Committee on Cancer) stage, age at diagnosis, date of diagnosis and oestrogens receptors status to those who had undergone surgery followed by adjuvant chemotherapy and radiotherapy. The prognostic effect of NC on survival in BC patients was assessed with relative survival (RS) analyses. From 1982 to 2005, 210 patients with BC diagnosed in Côte d'Or were treated with NC followed by surgery and radiotherapy. For these patients, mean age at diagnosis was 50 (SD = 11). The main tumour characteristics were clinical AJCC stage 3 (46%) and an advanced Scarff Bloom and Richardson (SBR) stage (80%). Breast conserving surgery was performed in 84 patients (40%), 151 patients (72%) were treated with anthracyclines as the NC and the 5-year RS rate was 71%. Among these patients, 92 (37%) were matched. In this population, multivariate analyses showed that the use of NC did not independently influence RS: relative excess risk = 0.93 (0.50, 1.71).

Changes in 18F-FDG tumor metabolism after a first course of neoadjuvant chemotherapy in breast cancer: influence of tumor subtypes.

BACKGROUND: The aim of this study is to evaluate the impact of the different breast cancer subtypes on the tumor (18)F-FDG uptake at baseline and on its changes after the first course of neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: One hundred and fifteen women with newly diagnosed, large or locally advanced breast cancer undergoing NAC were included. Estrogen receptor (ER), progesterone receptor (PR) and HER2 status were used to define three major tumor subtypes: triple negative (TN) (ER-/PR-/HER2-), luminal (ER+ and/or PR+; HER2-) and HER2 positive (HER2+). Using Fluorine-18 fluorodeoxyglucose positron emission tomography, the tumoral standard uptake value (SUV) maximal index was measured at baseline and just before the second course of NAC. RESULTS: TN tumors presented the highest baseline SUV (11.3 ± 8.5; P < 0.0001). The decrease of SUV after the first course of NAC (ΔSUV) was significantly higher in TN and HER2-positive subtypes (-45% ± 25% and -57% ± 30%, respectively) than in luminal one (-19% ± 35%; P < 0.0001). ΔSUV was a predictive factor of the pathological complete response only in HER2-positive tumors (cut-off = -75%; P < 0.03) with an accuracy of 76%. CONCLUSION: The baseline (18)F-FDG tumoral uptake but also its early response to NAC is different according to the immunohistological subtypes of breast cancer.

FOXP3 expression in cancer cells and anthracyclines efficacy in patients with primary breast cancer treated with adjuvant chemotherapy in the phase III UNICANCER-PACS 01 trial.

BACKGROUND: Predictive markers of response to chemotherapy are lacking in breast cancer patients. Forkhead Box Protein 3 (FOXP3) is an anti-oncogene whose absence in cancer cells could confer resistance to DNA damaging agent. So we made the hypothesis that FOXP3 expression predicts the response to anthracyclines in breast cancer patients and that adjuvant chemotherapy adding taxanes to anthracyclines confers an overall survival (OS) benefit over anthracyclines alone, in patients with FOXP3-negative tumors. PATIENTS AND METHODS: Expression of FOXP3 in cancer cells was evaluated by immunohistochemistry in tumor samples from 1097 patients who participated in the PACS01 randomized trial that evaluated in adjuvant setting the adjunction of docetaxel (Taxotere) to anthracyclines in patients with localized breast cancer. Kaplan-Meier analysis and Cox regression model were used to assess OS according to the presence or absence of FOXP3 expression in tumor cells. RESULTS: Four hundred and five tumors were found to express FOXP3 (37%). FOXP3 expression in breast cancer cells was associated with better OS (P = 0.003). Uni- and multivariate survival analyses according to treatment arm revealed that FOXP3 expression in breast cancer cells is independently associated with improved OS in patients treated with anthracycline-based adjuvant chemotherapy, but not in patients treated with sequential anthracycline-taxane. Moreover, in vitro experiments showed that FOXP3 induction in breast cancer cell lines using histone deacetylase inhibitor enhances anthracyclines efficacy. CONCLUSION: FOXP3 expression in tumor cells may be an accurate predictive biomarker of anthracycline efficacy in breast cancer.

[Retinal vascular network: Changes with aging and systemic vascular disease (cardiac and cerebral)]. / Caractéristiques vasculaires rétiniennes : modifications lors du vieillissement et en pathologie vasculaire systémique (cardiaque et cérébrale).

For over 10 years, the description of the retinal microvascular network has benefited from the development of new imaging techniques. Automated retinal image analysis software, as well as OCT angiography (OCT-A), are able to highlight subtle, early changes in the retinal vascular network thanks to a large amount of microvascular quantitative data. The challenge of current research is to demonstrate the association between these microvascular changes, the systemic vascular aging process, and cerebrovascular and cardiovascular disease. Indeed, a pathophysiological continuum exists between retinal microvascular changes and systemic vascular diseases. In the Montrachet study, we found that a suboptimal retinal vascular network, as identified by the Singapore I Vessel Assessment (SIVA) software, was significantly associated with treated diabetes and an increased risk of cardiovascular mortality. In addition, we supplemented our research on the retinal vascular network with the use of OCT-A. In the EYE-MI study, we showed the potential role of quantitative characterization of the retinal microvascular network by OCT-A in order to assess the cardiovascular risk profile of patients with a history of myocardial infarction. A high AHA (American Heart Association) risk score was associated with low retinal vascular density independently of hemodynamic changes. Thus, a better understanding of the association between the retinal microvasculature and macrovascular disease might make its use conceivable for early identification of at-risk patients and to suggest a personalized program of preventative care. The retinal vascular network could therefore represent an indicator of systemic vascular disease as well as an interesting predictive biomarker for vascular events.

[Dupilumab-related blepharoconjunctivitis: Recommendations of the CEDRE group. Atopic dermatitis, conjunctivitis and dupilumab: Which management approach?] / Blépharo-conjonctivites sous dupilumab : recommandations du groupe CEDRE. Dermatite atopique, conjonctivites et dupilumab : quelle prise en charge ?

Dupilumab is a recombinant monoclonal IgG4 type antibody which inhibits IL4 and IL13 signaling. It is indicated in moderate to severe atopic dermatitis (AD) in adults and adolescents over 12 years of age. Its side effects include conjunctivitis and blepharoconjunctivitis, affecting between 4.7% and 28% of patients depending on the study. The incidence of conjunctivitis in patients treated with dupilumab for AD appears to be higher than placebo in clinical studies. This increase was not observed in patients treated with dupilumab for asthma or sinonasal polyposis. The risk factors for conjunctivitis in patients with AD are disease severity, pre-existence of conjunctivitis and low concentrations of dupilumab, but the pathophysiology of this disease is poorly understood. A literature search carried out in April and May 2020 showed an increase in the number of publications on the subject, but there are currently no official joint dermatologist-ophthalmologist recommendations for prevention and management. The objective of this article is to provide an overview of the status of this subject, to address the main questions raised by this type of conjunctivitis and to suggest a course of action for starting and continuing treatment with dupilumab in patients with AD, according to the recommendations of the French Ophthalmologist/Dermatologist group CEDRE.

T-bet expression in intratumoral lymphoid structures after neoadjuvant trastuzumab plus docetaxel for HER2-overexpressing breast carcinoma predicts survival.

BACKGROUND: In HER2-overexpressing breast cancer, accumulating preclinical evidences suggest that some chemotherapies, like trastuzumab, but also taxanes, are able to trigger a T helper 1 (Th1) anticancer immune response that contribute to treatment success. T helper 1 immune response is characterised by the expression of the transcription factor T-bet in CD4 T lymphocytes. We hypothesised that the presence of such T cells in the tumour immune infiltrates following neoadjuvant chemotherapy would predict patient survival. METHODS: In a series of 102 consecutive HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy incorporating antracyclines or taxane and trastuzumab, we studied by immunohistochemistry the peritumoral lymphoid infiltration by T-bet+ lymphocytes before and after chemotherapy in both treatment groups. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS). RESULTS: Fifty-eight patients have been treated with trastuzumab-taxane and 44 patients with anthracyclines-based neoadjuvant chemotherapy. The presence of T-bet+ lymphocytes in peritumoral lymphoid structures after chemotherapy was significantly more frequent in patients treated with trastuzumab-taxane (P=0.0008). After a median follow-up of 40 months, the presence of T-bet+ lymphocytes after neoadjuvant chemotherapy confers significantly better RFS (log-rank test P=0.011) only in patients treated with trastuzumab-taxane. In this population, multivariate Cox regression model showed that only the presence of T-bet+ lymphocytes in peritumoral lymphoid structures after neoadjuvant chemotherapy was independently associated with improved RFS (P=0.04). CONCLUSION: These findings indicate that the tumour infiltration by T-bet+ Th1 lymphocytes following neoadjuvant trastuzumab-taxane may represent a new independent prognostic factor of improved outcome in HER2-overexpressing breast carcinoma.

Long-term follow-up of HER2-overexpressing stage II or III breast cancer treated by anthracycline-free neoadjuvant chemotherapy.

BACKGROUND: Very effective trastuzumab-based primary systemic therapy (PST) can be proposed for conservative surgery purpose to human epidermal growth factor receptor 2 (HER2)-positive breast cancer (HER2+BC). Long-term follow-up (LTFU) warrants further data. PATIENTS AND METHODS: LTFU of patients, with stage II/III HER2+BC, treated by trastuzumab associated with docetaxel (Taxotere(®)) and/or carboplatin used as anthracycline-free PST was studied. RESULTS: Among 135 patients, with a median follow-up of 48.3 months [95% confidence interval (CI) 45.3-52.4 months], the relapse-free survival (RFS) rate was 73.2% (95% CI 63.76% to 80.55%) while the overall survival (OS) rate was 91.87% (95% CI 84.23% to 95.90%). Adjuvant trastuzumab favorably influenced RFS in univariate analysis while the pathological nodal invasion unfavorably influenced RFS [Cox multivariate analysis (hazard ratio = 2.80, 95% CI 1.36-5.76, P = 0.0052)] and OS. Cardiac toxicity was minor (2.2% transient, reversible asymptomatic decrease in left ventricular ejection fraction). CONCLUSION: This is the first report of LTFU showing that anthracycline-free trastuzumab-based PST combined either with docetaxel and/or carboplatin can achieve, without cardiac toxicity, very competitive results in terms of pathological complete response, RFS and OS, in HER2+BC. The choice of this schedule could be proposed to patients with vascular contraindication for anthracyclines or because patient's or physician's preference for a taxane-only schedule.

Demographic characteristics and opportunistic diseases associated with attrition during preparation for antiretroviral therapy in primary health centres in Kibera, Kenya.

Using routine data from HIV-positive adult patients eligible for antiretroviral therapy (ART), we report on routinely collected demographic characteristics and opportunistic diseases associated with pre-ART attrition (deaths and loss to follow-up). Among 2471 ART eligible patients, enrolled between January 2005 and November 2008, 446 (18%) were lost to attrition pre-ART. Adjusted risk factors significantly associated with pre-ART attrition included age <35 years (Odds Ratio, OR 1.4, 95% Confidence Interval, CI 1.1-1.8), severe malnutrition (OR 1.5, 95% CI 1.1-2.0), active pulmonary tuberculosis (OR 1.6, 95% CI 1.1-2.4), severe bacterial infections including severe bacterial pneumonia (OR 1.9, 95% CI 1.2-2.8) and prolonged unexplained fever (>1 month), (OR 2.6, 95% CI 1.3-5.2). This study highlights a number of clinical markers associated with pre-ART attrition that could serve as 'pointers' or screening tools to identify patients who merit fast-tracking onto ART and/or closer clinical attention and follow-up.

Pathological complete response and survival according to the level of HER-2 amplification after trastuzumab-based neoadjuvant therapy for breast cancer.

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.

[Comparing prediction performances of 18F-FDG PET and CGFL/Curie nomogram to predict pathologic complete response after neoadjuvant chemotherapy for HER2-positive breast cancers]. / Comparaison des performances prédictives du TEP-TDM et du nomogramme CGFL/Curie pour prédire la réponse histologique complète après chimiothérapie néo-adjuvante des cancers du sein HER2-positifs.

OBJECTIVES: The aim of this study was to compare the value of 18F-fluorodesoxyglucose positron emission tomography (18F-FDG PET/CT) with CGFL/Curie nomogram to predict a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor 2 (HER2)-positive breast cancer treated by trastuzumab. METHODS: Fifty-one women with HER2-positive breast cancer treated with trastuzumab plus taxane-based NAC were retrospectively included from January 2005 to December 2015. For 18F-FDG PET/CT, the analyzed predictor was the maximum standardized uptake value of the primary tumor and axillary nodes after the first course of NAC (PET2.SUVmax). pCR was defined by no residual infiltrative tumor but in situ tumor was accepted. Accuracy of CGFL/Curie nomogram and PET2.SUVmax was evaluated measuring sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). Combined prediction was evaluated testing predictor's associations. RESULTS: For CGFL/Curie nomogram's performances, Se, Sp, PPV and NPV were respectively: 76% (95%CI: 58-90%), 57% (95%CI: 43-66%), 55% (95%CI: 42-65), 77% (95%CI: 59-90%). For PET2.SUVmax's performances, Se, Sp, PPV and NPV were respectively: 67% (95%CI: 48-81%), 77% (95%CI: 64-97%), 67% (95%CI: 48-82%), 77% (95%CI: 64-87%). ROC curves for these predictors were similar; the areas under the curve were 0.6 (95%CI: 0.56-0.64) for PET2.SUVmax and 0.55 (95%CI: 0.50-0.59) for CGFL/Curie nomogram. Combined prediction was efficient with Se at 80%, VPN at 76%, Sp at 78% and VPP at 81%. CONCLUSIONS: CGFL/Curie nomogram and PET2.SUVmax were two efficient predictors of pCR in patients with HER2-positive breast cancer. Combined prediction has an improved accuracy.

Influence of cardiac hemodynamic variables on retinal vessel density measurement on optical coherence tomography angiography in patients with myocardial infarction.

INTRODUCTION: Quantitative measurements of retinal microvasculature by optical coherence tomography angiography (OCT-A) have been used to assess cardiovascular risk profile. However, to date, there are no studies focusing on OCT-A imaging in the setting of the altered hemodynamic status found in high-risk cardiovascular patients. METHODS: To determine the potential association between retinal vascular density on OCT-A and a comprehensive battery of hemodynamic variables in patients with myocardial infarction (MI) using data from the acute phase and at 3 months follow-up after cardiac rehabilitation. This prospective longitudinal study included patients who presented with MI in the cardiology intensive care unit at Dijon University Hospital. Main outcomes and measurements were retinal vessel density on OCT-A, hemodynamic status based on left ventricular ejection fraction (LVEF), and indexed cardiac output during the acute phase of myocardial infarction and at 3 months follow-up. RESULTS: Overall, 30 patients were included in this pilot study. The median (IQR) age was 64 years (55-71) with 87% men. At admission, the mean (SD) LVEF was 53% (11), and the mean indexed cardiac output was 2.70 (0.83) L/min/m2. On OCT-A, the mean inner retinal vascular density was 19.09 (2.80) mm-1. No significant association was found between retinal vascular density and hemodynamic variables. CONCLUSION: We found no significant association between retinal vascular density on OCT-A and hemodynamic variables in the acute phase of a myocardial infarction or after 3 months of cardiac rehabilitation. Therefore, OCT-A findings do not seem to be influenced by the hemodynamic changes associated with myocardial infarction.

Prognostic factors of overall survival for patients with FIGO stage IIIc or IVa ovarian cancer treated with neo-adjuvant chemotherapy followed by interval debulking surgery: A multicenter cohort analysis from the FRANCOGYN study group.

INTRODUCTION: The aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer (OC) treated by neo-adjuvant chemotherapy (NAC) followed by interval debulking surgery. MATERIALS AND METHODS: Data from 483 patients with ovarian cancer were retrospectively collected, from January 1, 2000 to December 31, 2016, from the FRANCOGYN database, regrouping data from 11 centers specialized in ovarian cancer treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival. RESULTS: The median overall survival was 52 after a median follow up of 30 months. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or para-aortic lymphadenectomy (p = 0.002), residual disease (CC1/CC2/CC3) after surgery (p < 0.001), positive cytology after NAC (p < 0.001), omental disease after NAC (p = 0.002), no pathologic complete response (pCR) (p = 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16-3.21), p = 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01-2.55), p = 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC. CONCLUSION: In this first and largest French based retrospective study, complete cytoreductive surgery in ovarian cancer remains the main prognostic factor of overall survival.

Gene expression profile and response to trastuzumab-docetaxel-based treatment in breast carcinoma.

BACKGROUND: Resistance to trastuzumab is often observed in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been shown to involve multiple potential mechanisms. We examined the ability of microarray analyses to determine the potential markers of pathological complete response (pCR). METHODS: We conducted an analysis of tumours from 38 patients with locally advanced HER2-positive breast cancer who had received trastuzumab combined with docetaxel. Quantitative reverse transcriptase (RT)-PCR was used to assess the expression of 30 key genes; microarray analyses were carried out on 25 tumours to identify a prognostic gene expression profile, with 13 blinded samples used to validate the identified profile. RESULTS: No gene was found to correlate with response by RT-PCR. The microarray analysis identified a gene expression profile of 28 genes, with 12 upregulated in the pCR group and 16 upregulated in non-pCR. The leave-one-out cross-validation test exhibited 72% accuracy, 86% specificity, and 55% sensitivity. The 28-gene expression profile classified the 13 validation samples with 92% accuracy, 89% specificity, and 100% sensitivity. CONCLUSION: Our results suggest that genes not involved in classical cancer pathways such as apoptosis or DNA repair could be involved in responses to a trastuzumab-docetaxel-based regimen. They also describe for the first time a gene expression signature that predicts trastuzumab response.