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Isabelle Ray-Coquard

Publications and source records attributed to Isabelle Ray-Coquard.

At least 19 recordsLinked to original sources
PubMed2026

Long-Term Outcomes in Patients With Recurrent Ovarian Cancer and Exceptional Response to PARP Inhibitors.

IMPORTANCE: A subset of patients with platinum-sensitive recurrent ovarian cancer (PS-ROC) treated with maintenance poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have exceptional response. Although licensing recommends continuing PARP inhibitors until progression or unacceptable toxic effects, the optimal duration of PARP inhibitors, and the risks of late progression, myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML) in patients with exceptional response are unknown. OBJECTIVE: To determine the long-term outcomes of patients with PS-ROC who have exceptional response to PARP inhibitors, and to explore genotype-phenotype associations. DESIGN, SETTING, AND PARTICIPANTS: This was an international, multicenter, retrospective cohort study of patients with exceptional response to PARP inhibitors, defined as patients with PS-ROC and progression-free survival (PFS) of 5 years or longer from PARP inhibitor commencement. The study was conducted across 41 sites in 14 countries from January 11, 2023, to November 10, 2025. EXPOSURES: Treatment with PARP inhibitors. MAIN OUTCOMES AND MEASURES: The primary end point was PFS, and secondary end points included overall survival, toxic effects, and dose reductions. RESULTS: A total of 320 patients with exceptional response (mean [SD] age, 56.4 [9.4] years) were included, with a median follow-up of 6.8 years (95% CI, 6.6-7.0 years). The median (IQR) PARP inhibitor duration was 75.0 (64.0-91.0) months. Of patients with exceptional response, 211 (65.9%) received continuous PARP inhibitors, but 109 (34.1%) discontinued: 34 (10.6%) due to physician recommendation, 2 (7.5%) had disease progression beyond 5 years, 22 (6.9%) had toxic effects, 17 (5.3%) for patient preference, and 12 (3.8%) for another reason. The 7.5-year and 10-year PFS rates were 88.8% (95% CI, 84.5%-93.3%) and 78.7% (95% CI, 70.5%-87.9%), respectively. Among the patients, 85 (26.6%) discontinued PARP inhibitors for reasons other than disease progression, with a 10-year PFS of 90.1% (95% CI, 80.6%-100%) vs 72.5% (95% CI, 60.3%-87.2%) for those who continued taking PARP inhibitors. Five patients (1.6%) were diagnosed with late-onset MDS/AML. Patients with exceptional response were enriched for variants in the BRCA1 RING domain and the BRCA2 DNA-binding domain. CONCLUSIONS AND RELEVANCE: In this cohort study, most patients with exceptional response to PARP inhibitors remained progression free, including those who discontinued PARP inhibitors without progression. The risk of late-onset MDS/AML was low. These results can guide counseling on the duration of maintenance PARP inhibitors in patients with exceptional response and suggest that functional cure may be possible in patients with PS-ROC and exceptional response to PARP inhibitors.

Humans↗
PubMed2025

Beyond BRCA deficiency: Clinical and molecular predictors of survival in patients with BRCA-deficient tubo-ovarian high-grade serous carcinoma.

BRCA-associated homologous recombination deficiency (HRD) is present in ~50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤3 years, n=42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n=1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.

Journal Article↗
PubMed2006

Low serum albumin levels and liver metastasis are powerful prognostic markers for survival in patients with carcinomas of unknown primary site.

BACKGROUND: The authors investigated how lymphopenia and low serum albumin levels correlate with the prognosis of patients with carcinoma of unknown primary (CUP). METHODS: Univariate and multivariate prognostic factor analyses were conducted in a population of 317 consecutive patients with CUP who were evaluated at the Cross Cancer Institute of Edmonton, Alberta, Canada, from 1998 to 2004. RESULTS: The results from multivariate analysis showed that patients who had a performance status >/=2 (using the World Health Organization scale), a high overall comorbidity score (on the Adult Comorbidity Evaluation 27), liver metastasis, elevated serum lactate dehydrogenase (LDH) levels, lymphopenia (defined as an absolute lymphocyte count >/=0.7 x 10(9)/L), and low serum albumin levels had a worse prognosis. Based on the observation that the presence of liver metastasis and low serum albumin levels were the most powerful adverse prognostic factors, a classification scheme was delineated that took those 2 variables into account. A group of good-risk patients (no liver metastasis and normal serum albumin levels) and a group of poor-risk patients (liver metastasis and/or low serum albumin levels) were identified with median survivals of 371 days and 103 days, respectively (P < .0001). This classification was validated further in an independent data set of 124 patients who were evaluated at 2 French cancer centers: Among those patients, the median survival was 378 days in the good-risk group and 90 days in the poor-risk group (P < .0001). The new prognostic model substantially outperformed the previous standard prognostic model, which was based on performance status and serum LDH levels. CONCLUSIONS: Lymphopenia and low serum albumin levels were identified as 2 new independent markers of prognosis in patients with CUP. Although the authors confirmed the validity of the previous prognostic model, they developed and validated a more powerful, simple model based on the 2 most powerful adverse prognostic factors: liver metastasis and low serum albumin levels. These findings were confirmed in an independent cohort of patients with CUP, and consideration of the authors' improved prognostic model for survival of patients with CUP is warranted.

Adult↗
PubMed2006

Brostallicin, an agent with potential activity in metastatic soft tissue sarcoma: a phase II study from the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

The study aimed to assess the efficacy and safety of brostallicin, a new DNA minor groove binder, at a dose of 10mg/m2, intravenous (i.v.) every three weeks, in patients with advanced or inoperable soft tissue sarcoma (STS) and gastrointestinal stromal tumour (GIST) failing first line therapy. Two groups were recruited: (1) GIST following treatment with imatinib; (2) other STS following treatment with single agent doxorubicin or ifosfamide or a single line of combination therapy. The primary end-point was overall response rate (ORR) as defined by response evaluation criteria in solid tumours (RECIST). Progression free survival (PFS) was a secondary end-point. In the GIST group, a Simon two step design was planned: first step 18 patients, total 32 patients (p1=20% p0=5% alpha=beta=0.1). In the non-GIST group, planned sample size was 40 in a standard Fleming one-step design (p0=10%, p1=25%, alpha=beta=0.1). Forty-three patients with non-GIST and 21 patients with GIST were recruited. In general, the drug was well tolerated. Common Toxicity Criteria (CTC) grade 3 or grade 4 toxicity was granulocytopenia: 70% of patients, 50% of cycles; fatigue: 25% of patients, 8% of cycles; febrile neutropenia: 14% of patients, 4% of cycles. There was one confirmed toxic death due to neutropenic septicaemia. Three patients had clinically significant allergic reactions in 249 cycles delivered. In the GIST group, no patients had a confirmed response and recruitment was discontinued at the first step. In the non-GIST group, there were two confirmed partial responses. The 3 month PFS was 46% in the non-GIST group and 33% in the GIST group. In the non-GIST group, this PFS is in the range of other agents considered active in STS, and may predict for more substantial first line activity. Further investigation in STS other than GIST appears warranted.

Adult↗
PubMed2006

Docetaxel and gemcitabine combination in 133 advanced soft-tissue sarcomas: a retrospective analysis.

Advanced soft-tissue sarcomas are usually resistant to cytotoxic agents such as doxorubicin and ifosfamide. Antitumor activity has been observed for gemcitabine and docetaxel combination. We conducted a retrospective study on 133 patients (58 males/75 females) with unresectable or metastatic soft-tissue sarcoma. The median age at diagnosis was 51.7 (18-82), with 76 patients with leiomoyosarcoma and 57 patients with other histological subtypes. The initial localizations were limb (44), uterine (32), retroperitoneal (23) and organs or bone (34). Patients received 900 mg/m2 of gemcitabine (days 1 and 8) over 90 min plus 100 mg/m2 of docetaxel (day 8), intravenously every 21 days. Gemcitabine/docetaxel combination was well tolerated with an overall response of 18.4% and with no clear statistical difference between leiomyosarcomas and other histological subtypes (24.2% versus 10.4% (p=0.06)). No difference was found between uterine soft-tissue sarcomas versus others. The median overall survival was 12.1 months (1-28). Better overall survival was correlated with leiomyosarcoma (p=0.01) and with the quality of the response, even for patients with stable disease (p<10(-4)). No statistical difference was found for the initial localization. Response to treatment and overall survival were better for patients in World Health Organization (WHO) performance status classification (PS) 0 at baseline versus patients in WHO PS-1, 2 or 3 (p=0.023 and p<10(-4), respectively). Gemcitabine/docetaxel combination was tolerable and demonstrated better response and survival for leiomyosarcoma, especially for patients in WHO PS-0 at baseline. For the other histological subtypes, the response was not encouraging, but the survival for patients in response or stable suggests further investigation.

Adolescent↗
PubMed2006

Medical practices and cancer care networks: examples in oncology.

Understanding medical practices or the whys and wherefores of care decision-making is among the major objectives of medical, economic and sociological research in the current political environment. Although variations of medical practice have long been known to exist, causes and deciding factors remain obscure. This is one of the reasons why medical auditing became widely used in the past years. Using methods similar to those of clinical research, we will explore existing medical practices and their implications, with the aim to propose possible improvements. Elaborating clinical practice guidelines and promoting cancer network activities might prove promising and have a significant impact on clinical practice. This article provides a state-of-the-art overview of the subject, notably in the domain of oncology where substantial advances are being made.

Humans↗
PubMed2006

[Prognostic factors for febrile neutropenia].

Cytotoxic chemotherapy suppresses the haematopoietic system, impairing host protective mechanisms and limiting the doses of chemotherapy that can be tolerated. Febrile neutropenia, the most serious haematological toxicity, is associated with the risk of life-threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcomes. The recent literature in chemotherapy-induced neutropenia and its complications and impact was provided an update on research, and the implications for improving the management of patients with cancer who are treated with myelosuppressive chemotherapy was discussed. Despite its importance as the primary dose-limiting toxicity of chemotherapy, much concerning neutropenia and its consequences and impact remains unknown. Recent surveys indicate that neutropenia remains a prevalent problem associated with substantial morbidity, mortality, and costs. The colony-stimulating factors (CSFs) have been used effectively in a variety of clinical settings to prevent or treat febrile neutropenia and to assist patients receiving dose-intensive chemotherapy. A meta-analysis of the available randomized controlled trials (RCTs) has confirmed the efficacy of prophylactic CSFs. Much research has sought to identify risk factors that may predispose patients to neutropenic complications, including febrile neutropenia, in an effort to predict better which patients are at risk and to use preventive strategies, such as prophylactic colony-stimulating factors, more cost-effectively. Research in quantifying the risk of neutropenic complications may make it possible in the near future to target patients at greater risk with appropriate preventive strategies, thereby maximizing the benefits and minimizing the costs.

Antibiotic Prophylaxis↗
PubMed2006

[Neoadjuvant chemotherapy and ovarian cancer].

Primary surgical cytoreduction followed by chemotherapy usually is the preferred management of advanced (stage III or IV) ovarian cancer. The presence of residual disease after surgery is one of the most important adverse prognostic factors for survival. Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management of bulky ovarian cancer, with the goal of improving surgical quality. Retrospective analyses suggest that a subgroup of patients with Stage III and IV ovarian carcinoma can be treated with neoadjuvant chemotherapy followed by interval debulking surgery. The absolute indications for neoadjuvant chemotherapy appear to be Stage IV disease (excluding pleural fluid) or metastases of more than 1 g at sites where resection is impossible. Interval debulking surgery in patients with suboptimal primary debulking surgery has been proven effective in increasing overall survival and progression-free survival in a large prospective, randomized trial of the European Organization for Research and Treatment of Cancer (EORTC). GOG evaluated the effect of adding secondary cytoreductive surgery to postoperative chemotherapy. Unfortunately in this study, for patients with advanced ovarian carcinoma in whom primary cytoreductive surgery was considered to be maximal, the addition of secondary cytoreductive surgery to postoperative chemotherapy with paclitaxel plus cisplatin does not improve progression-free survival or overall survival. The strategy of neoadjuvant chemotherapy, followed by interval debulking surgery, should be confirmed in a prospective randomized trial. The EORTC55971 trial is currently addressing this issue.

Female↗
PubMed2006

[Neoadjuvant chemotherapy in sarcoma].

This document describe s the proposed clinical practices guidelines for neoadjuvant chemotherapy in soft tissue sarcomas proposed by the French Sarcoma Group.Neo-adjuvant chemotherapy remains an experimental therapeutic procedure in soft tissue sarcomas. Neo-adjuvant chemotherapy may be proposed in three different types of situations: 1) a locally advanced tumor, non accessible to R0 or 1 removal of the lesion. Its objective is there to allow for R0 or R1 surgical removal of the tumor. 2) A locally advanced tumor, accessible to R0 or 1 removal of the lesion, but with a mutilating surgery (amputation). Its objective is there to allow for R0 or R1 conservative surgical removal of the tumor. In both situation, the strategy should be discussed beforehand in a multidisciplinary specialized consultation for sarcoma. 3) In the case where complete (R0 or R1) surgical removal of the tumor can be performed, neooadjuvant chemotherapy has no demonstrated role. The only randomized phase III clinical trial testing neo-adjuvant chemotherapy in this setting, i.e. the STBSG 62871 STBSG trial, failed to demonstrate any benefit in terms of overall or progression free survival. The selection of the type of chemotherapy regimen given in the neoadjuvant setting should be discussed in a multidisciplinary setting, considering the age and the general status of the patient; young patients, without associated concomittent illnesses should be proposed for a combined chemotherapy regimen, combining doxorubicin (> or = 50 mg/m2) and ifosfamide (> 5 g/m2) on the basis of randomized trials demonstrating an improvement of response rate versus single agent therapy with doxorubine. In elderly and/or frail patients, conversely, single agent doxorubicin may be the preferred option.

Antineoplastic Agents↗
PubMed2005

Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group study.

PURPOSE: The aim of this study was to identify factors predicting initial and late resistance of GI stromal tumor (GIST) patients to imatinib and to document the dose-response relationship in the prognostic subgroups. This study is based on the European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group randomized trial comparing two doses of imatinib in advanced disease. PATIENTS AND METHODS: Initial resistance was defined as progression within 3 months of randomization, and late resistance was defined as progression beyond 3 months. Investigated cofactors include imatinib dose, age, sex, performance status, original disease site, site and size of lesions at trial entry, and baseline hematologic and biologic parameters. RESULTS: Initial resistance was recorded for 116 (12%) of 934 assessable patients and was independently predicted by the presence of lung and absence of liver metastases, low hemoglobin level, and high granulocyte count. Among 818 patients who were alive and progression free at 3 months, 347 subsequent progressions were recorded, and late resistance was independently predicted by high baseline granulocyte count, primary tumor outside of the stomach, large tumor size, and low initial imatinib dose. The impact of initial dose on late resistance was mainly significant in patients with a high baseline granulocyte count (> 5.10(9)/L) and in patients with tumors of GI origin outside of the stomach and small intestine. CONCLUSION: Our study identifies patients for whom initial and/or long-term treatment needs to be improved and patients who require a high initial dose. Correlation of these results with immunohistochemistry and molecular parameters may further help to understand the biologic mechanisms of resistance.

Adult↗
PubMed2005

Lymphopenia: a new independent prognostic factor for survival in patients treated with whole brain radiotherapy for brain metastases from breast carcinoma.

BACKGROUND AND PURPOSE: To determine overall survival (OS) and independent prognostic factors in patients with brain metastases (BM) from breast cancer treated by whole brain radiotherapy (WBR). PATIENTS AND METHODS: One hundred and twenty (120) women with BM, treated in a single French cancer center between 02/91 and 06/01, were reviewed. BM were confirmed by computed tomography or magnetic resonance imaging. Survival time was defined as the time interval from the date of BM to the date of death or last follow-up. A Cox proportional hazards regression model was used to determine significant prognostic factors in a multivariate analysis. RESULTS: Surgery was followed by WBR in 5 patients. One hundred and four (104) patients received exclusive WBR, eight received concomitant chemo-radiation, and one received chemo-radiation after surgery. The median survival time was 5 months (95% CI: 3-7 months). In the multivariate analysis, performance status over 1 and lymphopenia (<0.7 G/L) were found to be independent prognostic factors for poor survival. Based on the number of these independent prognostic factors, we propose a predictive model for survival in brain metastatic cancer patients. Median survival was 7 months for patients presenting none or one poor prognosis factor at diagnosis versus 2 months for patients with 2 poor prognosis factors (p<0.0001) CONCLUSION: Brain metastases from breast cancer remain associated with very poor prognosis and there is a need for better treatment procedures. If confirmed in predictive models, the identification of prognostic subgroups, based on KPS and lymphopenia, among patients with BM from breast cancer would help physicians select patients for future clinical trials.

Adult↗
PubMed2005

Persistence of medical change at implementation of clinical guidelines on medical practice: a controlled study in a cancer network.

PURPOSE: A cancer network of general or private hospitals of a French region was started in 1995 for improving quality of care and rationalizing medical prescriptions. The impact of implementing a clinical practice guidelines (CPG) project assessed conformity with guidelines in medical practice; significant changes were observed within the network, whereas no changes were observed in a control region without cancer network. In the present study, we evaluated the persistence of conformity to guidelines through a new medical audit. PATIENTS AND METHODS: In 1999, the hospitals of the previously compared experimental and control groups accepted to reassess the impact of CPG. A controlled transversal study was performed in the experimental group (cancer network) and in the control group (no regional cancer network). In 1996 (first audit) and in 1999 (present audit), all new patients with colon cancer (177 and 200 in experimental group and 118 and 100 in control group, respectively) and early breast cancer (444 and 381 in experimental group and 172 and 204 in control group, respectively) were selected. RESULTS: In the experimental group, the compliance of medical decisions with CPG was significantly higher in 1999 than in 1996 for colon cancer (73%; 95% CI, 67% to 79% v 56%; 95% CI, 49% to 63%, respectively; P = .003) and similar for the two periods for breast cancer (36%; 95% CI, 31% to 41% v 40%; 95% CI, 35% to 44%, respectively; P = .24). In the control group, compliance was significantly higher in 1999 than in 1996 for colon cancer (67%; 95% CI, 58% to 76% v 38%; 95% CI, 29% to 47%, respectively; P < .001) and identical for the two periods for breast cancer (4%; 95% CI, 1% to 7% v 7%; 95% CI, 3% to 11%, respectively; P = .19). CONCLUSION: The CPG program for cancer management produced persistent changes in medical practice in our cancer network in terms of conformity with CPG.

Adult↗
PubMed2005

[Recommendations for the management of GIST patients].

BACKGROUND: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last years. A national consensus meeting was therefore organized in order to identify the optimal management procedures for patients with GIST in localized and advanced stages. METHODS: A panel of different specialties, including pathology, molecular biology, imaging, surgery, gastroenterology, medical oncology reviewed the current literature, in particular the recent Lugano conference, to identify consensus points and topics for future research in four different working groups: pathology and molecular biology, early management of small tumors and imaging, surgery, and medical treatment. Consensus points were categorized according to the Standard Options Recommendations (SOR) of the French Federation of Cancer Centers. RESULTS: The standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is advisable for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. Resection of metastases is also considered as an experimental procedure which can not be recommended routinely. The criteria for tumor response to imatinib should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield units) on computed tomography, metabolic activity (i.e. reduction of FDG uptake on positron emission tomography), and reduction of vascularisation of the tumors using contrast enhanced ultrasound evaluation. An increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. CONCLUSIONS: Consensus points in clinical management of GIST in this national conference adopted the majority of consensus points published in the Lugano conference. This multidisciplinary work will be published in the reference oncology, gastroenterology, and pathology journals in French languages.

Antineoplastic Agents↗
PubMed2004

CD4 lymphopenia as a risk factor for febrile neutropenia and early death after cytotoxic chemotherapy in adult patients with cancer.

BACKGROUND: Lymphopenia is frequently observed in patients with cancer and correlates with the risk of febrile neutropenia and early death after chemotherapy. The phenotype of the depleted lymphocyte populations was investigated in the current study. METHODS: Peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD19, CD56) were quantified on Day 1 using fluorescence-activated cell sorting in a prospective study of 213 patients with cancer treated with chemotherapy in a single oncology ward during 12 months. Correlations between lymphocyte phenotype, clinical characteristics, and the risk of febrile neutropenia and early death within 31 days after chemotherapy were investigated in univariate and multivariate analyses. RESULTS: Total lymphocyte count and CD3, CD4, and CD8 lymphocyte subsets were significantly lower in patients who experienced febrile neutropenia. Total lymphocyte count and CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were significantly lower in patients who died within 31 days after chemotherapy. Using logistic regression, CD4 lymphopenia (< 450/muL; odds ratio [OR] = 2.9, 95% confidence interval [CI] = 1.5-5.9) and the dose of chemotherapy (OR = 3,9, 95% CI = 2.0-7.8) were both identified as independent risk factors for febrile neutropenia. Fifty-four percent of patients with both risk factors experienced febrile neutropenia. CD4 lymphocyte count < 450/muL was also an independent risk factor for early death (OR = 7.7, 95% CI = 1.7-35). Thirteen percent of patients with a CD4 lymphocyte count </= 450/muL died within 31 days after chemotherapy. Eighty-seven percent (14 of 16) of patients who died before Day 31 had a CD4 lymphocyte count < 450/muL. CONCLUSIONS: A low CD4 count was an independent risk factor for febrile neutropenia and early death in patients receiving cytotoxic chemotherapy.

Adolescent↗
PubMed2004

Dendritic cell infiltration and prognosis of early stage breast cancer.

PURPOSE: Although dendritic cells (DC) and T cells can infiltrate primary breast carcinoma, it remains unclear whether the immune response influences the clinical outcome. EXPERIMENTAL DESIGN: T lymphocytes and DC infiltration within primary tumors was investigated in 152 patients with invasive nonmetastatic breast cancer. CD1a, CD3, CD68, CD123, CD207/Langerin, and CD208/DC-LAMP expression was assessed with semiquantitative immunohistochemical analysis. Expression of chemokines involved in DC migration (MIP-3a/CCL20, MIP-3b/CCL19, and 6Ckine/CCL21) was also examined. The correlation between these markers and the characteristics of the tumors, as well as relapse-free and overall survival was analyzed. Significant prognostic parameters were then tested in a validation series. RESULTS: Infiltration by immature CD207/Langerin+ DC was found in a third of the cancers and did not correlate with clinicopathological data. Presence of mature CD208/DC-LAMP+ DC (56%) and CD3+ T cells (82%) strongly correlated with lymph node involvement and tumor grade. Among the chemokines analyzed, only the presence of MIP-3b/CCL19 in 57% of the tumors correlated with prolonged overall survival. CD123+ plasmacytoid DC (pDC) infiltrated 13% of the primary tumors. Their presence was strongly associated with shorter overall survival (93% versus 58% at 60 months) and relapse-free survival (90% versus 37% at 60 months) and was found to be an independent prognostic factor for overall survival and relapse-free survival and confirmed in an independent validation series of 103 patients. CONCLUSIONS: Infiltration by pDC of primary localized breast tumor correlates with an adverse outcome, suggesting their contribution in the progression of breast cancer.

Adult↗