Biomarqueurs tumoraux circulants

Publications

Année de publication : 2013

F C Bidard, F Huguet, C Louvet, L Mineur, O Bouché, B Chibaudel, P Artru, F Desseigne, J B Bachet, C Mathiot, J Y Pierga, P Hammel (2013 May 17)

Circulating tumor cells in locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the LAP 07 trial.

Annals of oncology : official journal of the European Society for Medical Oncology / ESMO : 2057-61 : DOI : 10.1093/annonc/mdt176 En savoir plus
Résumé

Pancreatic carcinoma is one of the leading causes of cancer-related mortality. At the time of diagnosis, 30% of patients present with a locally advanced pancreatic carcinoma (LAPC). As circulating tumor cells (CTCs) count may be a surrogate of the cancer metastatic abilities, CTC detection rates and prognostic value were studied in a prospective cohort of LAPC patients.

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François-Clément Bidard, Jean-Yves Pierga, Jean-Charles Soria, Jean Paul Thiery (2013 Feb 6)

Translating metastasis-related biomarkers to the clinic–progress and pitfalls.

Nature reviews. Clinical oncology : 169-79 : DOI : 10.1038/nrclinonc.2013.4 En savoir plus
Résumé

In the context of metastatic disease, preclinical models have been used primarily to decipher different steps of the metastatic cascade. Numerous molecular processes operate in these model systems, but none of these has been successfully translated to the clinic. We discuss some of the successes and failures of preclinical models in metastasis research and suggest some of the clues for more clinically relevant research. These potential avenues of research include: the use of adequate statistical methods and well-annotated cohorts in biomarker discovery; an objective assessment of the level of evidence provided by each biomarker; the development of robust molecular or cellular surrogates of metastasis in patients; and original designs for clinical trials.

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Antonio Giordano, Brian L Egleston, David Hajage, Joseph Bland, Gabriel N Hortobagyi, James M Reuben, Jean-Yves Pierga, Massimo Cristofanilli, Francois-Clement Bidard (2013 Jan 24)

Establishment and validation of circulating tumor cell-based prognostic nomograms in first-line metastatic breast cancer patients.

Clinical cancer research : an official journal of the American Association for Cancer Research : 1596-602 : DOI : 10.1158/1078-0432.CCR-12-3137 En savoir plus
Résumé

Circulating tumor cells (CTC) represent a new outcome-associated biomarker independent from known prognostic factors in metastatic breast cancer (MBC). The objective here was to develop and validate nomograms that combined baseline CTC counts and the other prognostic factors to assess the outcome of individual patients starting first-line treatment for MBC.

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S T Ligthart, F-C Bidard, C Decraene, T Bachelot, S Delaloge, E Brain, M Campone, P Viens, J-Y Pierga, L W M M Terstappen (2013 Jan 1)

Unbiased quantitative assessment of Her-2 expression of circulating tumor cells in patients with metastatic and non-metastatic breast cancer.

Annals of oncology : official journal of the European Society for Medical Oncology / ESMO : 1231-8 : DOI : 10.1093/annonc/mds625 En savoir plus
Résumé

Background Circulating tumor cells (CTCs) can provide the basis for a liquid biopsy and may guide the use of targeted therapies. We report on unbiased quantification of Her-2 protein expression of CTCs. Patients and methods Her-2 assessment of CTCs was carried out using the CellSearch(®) system in 103 metastatic (M1) and 88 non-metastatic (M0) breast-cancer patients. Expression of Her-2 on CTCs was determined by a manual review and an automated algorithm using Her-2- fluorescein isothiocyanate (FITC) fluorescence of leukocytes to determine the Her-2-expression threshold in each sample. Results Her-2 expression of CTCs varied greatly within and among patients compared with Her-2 expression of leukocytes. In M1 patients, a threshold of 75% of Her-2 positive CTCs in patients with ≥5 CTCs was set. Applying this threshold, 9% of M1 patients with Her-2-negative primary tumors had Her-2-positive CTC status and 29% of M1 patients with Her-2-positive primary tumors had Her-2-negative CTC status. No Her-2 discrepancy was observed between CTCs and primary tumors in M0 patients. Conclusions Our findings demonstrate that Her-2 expression is heterogeneous among CTCs within each patient. We show the feasibility of unbiased quantitative and reproducible assessment of treatment targets on CTCs, opening a path towards personalized treatment.

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Année de publication : 2012

François-Clément Bidard, Tanja Fehm, Michail Ignatiadis, Jeffrey B Smerage, Catherine Alix-Panabières, Wolfgang Janni, Carlo Messina, Costanza Paoletti, Volkmar Müller, Daniel F Hayes, Martine Piccart, Jean-Yves Pierga (2012 Nov 7)

Clinical application of circulating tumor cells in breast cancer: overview of the current interventional trials.

Cancer metastasis reviews : 179-88 : DOI : 10.1007/s10555-012-9398-0 En savoir plus
Résumé

In 2004, circulating tumor cells (CTC) enumeration by the CellSearch® technique at baseline and during treatment was reported to be associated with prognosis in metastatic breast cancer patients. In 2008, the first evidence of the impact of CTC detection by this technique on survival of cM0(i+) patients were reported. These findings were confirmed by other non-interventional studies, whereas CTC were also investigated as a surrogate for tumor biology, mainly for HER2 expression/amplification. The aim of this report is to present the current prospective large interventional studies that have been specifically designed to demonstrate that CTC enumeration/characterization may improve the management of breast cancer patients: STIC CTC METABREAST (France) and Endocrine Therapy Index (USA) assess the CTC-guided hormone therapy vs chemotherapy decision in M1 patients; SWOG0500 (USA) and CirCe01 (France) assess the CTC count changes during treatment in metastatic patients; DETECT III (M1 patients, Germany) and Treat CTC (cM0(i+) patients, European Organization for Research and Treatment of Cancer/Breast International Group) assess the use of anti-HER2 treatments in HER2-negative breast cancer patients selected on the basis of CTC detection/characterization. These trials have different designs in various patient populations but are expected to be the pivotal trials for CTC implementation in the routine management of breast cancer patients.

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Maura Campitelli, Emmanuelle Jeannot, Martine Peter, Emmanuelle Lappartient, Stéphanie Saada, Anne de la Rochefordière, Virginie Fourchotte, Séverine Alran, Peter Petrow, Paul Cottu, Jean-Yves Pierga, Olivier Lantz, Jérôme Couturier, Xavier Sastre-Garau (2012 Sep 1)

Human papillomavirus mutational insertion: specific marker of circulating tumor DNA in cervical cancer patients.

PloS one : e43393 : DOI : 10.1371/journal.pone.0043393 En savoir plus
Résumé

In most cases of cervical cancers, HPV DNA is integrated into the genome of carcinoma cells. This mutational insertion constitutes a highly specific molecular marker of tumor DNA for every patient. Circulating tumor DNA (ctDNA) is an emerging marker of tumor dynamics which detection requires specific molecular motif. To determine whether the sequence of the cell-viral junction could be used in clinical practice as a specific marker of ctDNA, we analyzed a series of cervical cancer patient serums.

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Julien Autebert, Benoit Coudert, François-Clément Bidard, Jean-Yves Pierga, Stéphanie Descroix, Laurent Malaquin, Jean-Louis Viovy (2012 Jul 17)

Microfluidic: an innovative tool for efficient cell sorting.

Methods (San Diego, Calif.) : 297-307 : DOI : 10.1016/j.ymeth.2012.07.002 En savoir plus
Résumé

At first mostly dedicated to molecular analysis, microfluidic systems are rapidly expanding their range of applications towards cell biology, thanks to their ability to control the mechanical, biological and fluidic environment at the scale of the cells. A number of new concepts based on microfluidics were indeed proposed in the last ten years for cell sorting. For many of these concepts, progress remains to be done regarding automation, standardization, or throughput, but it is now clear that microfluidics will have a major contribution to the field, from fundamental research to point-of-care diagnosis. We present here an overview of cells sorting in microfluidics, with an emphasis on circulating tumor cells. Sorting principles are classified in two main categories, methods based on physical properties of the cells, such as size, deformability, electric or optical properties, and methods based on biomolecular properties, notably specific surface antigens. We document potential applications, discuss the main advantages and limitations of different approaches, and tentatively outline the main remaining challenges in this fast evolving field.

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Hélène Vegas, Thierry André, François-Clément Bidard, François-Régis Ferrand, Florence Huguet, Pascale Mariani, Jean-Yves Pierga (2012 Apr 26)

[Disseminated and circulating tumor cells in gastrointestinal oncology].

Bulletin du cancer : 535-44 : DOI : 10.1684/bdc.2012.1581 En savoir plus
Résumé

Circulating (CTC) and disseminated tumor cells (DTC) represent two different steps of the metastatic process. As with other types of cancer, the recent development of techniques for the detection of CTC and DTC respectively in the blood and bone marrow of patients generated many results in digestive cancers. However, the interpretation of these results and of the prognostic value of CTC/DTC is often limited by the small cohort size and the heterogeneity of detection methods. The aim of this article is to review the different results and their clinical impact, and discuss the possible use of CTC and DTC as new biomarkers. First of all, it is important to take into account the variability of epithelial markers used for the initial stage of immunoselection of CTC/DTC as well as that of molecular or cytological markers used for the second stage of detection. In esophageal, gastric, pancreatic and hepatocellular carcinomas, and in the ileal and pancreatic neuroendocrine tumors, some studies showed a correlation between the detection of CTC and/or DTC and a clinical pejorative course, whether these tumors were at localized or metastatic stages. On colorectal cancer in the adjuvant setting, a recent meta-analysis showed an association between the detection of CTC in peripheral blood and disease-free survival or overall survival. These results are consistent with those of a study that identified detection of CTC as a prognostic factor for relapse in stage II. This last study concluded that it was necessary to achieve long-term evaluation of CTC as a biomarker to guide the decisions of chemotherapy for stage II. In metastatic colorectal cancer, the FDA approved in 2007 the use of pretherapeutic levels of CTC and its variations per-treatment, determined by CellSearch(®) technology, as a tool in treatments management. However, the modalities of this monitoring have to be specified and clinical benefit or the cost-effectiveness of a treatment based on this new biomarker has to be evaluated. Finally, the qualitative and quantitative monitoring of CTC could be a non-invasive tool to monitor changes in tumor biology throughout the disease, and thereby improve the understanding of the processes of dissemination and therapeutic resistance.

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Jean-Yves Pierga, Thierry Petit, Thierry Delozier, Jean-Marc Ferrero, Mario Campone, Joseph Gligorov, Florence Lerebours, Henri Roché, Thomas Bachelot, Emmanuelle Charafe-Jauffret, Maria Pavlyuk, Sandrine Kraemer, François-Clément Bidard, Patrice Viens (2012 Mar 2)

Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study.

The Lancet. Oncology : 375-84 : DOI : 10.1016/S1470-2045(12)70049-9 En savoir plus
Résumé

Bevacizumab and trastuzumab are efficacious for treatment of advanced or HER2-positive metastatic breast cancer; however, few data exist for this regimen in inflammatory breast cancer. In our phase 2 trial, we aimed to assess efficacy and safety of neoadjuvant bevacizumab combined with trastuzumab and chemotherapy in patients with primary HER2-positive inflammatory breast cancer.

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François-Clément Bidard, David Hajage, Thomas Bachelot, Suzette Delaloge, Etienne Brain, Mario Campone, Paul Cottu, Philippe Beuzeboc, Emilie Rolland, Claire Mathiot, Jean-Yves Pierga (2012 Feb 15)

Assessment of circulating tumor cells and serum markers for progression-free survival prediction in metastatic breast cancer: a prospective observational study.

Breast cancer research : BCR : R29 En savoir plus
Résumé

Circulating tumor cells (CTC) have been recently proposed as a new dynamic blood marker whose positivity at baseline is a prognostic factor and whose changes under treatment are correlated with progression-free survival (PFS) in metastatic breast cancer patients. However, serum marker levels are also used for the same purpose, and no clear comparison has been reported to date.

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Année de publication : 2011

Ciprian Chira, Julian Jacob, Najib Derhem, Marc A Bollet, François Campana, Virginie Marchand, Jean-Yves Pierga, Alain Fourquet, Youlia M Kirova (2011 Jun 7)

Preliminary experience of whole-brain radiation therapy (WBRT) in breast cancer patients with brain metastases previously treated with bevacizumab-based chemotherapy.

Journal of neuro-oncology : 401-8 : DOI : 10.1007/s11060-011-0607-4 En savoir plus
Résumé

We report our experience of bevacizumab-based chemotherapy (BBCT) followed by whole-brain radiation therapy (WBRT) for breast cancer (BC) patients (pts) with inoperable brain metastases (BM) or who refused surgery. This is a retrospective study of seven metastatic BC pts treated at the Institut Curie with at least one course of BBCT before WBRT, with a delay of ≤ 12 months between the two treatments. Toxicity was scored according to the common terminology criteria for adverse events (v4. 2010). Median age was 56 years (41-65). Median follow-up was 5.9 months (0.4-24.6). The median dose of bevacizumab was 10 mg/kg. Median number of cycles BBCT was six (5-17). Different chemotherapy regimens were used, the most common combination was paclitaxel-bevacizumab. WBRT was delivered in ten fractions, five fractions/week, for two weeks, to a total of 30 Gy. One pt underwent stereotactic radio surgery (SRS) after WBRT. No pt received BBCT during RT. Most common reported side-effects were nausea (n = 4), headache (n = 3), vomiting (n = 1), and vertigo (n = 3). All pts had mild or moderate grade ≤ 2 neurologic toxicity. There were no radiological signs of necrosis or cerebral ischemia. BBCT before WBRT was not associated with severe brain toxicity. Because of the limited number of pts, the different BBCT regimens, and important delays between treatments, these results must be confirmed prospectively.

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Hélène Petithuguenin Gauthier, Marie-Noëlle Guilhaume, François-Clément Bidard, Jean-Yves Pierga, Véronique Girre, Paul-Henri Cottu, Valérie Laurence, Alain Livartowski, Laurent Mignot, Véronique Dieras (2011 May 6)

[Survival of breast cancers patients with meningeal carcinoma].

Bulletin du cancer : 391-8 : DOI : 10.1684/bdc.2011.1340 En savoir plus
Résumé

Among all solid tumors breast cancer is the most common cause of meningeal carcinomatosis (MC). The purpose of this study was to analyze clinical and biological responses as well as overall survival in MC patients (pts) of breast primary treated with intrathecal methotrexate (MTX).

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Véronique Diéras, Jean-Yves Pierga (2011 Apr 30)

[Brain metastasis of breast tumors and blood brain barrier].

Bulletin du cancer : 385-9 : DOI : 10.1684/bdc.2011.1336 En savoir plus
Résumé

Brain metastases are prevalent in solid tumours and lymphomas. They are associated with poor survival. The brain is regarded as a sanctuary site for metastatic tumour cells where they exist partially protected from drugs by the blood brain barrier. Amongst the different molecular sub-types of breast cancer, HER2 positive tumours and triple negative tumours exhibit the highest incidence of brain metastasis. Specific strategies are needed to fight brain metastatic disease. Preclinical models for brain metastasis have been developed, yielding mechanistic molecular knowledge and new therapeutic approaches.

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Christophe Le Tourneau, Sarah Dettwiler, Philippe Beuzeboc, Séverine Alran, Valérie Laurence, Jean-Yves Pierga, Paul Fréneaux, Brigitte Sigal-Zafrani, Véronique Diéras, Anne Vincent-Salomon (2011 Mar 2)

Pathologic response to short intensified taxane-free neoadjuvant chemotherapy in patients with highly proliferative operable breast cancer.

American journal of clinical oncology : 242-6 : DOI : 10.1097/COC.0b013e318209d34c En savoir plus
Résumé

Breast cancer treatment relies on 3 major phenotypical subtypes, including the triple-negative (TN), HER2-positive, and hormone receptor-positive (estrogen receptor/progesterone receptor) ones. We retrospectively determined the clinical and pathologic response rates to intensified taxane-free neoadjuvant chemotherapy according to these phenotypical classes in a series of patients with highly proliferative operable breast cancer, and examined the patterns of recurrence.

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Année de publication : 2010

Cyrus Chargari, Hind Riahi Idrissi, Jean-Yves Pierga, Marc A Bollet, Véronique Diéras, François Campana, Paul Cottu, Alain Fourquet, Youlia M Kirova (2010 Oct 12)

Preliminary results of whole brain radiotherapy with concurrent trastuzumab for treatment of brain metastases in breast cancer patients.

International journal of radiation oncology, biology, physics : 631-6 : DOI : 10.1016/j.ijrobp.2010.06.057 En savoir plus
Résumé

To assess the use of trastuzumab concurrently with whole brain radiotherapy (WBRT) for patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer.

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