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ABSTRACT: Aggressive fibromatosis (AF) is a monoclonal proliferative disease but does not metastasize and does not dedifferentiate to a high-grade malignancy in case of recurrence. Biopsy is usually necessary to confirm the diagnosis. A hallmark is its apparent unpredictable clinical course producing a large heterogeneity even with an indistinguishable morphology. Additional studies of the molecular determinants of desmoid behavior are needed to guide selection of the various therapeutic modalities. During the last 10 years, the treatment of AF has evolved and the role of routine, aggressive first-line treatment (radiotherapy and surgery) is now debated. If a wait-and-see policy is used at initial presentation, it is observed that >50% of patients will have relatively indolent disease. Aggressive treatments that take their indications from retrospective studies should be re-evaluated in the light of new data. The objective of this article is to propose an algorithm that commences with more conservative approaches before treatments that have associated long-term morbidity, the more aggressive therapies being reserved only for those who really need it.
Annals of Oncology 09/2012; 23 Suppl 10:x158-x166. · 6.43 Impact Factor
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ABSTRACT: Since the discovery of the remarkable efficacy of imatinib in the metastatic GIST, several studies advanced our knowledge on the care of this pathology. In the localized GIST, the efficacy of the adjuvant treatment by imatinib was proved, but the duration, the indication and the management in case of relapse after imatinib are not still consensual. The imatinib is also used in neoadjuvant setting to optimize the quality of resection, the main treatment remaining the maximal tumor resection. In metastatic setting, imatinib remains the standard of care first-line treatment. It must be administered until progress or intolerance. Nevertheless, secondary resistance to imatinib is a substantial problem in routine clinical practice; in second line, sunitinib demonstrated its efficacy. Several inhibitors of tyrosine-kinases are ongoing evaluated in all the therapeutic lines. Clearly, a better knowledge of the molecular profile and the pharmacokinetics underlying the resistance to imatinib as well as the development of a new class of broad-spectrum tyrosine-kinase inhibitors may allow in the near future new individualized therapeutic strategies for GIST patients.
Bulletin du cancer 06/2010; 97(6):723-31. · 0.67 Impact Factor
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J Dômont,
S Salas,
L Lacroix,
V Brouste,
P Saulnier,
P Terrier,
D Ranchère,
A Neuville,
A Leroux,
L Guillou,
R Sciot,
F Collin,
A Dufresne,
J-Y Blay,
A Le Cesne,
J-M Coindre,
S Bonvalot,
J Bénard
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ABSTRACT: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for beta-catenin mutations in a European multicentre series of fibromatosis tumours to relate beta-catenin mutational status to disease outcome.
Direct sequencing of exon 3 beta-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients).
Mutations of beta-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with beta-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in beta-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02).
A high frequency (87%) of beta-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type beta-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.
British Journal of Cancer 03/2010; 102(6):1032-6. · 5.04 Impact Factor
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ABSTRACT: We hypothesized that, among molecular subclasses of breast cancer, p53 status may have a differential predictive value for the efficacy of anthracyclines/alkylating agents-based regimen. We analysed the efficacy of a preoperative combination between 5-fluorouracil, anthracyclines and cyclophosphamide according to both p53 status and molecular classification.
Oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) expression and p53 status were determined by immunohistochemistry in 293 samples from two different centres. A logistic regression model was used for multivariate analysis of predictors for pathological complete response (pCR).
p53 immunostaining (54%) was associated with high grade (P = 0.002) and ER negativity (P = 0.04). p53 was detected in 59% of triple-negative tumours (ER-/PgR-/HER2-, n = 120 patients). In the overall population, pCR (9.6%) was independently predicted by high tumour grade (P = 0.002) and ER/PgR/HER2 triple negativity (P = 0.0004), but not by p53 status (P = 0.12). p53 immunostaining was associated with a trend for a higher rate of pCR in triple-negative tumours [relative risk (RR) = 2.5, 95% confidence interval (CI) = 0.8-7.5, P = 0.09], but not in non-triple-negative tumours (RR = 0.73, 95% CI = 0.16-3.3, P = 0.69).
p53 status may have a different predictive value for efficacy of anthracycline/alkylating agents-based regimen in each molecular subclass, a result which may explain the different results reported in literature.
Annals of Oncology 08/2008; 19(7):1261-5. · 6.43 Impact Factor
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ABSTRACT: L'imatinib mesylate (IM), inhibiteur sélectif des tyrosines kinases BCR-ABL, c-KIT et PDGFR, a ouvert des perspectives considérables
dans le domaine de l'oncologie médicale. L'activité remarquable l'IM dans la LMC a rapidement fait envisager son utilisation
dans d’autres tumeurs. L'IM n'a pour l'instant pas porté ses fruits dans d'autres pathologies tumorales en dehors de quelques
exceptions (chordome, dermatofibrosarcome protuberans, fibromatose, glioblastome...). Pourtant, ce concept reste une voie
à suivre pour la recherche à venir, reposant d'abord sur la connaissance des anomalies moléculaires causales avant d'identifier
de nouvelles thérapeutiques ciblées. Les échecs relatifs, concernant les tumeurs non-GIST, nous montrent bien la complexité
du cancer. La mutation c-KIT n'est malheureusement pas la voie universelle de la tumorigenèse. Cependant, la voie des tyrosines
kinases va très certainement continuer dans les années à venir à nourrir nos espoirs contre le cancer.
Imatinib mesylate (IM), a selective inhibitor of tyrosine kinase, including BCR-ABL, c-Kit and PDGFR, opened considerable
avenues in the field of medical oncology. The unique activity of IM in leptomeningeal carcinomatosis (LMC) quickly made its
use in the treatment of other tumours a possibility. However, outside a few exceptions (chordoma, dermatofibrosarcoma protuberans,
fibromatosis, glioblastoma), IM does not effectively treat other solid tumours. Nevertheless, the concept remains a subject
for future research, focused primarily on causative molecular abnormalities prior to identifying novel targeted therapeutics.
The relative failure in treating non-GIST tumours demonstrates cancer's complexity. Unfortunately, the c-Kit mutation is not
the universal pathway of tumorigenesis. However, tyrosine kinase will certainly continue to feed our hopes for finding new
cancer treatments in the coming years.
Oncologie 01/2006; 8(9):801-807. · 0.17 Impact Factor
