Pour quelles patientes peut-on envisager une désescalade dans la prise en charge des carcinomes canalaires in situ ?

International audienceDuctal carcinomas in situ (DCIS) of the breast account for 85% to 90% of breast cancer in situ. Current recommendations for the management of DCIS in France are based on surgical excision of the lesions, lumpectomy in healthy margins (margins of excision≥2mm) or mastectomy in case of extensive lesions. Radiation therapy is recommended after conservative surgical treatment. However, it seems relevant for some patients to discuss the benefit of a therapeutic de-escalation. Indeed, it has been reported that radiotherapy has no major impact on overall survival and that its interest could be discussed in the low-risk situations of invasive recurrence for which surgery alone could be sufficient, subject to sufficient margins. These questions call for the precise definition of low risk populations and to clarify the importance of taking into account decision support tools and new molecular markers. The place of scores like that of the University of Southern California - Van Nuys, and that of genomic tests such as the Oncotype test© DX DCIS (DCIS score) need to be specified. The expected results of several prospective studies could go in the direction of a significant therapeutic de-escalation for the management of DCIS in the years to come. In the meantime, however, it is advisable to remain cautious and the inclusion of patients in clinical trials should be favored.Les carcinomes canalaires in situ (CCIS) du sein représentent 85 % à 90 % des cancers in situ du sein. Les recommandations actuelles pour la prise en charge des CCIS en France, publiée en 2015 par l’Institut National du Cancer (INCa), reposent sur l’exérèse chirurgicale des lésions, par une tumorectomie en berges saines (marges d’exérèse ≥ 2 mm) ou par une mastectomie en cas de lésions étendue. La radiothérapie est recommandée après traitement chirurgical conservateur. Pour certaines patientes, une désescalade thérapeutique parait envisageable aux vues des données de la littérature. Ainsi, il a été rapporté que la radiothérapie n’a pas d’impact majeur sur la survie globale et que son intérêt pourrait être discuté dans les situations les moins à risque de récidive invasive pour lesquelles la chirurgie seule pourrait être suffisante, sous réserve de marges suffisantes. Ces interrogations imposent la définition précise de populations à bas risque et de préciser l’intérêt de la prise en compte des outils d’aide à la décision et des nouveaux marqueurs moléculaires. La place de scores comme celui de l’Université de Californie du Sud – Van Nuys, et celle des tests génomiques comme le test Oncotype© DX DCIS (DCIS score) doivent être précisées. Les résultats attendus de plusieurs études prospectives en cours d’inclusion pourraient aller dans le sens d’une désescalade thérapeutique significative pour la prise en charge adjuvante des CCIS dans les années à venir. Il convient toutefois en attendant ces résultats de rester prudents et de privilégier l’inclusion des patientes dans des essais thérapeutiques

191 PLASMA LEVELS OF D-TRP-6-LH-RH (DECAPEPTYL) AFTER INTRAMUSCULAR INJECTION OF LONG-ACTING MICROCAPSULES IN CHILDREN TREATED FOR PRECOCIOUS PUBERTY (PP)

The efficacy of periodic administration of Decapeptyl microcapsules upon symptoms of PP has been previously reported (Roger et al., ESPE meeting 1984, abstract 22). A sensitive radioimmuno assay of the analogue was developped using an antiserum raised in rabbit which exhibited unsignificant cross reactivity with native LH-RH or LH-RH fragments (Mason-Garcia et al.,Proc.Natl. Acad. Sci., USA, in press). Iodinated D-Trp-6-LH-RH was used as a tracer. Fifty μl antiserum diluted at 1/2500 , 50 μl tracer, 100 μl standard (or unknown plasma), 100 μl plasma pool (or phosphate buffer 0.01 M, pH 7.5) were incubated for 24 h. Free and bound were separated by PEG. NSB of the plasma pool and of 40 different child samples were respectively 6.2± 0.4 and 6.3± 0.4% (mean±SD). Bo was 20%. Intraassay CV were 12 and 7% for mean plasma levels of 100 and 370 pg/ml respectively. The detec tion limit was 57 pg/ml. Five children received intramuscularly (IM) on days 1, 21 and every 28 days thereafter, 1.5 mg Decapeptyl microcapsules. Plasma levels were on days 3, 7, 14, and 21 (pg/ml, mean±SEM) 312±57, 242±65, 145±78 and 171±87. Decapeptyl was undetectable in most of samples on day 28 after injection. This study demonstrates that significant Decapeptyl levels are maintained for at least 21 days after a single IM injection

Treatment of male and female precocious puberty (PP) by monthly injections of a continuous release preparation of D-Trp-6-LH-RH

Successful treatment of PP by daily subcutaneous (SC) administration of the LH-RH agonist D-Trp-6-LH-RH (Trp6) was reported (Kauli et al., ESPE 1983). After demonstration of its efficiency and innocuity in dogs, a long acting preparation designed for releasing continuously 100 μg Trp6 per 24 h, was given intramuscularly to 3 boys and 3 girls with PP, aged 3 to 8 years. 3 mg Trp6 were injected every 28 days, cyproterone acetate being associated during the first week. In boys testosterone levels (ng/ml) decreased from 2.2-5 to 0.1-0.2 within 2 months. Testis volume was unaffected in 1, decreased slighty in 2. In girls estradiol levels (pg/ml) decreased from 40-100 to 0-40 within 2 months and in a menstruating girl genital bleeding desappeared after 1 month. Breast enlargement was reduced in all. In all children, the gonadotropin responses to LH-RH were suppressed and the inhibition of gonadal secretion persisted after 6 months of treatment. The data demonstrate the ability of long acting Trp6 to suppress gonadal secretion by a monthly injection in children with PP