Les cancers du sein agressifs : conséquences de la ménopause chimio-induite chez les femmes jeunes atteintes d'un cancer du sein non métastatique et facteurs pronostiques de la rechute du cancer du sein triple négatif

Abstract : Breast cancer is the most common cancer among women and despite a decline in mortality in recent years, due to early detection and better treatment management, it remains a major public health issue. Breast cancer mortality has been found to be higher in the case of aggressive or poor prognostic cancers such as breast cancer in young women and the triple negative subtype of breast cancer (TNBC).This PhD focuses on these two types of breast cancer and aims to study the consequences of chemotherapy-induced menopause (CIM) in young women with non metastatic breast cancer and evaluate the prognostic factors of TNBC relapse. One of the aspect of my PhD is based on the clinical study MENOCOR. The main objective of this study is to evaluate the impact of CIM on the quality of life (QoL) of young women with non metastatic breast cancer. The incidence of CIM and the study of hormonal variations are also a part of the secondary objectives. As a part of this PhD work, the interim analysis planned in the study protocol was conducted on 59 patients with a follow-up of 18 months post-chemotherapy. These first results tend to show a QoL decrease, evaluted by the QLQ-BR23, in menopausal women vs non menopausal women (p=0.17). At this stage of the trial, the QLQ-BR23 seems to be more appropriate than the QLQ-C30 to evaluate QoL. We also underline the possible prediction of CIM by the inital AMH level and age. Thus, these results should be compared to the final analysis and we expect that with a greater power (240 patients and a follow-up of 30 months post-chemotherapy) the QoL results will reach significance.The second axis consists of a database on TNBC. This retrospective study follows the work carried out in Jean PERRIN Cancer Center and aims to evaluate dynamics and pronostic factors of TNBC relapse. The analysis showed that the main pronostic factors are the node metastasis, the presence of emboli and the tumor size. The variability of response to chemotherapy (pCR to chemoresistance) and the diversity of relapses (early relapse (<1 year), standard relapse (1 to 5 years) and late relpase (> 5 years)) confirmed the heterogeneity of TNBC highlighting the need to continue the research of new biomarkers. In conclusion, these results open up many research perspectives. We plan to compare the final results of the MENOCOR study with those of the interim analysis presented in this PhD work. At the end of the study, we expect to have a better knowledge of CIM, its impact on QoL and the role of AMH in predicting menopause. Regarding the TNBC, it is planned to conduct another larger retrospective study focused in hematologic parameters evaluating the role of hematologic and genetic parameters. Depending on the results, a prospective study could be promoted in order to evaluate the role of tumoral micro-environment, and hematologic and genetic parameters in TNBC relapse.
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Judith Passildas Jahanmohan. Les cancers du sein agressifs : conséquences de la ménopause chimio-induite chez les femmes jeunes atteintes d'un cancer du sein non métastatique et facteurs pronostiques de la rechute du cancer du sein triple négatif. Médecine humaine et pathologie. Université Clermont Auvergne, 2019. Français. ⟨NNT : 2019CLFAS003⟩. ⟨tel-02292709⟩

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