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Molecular profilingof hormonereceptor-positive,HER2-negative breastcancers from patientstreated withneoadjuvant endocrinetherapy in theCARMINA 02… Liang XuAdrien BriauxVéronique Becette2018 год

Molecular profiling of hormone receptor-positive, HER2-negative breast cancers from patients treated with neoadjuvant endocrine therapy in the CARMINA 02 trial (UCBG-0609)
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Аннотация: Postmenopausal women with large, hormone receptor (HR)-positive/HER2-negative and low-proliferative breast cancer derived a benefit from neoadjuvant endocrine therapy (NET) in the CARMINA02 trial. This study was designed to correlate gene expression and mutation profiles with both response to NET and prognosis. Gene expression profiling using RNA sequencing was performed in 86 pre-NET and post-NET tumor samples. Targeted next-generation sequencing of 91 candidate breast cancer-associated genes was performed on DNA samples from 89 patients. Molecular data were correlated with radiological response and relapse-free survival. The transcriptional profile of tumors to NET in responders involved immune-associated genes enriched in activated Th1 pathway, which remained unchanged in non-responders. Immune response was confirmed by analysis of tumor-infiltrating lymphocytes (TILs). The percentage of TILs was significantly increased post-NET compared to pre-NET samples in responders (p = 0.0071), but not in non-responders (p = 0.0938). Gene expression revealed that lipid metabolism was the main molecular function related to prognosis, while PPARγ is the most important upstream regulator gene. The most frequently mutated genes were PIK3CA (48.3%), CDH1 (20.2%), PTEN (15.7%), TP53 (10.1%), LAMA2 (10.1%), BRCA2 (9.0%), MAP3K1 (7.9%), ALK (6.7%), INPP4B (6.7%), NCOR1 (6.7%), and NF1 (5.6%). Cell cycle and apoptosis pathway and PIK3CA/AKT/mTOR pathway were altered significantly more frequently in non-responders than in responders (p = 0.0017 and p = 0.0094, respectively). The average number of mutations per sample was significantly higher in endocrine-resistant tumors (2.88 vs. 1.64, p = 0.03), but no difference was observed in terms of prognosis. ESR1 hotspot mutations were detected in 3.4% of treatment-naive tumors. The Th1-related immune system and lipid metabolism appear to play key roles in the response to endocrine therapy and prognosis in HR-positive/HER2-negative breast cancer. Deleterious somatic mutations in the cell cycle and apoptosis pathway and PIK3CA/AKT/mTOR pathway may be relevant for clinical management. This trial is registered with ClinicalTrials.gov ( NCT00629616 ) on March 6, 2008, retrospectively registered.
Год издания: 2018
Авторы: Liang Xu, Adrien Briaux, Véronique Becette, Camille Benoist, Anaïs Boulai, Walid Chemlali, Anne Schnitzler, Sylvain Baulande, Sofía Rivera, Marie‐Ange Mouret‐Reynier, Laurence Vénat-Bouvet, T. de La Motte Rouge, Jérôme Lemonnier, Florence Lerebours, Céline Callens
Издательство: BioMed Central
Источник: Journal of Hematology & Oncology
Ключевые слова: Cancer Immunotherapy and Biomarkers, Cancer Cells and Metastasis, Ferroptosis and cancer prognosis
Другие ссылки: Journal of Hematology & Oncology (PDF)
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HAL (Le Centre pour la Communication Scientifique Directe) (HTML)
DOAJ (DOAJ: Directory of Open Access Journals) (HTML)
HAL (Le Centre pour la Communication Scientifique Directe) (HTML)
PubMed Central (HTML)
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