51. Biological and clinical features of triple negative Invasive Lobular Carcinomas of the breast. Clinical outcome and actionable molecular alterations☆
- Author
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Eleonora Pagan, Richard D. Gelber, Fabio Conforti, Christos Sotiriou, Silvana Pileggi, Anna Sapino, Caterina Marchiò, Philippe Aftimos, Rossella Graffeo, Chiara Pesenti, Laetitia Collet, Giulia Peruzzotti, Vincenzo Bagnardi, Giovanni Corso, Marco Colleoni, Tommaso De Pas, Giuseppe Viale, Laura Pala, Martine Piccart, Caterina Fumagalli, Elena Guerini Rocco, Emilia Montagna, Sergio Marchini, Aron Goldhirsch, Conforti, F, Pala, L, Pagan, E, Rocco, E, Bagnardi, V, Montagna, E, Peruzzotti, G, De Pas, T, Fumagalli, C, Pileggi, S, Pesenti, C, Marchini, S, Corso, G, Marchio’, C, Sapino, A, Graffeo, R, Collet, L, Aftimos, P, Sotiriou, C, Piccart, M, Gelber, R, Viale, G, Colleoni, M, and Goldhirsch, A
- Subjects
Oncology ,medicine.medical_specialty ,Poor prognosis ,ERBB2 gene mutation ,Receptor, ErbB-2 ,ERBB2 gene mutations ,Breast Neoplasms ,medicine.disease_cause ,Internal medicine ,medicine ,Biomarkers, Tumor ,Mutational status ,Humans ,Breast ,skin and connective tissue diseases ,Triple negative ,Gene ,RC254-282 ,Mutation ,Triple negative invasive lobular carcinoma ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Médecine pathologie humaine ,General Medicine ,Androgen receptor ,HER2/PI3K/AKT pathway ,Luminal androgen receptor subtype ,Sciences bio-médicales et agricoles ,Prognosis ,Cancérologie ,body regions ,Carcinoma, Lobular ,Cohort ,Surgery ,Original Article ,Female ,business - Abstract
Background We report here for the first time, a comprehensive characterization of biological and clinical features of early-stage triple negative Invasive Lobular Carcinomas(TN-ILCs) Methods We analyzed all consecutive patients with early-stage TN-ILC operated at two reference cancer-centers between 1994 and 2012. Primary objective was to assess the invasive disease-free survival(iDFS). Co-primary objective was to assess biological features of TN-ILCs, including molecular intrinsic subtypes based on PAM-50 assay, expression of androgen receptor (AR) and mutational status of ERBB2-gene. Additionally, DNA mutational status of an independent cohort of 45 TN-ILCs from three databases were analyzed, to confirm mutations in ERBB2-gene and to identify other recurrently mutated genes. Results Among 4152 ILCs, 74(1.8%) were TN and were analyzed. The iDFS at 5 and 10 years of FUP were 50.4%(95%CI,38.0–61.6) and 37.2%(95%CI,25.5–48.8), respectively. The molecular subtype was defined through PAM50-classifier for 31 out of 74 TN-ILCs: 48% were Luminal-A(15/31), 3% luminal-B(1/31), 32% HER2-enriched (10/31), and only 16% basal-like(5/31). Luminal tumors expressed AR more frequently than non-luminal tumors (AR≥1% in 94% of luminal tumors versus 53% in non-luminal tumors; p-value = 0.001). 20% of TN-ILCs analyzed(7/35), harbored a pathogenetic and actionable mutation in the ERBB2-gene. Analysis of the independent cohort of 45 TN-ILCs from three different databases, confirmed similar percentage of pathogenetic and actionable mutations in ERBB2-gene(20%; 9/45). Among the top 10 molecular pathways significantly enriched for recurrently mutated genes in TN-ILCs(FDR, Highlights • Triple-negative ILCs are distinct from both TN-IDCs and endocrine-responsive ILC. • TN-ILCs are enriched for actionable mutations in ErbB2 gene and DNA Damage Response genes. • The Luminal Androgen Receptor (LAR) is the most prevalent subtype in TN-ILCs.
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- 2021