دورية أكاديمية
Biological and clinical features of triple negative Invasive Lobular Carcinomas of the breast. Clinical outcome and actionable molecular alterations
| العنوان: | Biological and clinical features of triple negative Invasive Lobular Carcinomas of the breast. Clinical outcome and actionable molecular alterations |
|---|---|
| المؤلفون: | Conforti, Fabio, Pala, Laura, Pagan, Eleonora, Rocco, Elena Guerini, Bagnardi, Vincenzo, Montagna, Emilia, Peruzzotti, Giulia, De Pas, Tommaso, Fumagalli, Caterina, Pileggi, Silvana, Pesenti, Chiara, Marchini, Sergio, Corso, Giovanni, Marchio’, Caterina, Sapino, Anna, Graffeo, Rossella, Collet, Laetitia, Aftimos, Philippe, Sotiriou, Christos, Piccart, Martine, Gelber, Richard D., Viale, Giuseppe, Colleoni, Marco, Goldhirsch, Aron |
| المساهمون: | 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, Goldhirsch, A |
| بيانات النشر: | Churchill Livingstone GB |
| سنة النشر: | 2021 |
| المجموعة: | Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
| مصطلحات موضوعية: | Androgen receptor, ERBB2 gene mutation, HER2/PI3K/AKT pathway, Luminal androgen receptor subtype, Triple negative invasive lobular carcinoma |
| الوصف: | 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<0.05), there were ErbB-signaling and DNA-damage-response pathways. Conclusions: TN-ILCs are rare tumors with poor prognosis. Their specific biological features require newly defined targeted therapeutic strategies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/34217971; info:eu-repo/semantics/altIdentifier/wos/WOS:000696705600013; volume:59; issue:October 2021; firstpage:94; lastpage:101; numberofpages:8; journal:THE BREAST; http://hdl.handle.net/10281/319650Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85108955655 |
| DOI: | 10.1016/j.breast.2021.06.011 |
| الإتاحة: | https://doi.org/10.1016/j.breast.2021.06.011Test http://hdl.handle.net/10281/319650Test |
| رقم الانضمام: | edsbas.F7DC0E9C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.breast.2021.06.011 |
|---|