by Fabio Conforti, Laura Pala, Eleonora Pagan, Elena Guerini
Rocco, Vincenzo Bagnardi, Emilia Montagna, Giulia Peruzzotti, Tommaso De Pas,
Caterina Fumagalli, Silvana Pileggi, Chiara Pesenti, Sergio Marchini, Giovanni
Corso, Caterina Marchio’, Anna Sapino, Rossella Graffeo, Laetitia Collet,
Philippe Aftimos, Christos Sotiriou, Martine Piccart, Richard D. Gelber,
Giuseppe Viale, Marco Colleoni, Aron Goldhirsch
The Breast: VOLUME 59, P94-101, OCTOBER 01, 2021
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
