351O - Genomic and immune characterization of metastatic breast cancer (mBC): And ancillary study of the SAFIR01 & MOSCATO trials

Date 28 September 2014
Event ESMO 2014
Session Breast cancer, metastatic
Topics Breast Cancer, Metastatic
Pathology/Molecular Biology
Presenter Fabrice André
Citation Annals of Oncology (2014) 25 (suppl_4): iv116-iv136. 10.1093/annonc/mdu329
Authors M. Arnedos1, T. Filleron2, M.V. Dieci3, J. Adam4, P.B. Robbins5, S. Loi6, M. Campone7, H. Bonnefoi8, V. Dieras9, F. Dalenc10, M. Jimenez11, J. Soria12, C. Lefebvre13, F. André1, T. Bachelot14, M. Lacroix-Triki15
  • 1Department Of Medicine; Breast Unit, Gustave Roussy, 94805 - Villejuif/FR
  • 2Biostatistics, Institut Claudius Regards, Toulouse/FR
  • 3Medical Oncology 2 And Department Ofsurgery, Oncology And Gastroenterology, Istituto Oncologico Veneto IRCCS and University of Padova, Padova/IT
  • 4Pathology, Gustave Roussy, Villejuif/FR
  • 5Oncology, MedImmune, LLC, Gaithersburg/US
  • 6Division Of Cancer Medicine, Peter MacCallum Cancer Centre, 3002 - Melbourne/AU
  • 7Medical Oncology, Institut de Cancérologie de l’Ouest - René Gauducheau, Herblain/FR
  • 8Medical Oncology, Institute Bergonié, Bordeaux/FR
  • 9Department Of Medical Oncology, Clinical Trial Unit, Institut Curie, 75005 - Paris/FR
  • 10Service D'oncologie Médicale, Institut Claudius Regaud, Toulouse/FR
  • 11R&d, Unicancer, 75013 - Paris/FR
  • 12Innovative Therapeutics And Early Drug Development, Institut Gustave Roussy, 94800 - villejuif/FR
  • 13Inserm Unit U981, Gustave Roussy, 94805 - Villejuif/FR
  • 14Medical Oncology, Centre Léon Bérard, 69373 - Lyon/FR
  • 15Oncology Department, Institut Claudius Regaud, 31052 - Toulouse/FR

Abstract

Aim

So far, little is known about immune and genomic landscape in metastatic breast cancer (mBC).

Methods

Patients were retrospectively identified from SAFIR01 and MOSCATO studies that performed molecular screening from a biopsy of a metastatic lesion. Whole exome sequencing (WES) was performed using Hi-Seq technology. Coverage was 50x and 100x for normal and tumoral tissue respectively. Bioinformatic analyses reported mutations and copy number alterations. Immune characterisation was determined by the presence of intratumoral and stromal TILs with PD1 and PDL1 expression assessed by IHC (internal protocol, Medimmune). We correlated tumor characteristics and immune and genomics data.

Results

280 samples were stained for immune analyses. Using a 50% cut-off, few tumors presented intratumoral (n = 3/244, 1%) and stromal (n = 11/244, 5%) TILs. This rate was significantly higher in HER2+ tumors (stromal TIL, 16%; p = 0.0002). Positivity for PD1 (n = 14/252, 5%) and PDL1 (n = 7/255, 3%) were rare, compared to reported in other tumor types. A trend towards higher PDL1 was observed in HER2+ mBC (8.3%; p = 0.0653). Ninety-three samples were analysed for WES with 17 genes found mutated in >3 samples (p < 0.05). Except for PIK3CA, p53 and AKT1, these genes were mutated in <2% of samples in TCGA analyses of primary tumors and include NAV3 (n = 5), FRAS1 (n = 7), PI4KA (n = 5), PALB2 (n = 4), SCAPER (n = 4), PRKCB (n = 4), CACNA1S (n = 4), TSC1 (n = 4), GALC (n = 4), NPAP1 (n = 4), PHACTR3 (n = 4). When analysing genes specifically mutated in metastases, an enrichment in pathways involved in MAPK (FDR = 0.0035), ER signalling (0.0004), lipids metabolism (0.0001) and GNRH signalling (FDR = 0.00018) was observed

Conclusions

This is the first study that assesses both immune and genomic landscapes in mBC. We observed that mBC dramatically differs from primary tumors, and is enriched in genes potentially involved in resistance mechanisms (ESR1, TSC1) or migration process (FRAS1, SCAPER). TILs, PD1, PDL1 are at very low frequency in metastatic lesions, except for Her2 + ++ mBC. Our results suggest that other immune suppressor networks are involved in mBC. Therefore, CD73, CD39 and FoxP3 are being analysed and will be presented.

Disclosure

P.B. Robbins: Salary from Medimmune, Inc. All other authors have declared no conflicts of interest.