Integrated immuno-genomic analyses in early breast cancer: Results from the Scandinavian breast group 2004-1 (SBG-2004-1) randomized phase II trial

Läs om studien som presenteras av postdoc Ioannis Zerdes och ass prof Theodore Foukakis med kollegor på Karolinska institutet. Studien visar två potentiellt möjliga tekniker för DNA CNAs och immunprofilering på arkiverade FFPE bröstcancerprover. 

What is the background and aim your study?

In this translational proof-of-principle study, we aimed to characterize the genomic alterations, immune cell abundance patterns and their interaction in the phase II Scandinavian Breast Group 2004-1 early breast cancer adjuvant chemotherapy trial, using two recently established methods.

You have evaluated two newly developed techniques, one for multiplexed fluorescent immunohistochemistry (mfIHC), and one for genome sequencing (CUTseq), on tumor samples from the SBG-2004-1 trial. Why were you interested in working with these methods?

To follow up on our previous work evaluating tumor-immune interactions, we applied the automated digital multiplex fluorescent IHC, enabling the identification and quantitation of multiple immune markers at a spatial tissue context, in situ. The versatile CUTseq method enabled preparation of multiplexed DNA sequencing libraries and copy-number alterations (CNA) profiling from low-input archival FFPE samples at a high resolution, in a cost-effective manner (in collaboration with Assistant Professor Nicola Crosetto, KI/SciLife Laboratory who developed the method).

What results did you obtain?

Different immune cell patterns were recognized, with CD4+ T-cells to be the most abundant cell subpopulation in both tumor and stromal compartments and also mostly expressed the PD-L1 and PD-1 checkpoint proteins. Regarding CNA profiles, MYC and FGFR1 were the most frequently altered cancer-associated genes, while ERBB2, PIK3CA amplification as well as TP53 and PTEN deletion were also commonly observed. Of note, CNA burden (i.e the percentage of the genome either amplified or deleted) was inversely correlated with immune infiltration, as revealed in combined analyses.

What are your conclusions, and how would you like to apply these results in the future?

We demonstrated the feasibility and potential of two newly developed techniques for CNA and immune profiling from archival FFPE patient samples and also provided a link between genomic alterations and immune response in early breast cancer. Further application of these methods in the continuation large international multicentric phase III PANTHER adjuvant breast cancer trial will shed light on prognostic and predictive implications of immunogenomic patterns and ultimately may pave the way for improving patient selection for immunotherapy.

 

 

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PP-IBR-SWE-0426, Dec 2020