Proteogenomics decodes the evolution of human ipsilateral breast cancer
Journal article, 2023

Ipsilateral breast tumor recurrence (IBTR) is a clinically important event, where an isolated in-breast recurrence is a potentially curable event but associated with an increased risk of distant metastasis and breast cancer death. It remains unclear if IBTRs are associated with molecular changes that can be explored as a resource for precision medicine strategies. Here, we employed proteogenomics to analyze a cohort of 27 primary breast cancers and their matched IBTRs to define proteogenomic determinants of molecular tumor evolution. Our analyses revealed a relationship between hormonal receptors status and proliferation levels resulting in the gain of somatic mutations and copy number. This in turn re-programmed the transcriptome and proteome towards a highly replicating and genomically unstable IBTRs, possibly enhanced by APOBEC3B. In order to investigate the origins of IBTRs, a second analysis that included primaries with no recurrence pinpointed proliferation and immune infiltration as predictive of IBTR. In conclusion, our study shows that breast tumors evolve into different IBTRs depending on hormonal status and proliferation and that immune cell infiltration and Ki-67 are significantly elevated in primary tumors that develop IBTR. These results can serve as a starting point to explore markers to predict IBTR formation and stratify patients for adjuvant therapy.

Author

Tommaso De Marchi

Lund University

Paul Theodor Pyl

Science for Life Laboratory (SciLifeLab)

Martin Sjöström

University of California

Lund University

Susanne Reinsbach

Chalmers, Life Sciences, Systems and Synthetic Biology

Sebastian DiLorenzo

Uppsala University

Björn Nystedt

Uppsala University

Lena Tran

Lund University

Gyula Pekar

Lund University

Fredrik Wärnberg

University of Gothenburg

Irma Fredriksson

Karolinska Institutet

Karolinska University Hospital

Per Malmström

Lund University

Skåne University Hospital

Mårten Fernö

Lund University

Lars Malmström

Lund University

Johan Malmstöm

Lund University

Emma Niméus

Skåne University Hospital

Lund University

Communications Biology

23993642 (eISSN)

Vol. 6 1 139

Subject Categories

Medical Genetics

Urology and Nephrology

Cancer and Oncology

DOI

10.1038/s42003-023-04526-6

PubMed

36732562

More information

Latest update

2/15/2023