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 139Subject Categories (SSIF 2011)
Medical Genetics
Urology and Nephrology
Cancer and Oncology
DOI
10.1038/s42003-023-04526-6
PubMed
36732562