Open this publication in new window or tab >>Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden..
Lund Univ, Skane Univ Hosp, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
Univ Gothenburg, Inst Clin Sci, Dept Surg, Sahlgrenska Acad, Gothenburg, Sweden..
Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Breast Endocrine Tumors & Sarcoma, Stockholm, Sweden..
Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden.;Skane Univ Hosp, Dept Haematol Oncol & Radiat Phys, Lund, Sweden..
Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden..
Lund Univ, Fac Med, Dept Clin Sci Lund, Div Infect Med, Lund, Sweden..
Lund Univ, Fac Med, Dept Clin Sci Lund, Div Infect Med, Lund, Sweden..
Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden.;Skane Univ Hosp, Dept Surg, Lund, Sweden..
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2023 (English)In: Communications Biology, E-ISSN 2399-3642, Vol. 6, no 1, article id 139Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-498451 (URN)10.1038/s42003-023-04526-6 (DOI)000925802900001 ()36732562 (PubMedID)
Funder
Lund University
2023-03-162023-03-162023-03-16Bibliographically approved