The impact of isolated local recurrence on long-term outcome in early-breast cancer patients after breast-conserving therapy

Vrieling, Conny; Assele, Samson; Moser, Lotte; Sauvé, Nicolas; Litière, Saskia; Poortmans, Philip; Struikmans, H.; Tienhoven, Geertjan van; Bartelink, Harry; Collette, Laurence

doi:10.1016/j.ejca.2021.06.018

Cited by 4 publications

(2 citation statements)

References 23 publications

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“…IBTR is a clinically important event in BC, an isolated in-breast recurrence is a potentially curable event but associated with an increased risk of distant metastases (DM) and breast cancer death [4][5][6][7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

”Evolution of ipsilateral breast cancer decoded by proteogenomics”

Marchi

Pyl²,

Sjöström

et al. 2022

Preprint

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Ipsilateral breast tumor recurrence (IBTR) is a clinically important event, where an isolated in-breast recurrence is a potentially curable event but also associated with an increased risk of distant metastases and breast cancer death. It currently remains unclear if IBTRs are associated with molecular changes that can be explored as a resource for precision medicine strategies targeting locally recurring breast cancer. Here, we employed a recently developed proteogenomics workflow to analyze a cohort of 27 primary breast cancers and their matched IBTRs by whole genome sequencing, RNA sequencing, and mass spectrometry-based proteomics to define proteogenomic features of tumor evolution. Analysis of mutational signatures, copy number changes, and cancer specific mutations revealed a relationship with estrogen and progesterone receptor statuses and increased levels of genetic change. This in turn altered the re-programming of the transcriptome and proteome towards a recurring molecular disease phenotype with high replicating capacity and a higher degree of genomic instability possibly enhanced by high expression of APOBEC3B. In conclusion, this study defines how primary breast tumors differentially evolve into different ipsilateral recurrent malignancies depending on their key biomarker status, suggesting that further enhancing the genomic instability in some tumors could serve as an alternative treatment option.

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Section: Introductionmentioning

confidence: 99%

”Evolution of ipsilateral breast cancer decoded by proteogenomics”

Marchi

Pyl²,

Sjöström

et al. 2022

Preprint

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“…Still, about 4-11% of BCs develop a ipsilateral breast tumor recurrence (IBTR) within 10 years 2,3 . IBTR is a clinically important event in BC, where an isolated in-breast recurrence is a potentially curable event but associated with an increased risk of distant metastases and breast cancer death [4][5][6][7][8][9] . The time interval between IBTR and distant metastases constitutes a therapeutic window to prevent further spread.…”

mentioning

confidence: 99%

Proteogenomics decodes the evolution of human ipsilateral breast cancer

et al. 2023

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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.

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