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Clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancers defined by genomic analysis

Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive breast cancer and despite treatment a small fraction (5-10%) of DCIS patients present with invasive disease many years later. A fundamental biologic question is whether the invasive disease recurring in the same breast is established by tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial pure DCIS lesion and paired invasive recurrent tumors in 95 patients together with single cell DNA sequencing in a subset of cases. Our data shows that in 75% the invasive recurrence was clonally related to the initial DCIS, suggesting that the tumor cells were not eliminated during the initial treatment with surgery +/- radiotherapy. Surprisingly however, 18% were clonally unrelated to the DCIS, representing new independent lineages, and 7% of cases were ambiguous. Our findings show that although DCIS is often the precursor of invasive recurrence, a significant fraction of invasive recurrences are unrelated to the initial DCIS. This knowledge is essential for accurate risk evaluation of DCIS treatment de-escalation strategies and the identification of predictive biomarkers.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001008338 Ion Torrent PGM 76
EGAD00001008376 Illumina HiSeq 2500 105
EGAD00001008379 unspecified 96
EGAD00001008380 Illumina HiSeq 2500 33
EGAD00001008401 Illumina HiSeq 2500 Ion Torrent PGM 52
Publications Citations
Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer.
Nat Genet 54: 2022 850-860