Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer.

Journal Article (Journal Article)

Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers.

Full Text

Duke Authors

Cited Authors

  • Lips, EH; Kumar, T; Megalios, A; Visser, LL; Sheinman, M; Fortunato, A; Shah, V; Hoogstraat, M; Sei, E; Mallo, D; Roman-Escorza, M; Ahmed, AA; Xu, M; van den Belt-Dusebout, AW; Brugman, W; Casasent, AK; Clements, K; Davies, HR; Fu, L; Grigoriadis, A; Hardman, TM; King, LM; Krete, M; Kristel, P; de Maaker, M; Maley, CC; Marks, JR; Menegaz, BA; Mulder, L; Nieboer, F; Nowinski, S; Pinder, S; Quist, J; Salinas-Souza, C; Schaapveld, M; Schmidt, MK; Shaaban, AM; Shami, R; Sridharan, M; Zhang, J; Stobart, H; Collyar, D; Nik-Zainal, S; Wessels, LFA; Hwang, ES; Navin, NE; Futreal, PA; Grand Challenge PRECISION consortium, ; Thompson, AM; Wesseling, J; Sawyer, EJ

Published Date

  • June 2022

Published In

Volume / Issue

  • 54 / 6

Start / End Page

  • 850 - 860

PubMed ID

  • 35681052

Pubmed Central ID

  • PMC9197769

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/s41588-022-01082-3


  • eng

Conference Location

  • United States