PMID- 31420779
OWN - NLM
STAT- MEDLINE
DCOM- 20200226
LR  - 20240416
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 178
IP  - 2
DP  - 2019 Nov
TI  - Genomic landscape of ductal carcinoma in situ and association with progression.
PG  - 307-316
LID - 10.1007/s10549-019-05401-x [doi]
AB  - PURPOSE: The detection rate of breast ductal carcinoma in situ (DCIS) has 
      increased significantly, raising the concern that DCIS is overdiagnosed and 
      overtreated. Therefore, there is an unmet clinical need to better predict the 
      risk of progression among DCIS patients. Our hypothesis is that by combining 
      molecular signatures with clinicopathologic features, we can elucidate the 
      biology of breast cancer progression, and risk-stratify patients with DCIS. 
      METHODS: Targeted exon sequencing with a custom panel of 223 genes/regions was 
      performed for 125 DCIS cases. Among them, 60 were from cases having concurrent or 
      subsequent invasive breast cancer (IBC) (DCIS + IBC group), and 65 from cases 
      with no IBC development over a median follow-up of 13 years (DCIS-only group). 
      Copy number alterations in chromosome 1q32, 8q24, and 11q13 were analyzed using 
      fluorescence in situ hybridization (FISH). Multivariable logistic regression 
      models were fit to the outcome of DCIS progression to IBC as functions of 
      demographic and clinical features. RESULTS: We observed recurrent variants of 
      known IBC-related mutations, and the most commonly mutated genes in DCIS were 
      PIK3CA (34.4%) and TP53 (18.4%). There was an inverse association between PIK3CA 
      kinase domain mutations and progression (Odds Ratio [OR] 10.2, p < 0.05). Copy 
      number variations in 1q32 and 8q24 were associated with progression (OR 9.3 and 
      46, respectively; both p < 0.05). CONCLUSIONS: PIK3CA kinase domain mutations and 
      the absence of copy number gains in DCIS are protective against progression to 
      IBC. These results may guide efforts to distinguish low-risk from high-risk DCIS.
FAU - Lin, Chieh-Yu
AU  - Lin CY
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA, 
      USA.
AD  - Department of Pathology and Immunology, School of Medicine, Washington University 
      in St. Louis, St. Louis, MO, USA.
FAU - Vennam, Sujay
AU  - Vennam S
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Purington, Natasha
AU  - Purington N
AD  - Department of Medicine, Quantitative Sciences Unit, Stanford University, 
      Stanford, CA, USA.
FAU - Lin, Eric
AU  - Lin E
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Varma, Sushama
AU  - Varma S
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Han, Summer
AU  - Han S
AD  - Department of Medicine, Quantitative Sciences Unit, Stanford University, 
      Stanford, CA, USA.
FAU - Desa, Manisha
AU  - Desa M
AD  - Department of Medicine and of Biomedical Data Science, Quantitative Sciences 
      Unit, Stanford University, Stanford, CA, USA.
FAU - Seto, Tina
AU  - Seto T
AD  - Research Information Technology, Stanford University School of Medicine, 
      Stanford, CA, USA.
FAU - Wang, Nicholas J
AU  - Wang NJ
AD  - Department of Biomedical Engineering, Oregon Health and Science University, 
      Portland, OR, USA.
FAU - Stehr, Henning
AU  - Stehr H
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Troxell, Megan L
AU  - Troxell ML
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Kurian, Allison W
AU  - Kurian AW
AD  - Departments of Medicine and of Health Research and Policy, Stanford University 
      School of Medicine, Stanford, CA, USA.
FAU - West, Robert B
AU  - West RB
AUID- ORCID: 0000-0002-8330-8283
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA, 
      USA. rbwest@stanford.edu.
LA  - eng
GR  - R01 CA193694/CA/NCI NIH HHS/United States
GR  - U58 DP000807/DP/NCCDPHP CDC HHS/United States
GR  - HHSN261201000035I/CA/NCI NIH HHS/United States
GR  - UL1 RR025744/RR/NCRR NIH HHS/United States
GR  - P30 CA124435/CA/NCI NIH HHS/United States
GR  - UL1 TR003142/TR/NCATS NIH HHS/United States
GR  - HHSN261201000140C/CA/NCI NIH HHS/United States
GR  - R01CA193694/NH/NIH HHS/United States
GR  - HHSN261201000035C/PC/NCI NIH HHS/United States
GR  - HHSN261201000034C/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20190817
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Ductal, Breast/*genetics/*pathology/therapy
MH  - Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology
MH  - DNA Copy Number Variations
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - *Genome-Wide Association Study/methods
MH  - *Genomics/methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Tumor Burden
PMC - PMC6800639
MID - NIHMS1537661
OTO - NOTNLM
OT  - Breast cancer
OT  - Copy number variant
OT  - Ductal carcinoma in situ
OT  - PIK3CA
COIS- Conflict of Interest The authors declare that they have no competing interests.
EDAT- 2019/08/20 06:00
MHDA- 2020/02/27 06:00
PMCR- 2020/11/01
CRDT- 2019/08/18 06:00
PHST- 2019/05/03 00:00 [received]
PHST- 2019/08/07 00:00 [accepted]
PHST- 2019/08/20 06:00 [pubmed]
PHST- 2020/02/27 06:00 [medline]
PHST- 2019/08/18 06:00 [entrez]
PHST- 2020/11/01 00:00 [pmc-release]
AID - 10.1007/s10549-019-05401-x [pii]
AID - 10.1007/s10549-019-05401-x [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2019 Nov;178(2):307-316. doi: 
      10.1007/s10549-019-05401-x. Epub 2019 Aug 17.