Abrogated Response to Cellular Stress Identifies DCIS Associated with Subsequent Tumor Events and Defines Basal-like Breast Tumors
Open accessAbstract
Approximately 15%-30% of women diagnosed with ductal carcinoma in situ (DCIS) develop a subsequent tumor event within 10 years after surgical lumpectomy. To date, little is known about the molecular pathways that confer this differential risk for developing subsequent disease. In this study, we demonstrate that expression of biomarkers indicative of an abrogated response to cellular stress predicts DCIS with worse outcome and is a defining characteristic of basal-like invasive tumors. Mechanistic studies identify the Rb pathway as a key regulator of this response. Conversely, biomarkers indicative of an intact response to cellular stress are strongly associated with a disease-free prognosis. Assessment of these biomarkers in DCIS begins to allow prediction of tumor formation years before it actually occurs.
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Loss of RB function is associated with a greater chance of recurring invasive basal-like breast cancer.
“A recent report indicates that loss of RB function is associated with increased levels of cyclooxygenase 2 (COX2) and an increased chance of recurring invasive basal-like breast cancer138.”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [138]
Loss of RB function is associated with higher COX2 levels.
“A recent report indicates that loss of RB function is associated with increased levels of cyclooxygenase 2 (COX2) and an increased chance of recurring invasive basal-like breast cancer138.”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [138]
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- Authors
- Gauthier, M. L., Berman, H. K., Miller, C., Kozakeiwicz, K., Chew, K., Moore, D., Rabban, J., Chen, Y. Y., Kerlikowske, K., & Tlsty, T. D.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Tlsty, Thea D.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 12
- Issue
- 5
- Pages
- 479-491
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3605202
- OpenAlex
- W2055395862
- Cited by
- 214
- References
- 4
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 13 · 2018: 8 · 2017: 8 · 2016: 10 · 2015: 8 · 2014: 8 · 2013: 22 · 2012: 21
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute (R01CA097214, P50CA058207, P50-CA 58207)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- ductal carcinoma in situ, basal-like breast cancer, cellular stress response, Rb pathway, disease-free survival, prognostic factors, breast-conserving surgery, cancer recurrence risk
- MeSH terms
- Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Cell Cycle, Female, Humans, Models, Biological, Prognosis, Risk, RNA, Messenger, Biomarkers, Tumor, Retinoblastoma Protein, Treatment Outcome, Cyclin-Dependent Kinase Inhibitor p16, Cell Proliferation, Cyclooxygenase 2
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