A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer

Paik, Soonmyung; Shak, Steven; Tang, Gong; Kim, Chungyeul; Baker, Joffre B.; Cronin, Maureen; Baehner, Frederick L.; Walker, Michael G.; Watson, Drew; Park, Taesung; Hiller, W. D. B.; Fisher, Edwin R.; Wickerham, D. Lawrence; Bryant, John; Wolmark, Norman

doi:10.1056/nejmoa041588

Cited by 5,521 publications

(4,980 citation statements)

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“…The survival of ER + patients with high ferroportin and low hepcidin gene expression seen in Fig. 6B is comparable to that of ER + , node-negative patients classified into the good outcome group by the Oncotype Dx 21-gene panel (48). Using combined ferroportin and hepcidin gene expression, we identified not only node-negative but also node-positive, ER + breast cancer patients who exhibit this good outcome (41% of the high ferroportin and low hepcidin expressors in our study were node-positive at diagnosis).…”

Section: Discussionmentioning

confidence: 62%

Ferroportin and Iron Regulation in Breast Cancer Progression and Prognosis

Pinnix¹,

Miller²,

Wang³

et al. 2010

Science Translational Medicine

246

278

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Ferroportin and hepcidin are critical proteins for the regulation of systemic iron homeostasis. Ferroportin is the only known mechanism for export of intracellular non–heme-associated iron; its stability is regulated by the hormone hepcidin. Although ferroportin profoundly affects concentrations of intracellular iron in tissues important for systemic iron absorption and trafficking, ferroportin concentrations in breast cancer and their influence on growth and prognosis have not been examined. We demonstrate here that both ferroportin and hepcidin are expressed in cultured human breast epithelial cells and that hepcidin regulates ferroportin in these cells. Further, ferroportin protein is substantially reduced in breast cancer cells compared to nonmalignant breast epithelial cells; ferroportin protein abundance correlates with metabolically available iron. Ferroportin protein is also present in normal human mammary tissue and markedly decreased in breast cancer tissue, with the highest degree of anaplasia associated with lowest ferroportin expression. Transfection of breast cancer cells with ferroportin significantly reduces their growth after orthotopic implantation in the mouse mammary fat pad. Gene expression profiles in breast cancers from >800 women reveal that decreased ferroportin gene expression is associated with a significant reduction in metastasis-free and disease-specific survival that is independent of other breast cancer risk factors. High ferroportin and low hepcidin gene expression identifies an extremely favorable cohort of breast cancer patients who have a 10-year survival of >90%. Ferroportin is a pivotal protein in breast biology and a strong and independent predictor of prognosis in breast cancer.

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Section: Discussionmentioning

confidence: 62%

Ferroportin and Iron Regulation in Breast Cancer Progression and Prognosis

Pinnix¹,

Miller²,

Wang³

et al. 2010

Science Translational Medicine

246

278

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“…Luminal B was previously shown to have a more aggressive phenotype, higher HG, and more proliferative index such as Ki67 than luminal A 30, 31, 32. The prognosis of patients with luminal B tumors was also found to be worse than those with luminal A tumors despite treatments with hormonal therapy 33. These discrepancies between luminal A and B may be due to different estrogen‐related intracellular signaling pathways in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of the ubiquitin ligase carboxyl terminus of the Hsc70‐interacting protein in postmenopausal breast cancer

et al. 2016

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The carboxyl terminus of the Hsc70‐interacting protein (CHIP) is considered to induce the ubiquitination and degradation of several oncogenic proteins, and play a role in the inhibition of tumor progression and invasion under experimental conditions. However, the impact of CHIP expression on the prognosis of breast cancer patients has not yet been established. In this study, using an immunohistochemical method, 272 patients with invasive breast cancer were assessed for the expression of CHIP (graded scores 0‐3) and the statuses of biomarkers, such as estrogen receptor (ER), progesterone receptor (PgR), and HER2. The relationships between the statuses of CHIP and biomarkers as well as clinical features were also evaluated, and that between the expression of CHIP and patient prognosis was analyzed. We revealed that the strong expression of CHIP correlated with positive ER (P < 0.001), positive PgR (P < 0.001), and negative HER2 (P = 0.02). In postmenopausal patients, relapse‐free survival (RFS) was significantly better in the high CHIP group than in the low CHIP group (P = 0.042). In addition, RFS and cancer‐specific survival (CSS) were significantly better in patients with ER‐positive/CHIP score 3 tumors than in those with ER‐negative/CHIP score 0 tumors (RFS: P = 0.038, CSS: P = 0.0098). The methylation status of CHIP gene promoter did not always account for the down‐regulation of its expression. In conclusion, the overexpression of CHIP is a potent prognostic factor of a good prognosis in ER‐positive breast cancer patients in the postmenopausal phase.

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“…Specifically we looked at relative methylation values prior to administration of AZA and the ratio of gene expression following administration of AZA to before. The methylation values were obtained from a Nimblegen promoter array using the Methyl-DNA immunoprecipitation (MeDIP) technique [40,41]. Gene expression ratios were obtained using a custom 2-channel Nimblegen array.…”

Section: Methodsmentioning

confidence: 99%

A semantic web framework to integrate cancer omics data with biological knowledge

et al. 2012

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BackgroundThe RDF triple provides a simple linguistic means of describing limitless types of information. Triples can be flexibly combined into a unified data source we call a semantic model. Semantic models open new possibilities for the integration of variegated biological data. We use Semantic Web technology to explicate high throughput clinical data in the context of fundamental biological knowledge. We have extended Corvus, a data warehouse which provides a uniform interface to various forms of Omics data, by providing a SPARQL endpoint. With the querying and reasoning tools made possible by the Semantic Web, we were able to explore quantitative semantic models retrieved from Corvus in the light of systematic biological knowledge.ResultsFor this paper, we merged semantic models containing genomic, transcriptomic and epigenomic data from melanoma samples with two semantic models of functional data - one containing Gene Ontology (GO) data, the other, regulatory networks constructed from transcription factor binding information. These two semantic models were created in an ad hoc manner but support a common interface for integration with the quantitative semantic models. Such combined semantic models allow us to pose significant translational medicine questions. Here, we study the interplay between a cell's molecular state and its response to anti-cancer therapy by exploring the resistance of cancer cells to Decitabine, a demethylating agent.ConclusionsWe were able to generate a testable hypothesis to explain how Decitabine fights cancer - namely, that it targets apoptosis-related gene promoters predominantly in Decitabine-sensitive cell lines, thus conveying its cytotoxic effect by activating the apoptosis pathway. Our research provides a framework whereby similar hypotheses can be developed easily.

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A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer

Abstract: The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer.

Cited by 5,521 publications

References 37 publications

Ferroportin and Iron Regulation in Breast Cancer Progression and Prognosis

Ferroportin and Iron Regulation in Breast Cancer Progression and Prognosis

Prognostic value of the ubiquitin ligase carboxyl terminus of the Hsc70‐interacting protein in postmenopausal breast cancer

A semantic web framework to integrate cancer omics data with biological knowledge

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