Cyclo-oxygenase type 2 is dysregulated in breast ductal carcinoma in situ and correlates with poor outcome

Torre, Javier de la; Sabadell, M.D.; Rojo, Federico; Lirola, J.L.; Salicrú, Sabina; Reventós, Jaume; Cajal, Santiago Ramón y; Xercavins, Jordi

doi:10.1016/j.ejogrb.2010.02.033

Cited by 6 publications

(2 citation statements)

References 26 publications

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“…However, in cases with high nuclear staining of phospho-p38, the intensity of COX-2 staining varied from low to high 62. In a few studies, COX-2 was observed to be significantly correlated with high nuclear grade 19, 63, 64. One study showed COX-2 expression to be correlated with cytoplasmic survivin expression in DCIS 54.…”

Section: Resultsmentioning

confidence: 99%

Biological Markers in DCIS and Risk of Breast Recurrence: A Systematic Review

2011

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Understanding of the biology and clinical behavior of ductal carcinoma in situ (DCIS) is currently inadequate. The aim of this comprehensive review was to identify important molecular biological markers associated with DCIS and candidate markers associated with increased risk of ipsilateral recurrence after diagnosis of DCIS. A comprehensive systematic review was performed to identify studies published in the past 10 years that investigated biological markers in DCIS. To be included in this review, studies that investigated the rate of biological expression of markers had to report on at least 30 patients; studies that analyzed the recurrence risk associated with biomarker expression had to report on at least 50 patients. There were 6,252 patients altogether in our review. Biological markers evaluated included steroid receptors, proliferation markers, cell cycle regulation and apoptotic markers, angiogenesis-related proteins, epidermal growth factor receptor family receptors, extracellular matrix-related proteins, and COX-2. Although the studies in this review provide valuable preliminary information regarding the expression and prognostic significance of biomarkers in DCIS, common limitations of published studies (case-series, cohort, and case-control studies) were that they were limited to small patient cohorts in which the extent of surgery and use of radiotherapy or endocrine therapy varied from patient to patient, and variable methods of determining biomarker expression. These constraints made it difficult to interpret the absolute effect of expression of various biomarkers on risk of local recurrence. No prospective validation studies were identified. As the study of biomarkers are in their relative infancy in DCIS compared with invasive breast cancer, key significant prognostic and predictive markers associated with invasive breast cancer have not been adequately studied in DCIS. There is a critical need for prospective analyses of novel and other known breast cancer molecular markers in large cohorts of patient with DCIS to differentiate indolent from aggressive DCIS and better tailor the need and extent of current therapies.

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Section: Resultsmentioning

confidence: 99%

Biological Markers in DCIS and Risk of Breast Recurrence: A Systematic Review

2011

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“…The frequency of COX-2 expression reported in this study (study estimate 55.2%) was similar to that of DCIS or invasive breast cancer in our meta-analyses. One study (de la Torre et al , 2010) met the inclusion criteria in MICB. This study reported COX-2 expression in 74% of samples.…”

Section: Discussionmentioning

confidence: 99%

A systematic review to establish the frequency of cyclooxygenase-2 expression in normal breast epithelium, ductal carcinoma in situ, microinvasive carcinoma of the breast and invasive breast cancer

et al. 2011

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Background:Epidemiological studies have suggested a protective effect of cyclooxygenase (COX)-inhibiting non-steroidal anti-inflammatory drugs in breast cancer risk and disease progression. We performed a systematic review to evaluate the frequency of COX-2 expression in normal breast epithelium, ductal carcinoma in situ of breast (DCIS), DCIS-adjoining invasive breast cancer, microinvasive carcinoma of the breast (MICB) and invasive breast cancer.Methods:Literature searches were carried out on MEDLINE, EMBASE and Web of Science from their commencement until September 2010. Primary studies examining COX-2 expression by immunohistochemistry methodology were included. Meta-analyses were carried out using random effects models for individual study estimates of COX-2 expression and pooled to give an overall estimate.Results:The pooled prevalences (95% confidence intervals) of COX-2 expressions were 53% (44–61) in DCIS studies and 42% (36–49) in the invasive breast cancer studies. There were too few studies involving normal breast epithelium, DCIS-adjoining invasive breast cancer and MICB to conduct meta-analyses.Conclusion:The findings from our meta-analyses have shown similar COX-2 expression in DCIS and invasive breast cancer. This may suggest the involvement of COX-2 in early carcinogenesis. Further studies of COX-2 expression in DCIS are required to investigate the use of COX-2 as a potential drug target for prevention of disease progression in DCIS.

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New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

Hugo

Saunders

Ramsay

et al. 2015

J Mammary Gland Biol Neoplasia

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The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

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Cyclo-oxygenase type 2 is dysregulated in breast ductal carcinoma in situ and correlates with poor outcome

Cited by 6 publications

References 26 publications

Biological Markers in DCIS and Risk of Breast Recurrence: A Systematic Review

Biological Markers in DCIS and Risk of Breast Recurrence: A Systematic Review

A systematic review to establish the frequency of cyclooxygenase-2 expression in normal breast epithelium, ductal carcinoma in situ, microinvasive carcinoma of the breast and invasive breast cancer

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

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