Pusem PATIR, Burçak KARACA, Alper ŞENER, Osman ZEKİOĞLU, Güray SAYDAM, Canfeza SEZGİN

Molecular Subtype Distribution and Cyclooxygenase-2 Expression Situation in Inflammatory Breast Cancer

Amaç: Enflamatuvar meme kanseri (EMK), lokal ilerlemiş meme kanserinin agresif bir alt tipidir. Günümüzde EMK'lı kadınların hemen hepsi lenf nodu tutulumuna ve yaklaşık üçte biri de uzak metastaza sahiptir. Bu yüzden EMK'nın moleküler biyolojisinin anlaşılmasına ve yeni tedavi seçeneklerine ihtiyaç vardır. Bu çalışmanın amacı EMK'nın agresif ve fatal seyrinde moleküler doğasının rol oynayabileceğini ve siklooksijenaz-2 inhibitörlerinin EMK tedavisinde hedefe yönelik tedavi seçeneği olabileceğini göstermektir. Gereç ve Yöntemler: Ege Üniversitesi Tıp Fakültesi Medikal Onkoloji Anabilim Dalı'nda 2000-2009 yıllarında meme kanseri tedavisi gören hastalardan sağlanan EMK örnekleri retrospektif olarak değerlendirildi. İmmünohistokimyasal analiz özel meme kanseri patoloğu tarafından yapıldı ve immünohistokimyasal puanlama boyanma yoğunluğu ve yüzdesi kullanılarak belirlendi. Bulgular: EMK hastalarının %31'i bazal tip, %22'si luminal B/insan epidermal büyüme faktörü reseptörü 2 (HER2)- tip, %22'si luminal B/HER2+ tip, %17'si HER2 tip, %8'i luminal A tip olarak tanımlanmıştır. Hastaların %92,6'sında siklooksijenaz-2 ekspresyonu pozitif bulunmuştur. Sonuç: Bu bağlamda, EMK'nın kötü prognoza ve sağkalıma sahip olmasının nedenlerinden birinin EMK'nın moleküler doğası olabileceği ve ayrıca EMK'da siklooksijenaz-2 yolağının önemli bir hedefe yönelik tedavi seçeneği olabileceği görülmüştür.

Enflamatuvar Meme Kanserinde Moleküler Alt Tip Dağılımı ve Siklooksijenaz-2 Ekspresyon Durumu

Objective: Inflammatory breast cancer (IBC) is a rare and aggressive form of locally advanced breast cancer. Currently, almost all women with IBC have lymph node involvement and approximately one-third have distant metastases. Therefore, there is still need for understanding of the molecular biology and new therapy alternatives in IBC. The purpose of this study was to determine the potential role of the cyclooxygenase-2 (COX-2) expression pattern in the aggressive and fatal course of IBC and to investigate the possibility of using COX-2 inhibitors as therapy options in the treatment of IBC. Materials and Methods: IBC samples obtained from breast cancer patients treated Between 2000-2009 in Ege University Faculty of Medicine Department of Medical Oncology were retrospectively evaluated. Immunohistochemical analysis was performed by a special breast cancer pathologist and manually assessed using an immunohistochemical scoring for both staining intensity and percentage. Results: In this study, the molecular subtypes identified in IBC patients were: basal (31%), luminal B/human epidermal growth factor receptor 2 (HER2)- (22%), luminal B/HER2+ (22%), HER2 (17%) and luminal A (8%). COX-2 expression was found to be positive in 92.6% of patients. Conclusion: In this context, it was concluded that the relatively high expression rate of COX-2 could be a reason for poor prognosis and also might lead to the use of COX-2 inhibitors not only as a single agent but also in combination with current chemotherapeutic agents in patients with IBC.

PDF

___

Lee BJ, Tannenbaum EN. Inflammatory carcinoma of the breast. Surg Gynecol Obstet 1924; 39: 580-95.
Hance KW, Anderson WF, Devesa SS, Young HA, Levine PH. Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst 2005; 97: 966-75.
Anderson WF, Schairer C, Chen BE, Hance KW, Levine PH. Epidemiology of inflammatory breast cancer (IBC). Breast Dis 2006; 22: 9-23.
Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington J, et al. Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. J Natl Cancer Inst 2010; 102: 627-37.
Van Laere SJ, Van den Eynden GG, Van der Auwera I, Vandenberghe M, van Dam P, Van Marck EA, et al. Identification of cell-of-origin breast tumor subtypes in inflammatory breast cancer by gene expression profiling. Breast Cancer Res Treat 2006; 95: 243-55.
Kertmen N, Babacan T, Keskin O, Solak M, Sarici F, Akin S, et al. Molecular subtypes in patients with inflammatory breast cancer; a single center experience. J BUON 2015; 20: 35-9.
Denkert C, Winzer KJ, Müller BM, Weichert W, Pest S, Köbel M, et al. Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease-free survival and overall survival in patients with breast carcinoma. Cancer 2003; 97: 2978-87.
Half E, Tang XM, Gwyn K, Sahin A, Wathen K, Sinicrope FA. Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ. Cancer Res 2002; 62: 1676-81.
Glover JA, Hughes CM, Cantwell MM, Murray LJ. 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. Br J Cancer 2011; 105: 13-7.
Friedman GD, Ury HK. Initial screening for carcinogenicity of commonly used drugs. J Natl Cancer Inst 1980; 65: 723-33.
Ashok V, Dash C, Rohan TE, Sprafka JM, Terry PD. Selective cyclooxygenase-2 (COX-2) inhibitors and breast cancer risk. Breast 2011; 20: 66-70.
Subbaramaiah K, Hart JC, Norton L, Dannenberg AJ. Microtubule-interfering agents stimulate the transcription of cyclooxygenase-2. Evidence for involvement of ERK1/2 AND p38 mitogen-activated protein kinase pathways. J Biol Chem 2000; 275: 14838-45.
Falandry C, Canney PA, Freyer G, Dirix LY. Role of combination therapy with aromatase and cyclooxygenase-2 inhibitors in patients with metastatic breast cancer. Ann Oncol 2009; 20: 615- 20.
Arun B, Goss P. The role of COX-2 inhibition in breast cancer treatment and prevention. Semin Oncol 2004; 31(2 Suppl 7): 22- 9.