Mehmet YILDIRIM, Nazif ERKAN, Hakan POSTACI, Durmuş Ali ÇETİN, Elif SELEK, Levent GENÇ, Volkan TEKİN

MEME KANSERLERİ SUBGRUPLARININ SIKLIĞI VE SAĞKALIM ÜZERİNE ETKİLERİ

Meme kanseri kadınlarda en sık görülen kanser türüdür ve 40-44 yaş arası kadınlarda kanser ölümlerinin başlıca nedenidir. Son dönemlerde meme kanserinin tanısında, evrelendirilmesinde ve tedavisinde kaydedilen ilerlemeler, hastaların sağkalımlarında önemli ölçüde düzelme sağlamıştır. Uzun yıllardır histoloji ve morfolojinin ön planda tutulduğu bir klasifikasyon kullanılmaktadır. Fakat günümüzde, aynı tedaviye rağmen aynı histoloji ve klinik evredeki hastaların, yaşam seyirlerinin farklı olabildiği görülmüştür. Moleküler tanımlamalardaki farklılıkların prognoz üzerine etkili olduğu görülmüştür. Çalışmamızın amacı kliniğimizde tanı ve tedavi almış meme kanseri olgularının, değerlendirilmesidir. Çalışmaya kliniğimizde Ocak 2005 ile Ocak 2010 tarihleri arasında meme kanseri nedeniyle ameliyat edilen 74 hasta alınmıştır. Patoloji raporlarına göre hastalar, hormon reseptör ve c-erbB2 durumuna göre, Luminal A hormon reseptör pozitif ve Her–2 negatif , Luminal B hormon reseptör pozitif ve Her–2 pozitif , Triple negatif hormon Reseptör negatif ve Her–2 negatif ve Her-2 overekspresyonu hormon reseptör negatif ve Her– 2 pozitif olmak üzere 4 subgruba ayrıldı. Çalışmamızda olgular, yaş, tümör boyutu, lenf nodunun metastaz durumu, histolojik grade, histolojik tip, p53 mutasyonu, Ki-67 durumu, ameliyat türü, hastalıksız sağkalım ve genel sağkalım süreleri açısından değerlendirildi. İmmünohistokimyasal özellikleri itibariyle, 21 %28,4 hasta luminal A subgrubuna, 24 %32,4 hasta luminal B subgrubuna, 12 %16,2 hasta Her-2 overekspresyon subgrubuna, 17 %23 hasta Triple negatif subgruba dahil edildi. Hastaların, hastalıksız sağkalım sürelerinin ortalamaları sırasıyla, Luminal A subgrubunda 47,86 ay, Luminal B subgrubunda 45,17 ay, Triple negatif subgrupta 53,18 ay, Her 2 overekspresyonu subgrubunda 48,17 ay olarak saptandı. Hastalar sağkalımları açısından incelendiğinde; Luminal A subgrubunda 1 %4,8 hastada, Luminal B subgrubunda 3 %12,5 hastada, Triple negatif subgrupta 2 %11,8 hastada, Her 2 overekspresyonu subgrubunda 1 %8,3 hastada mortalite saptandı. Luminal A hasta subgrubunda; aksilla lenf nodu evresi, tümörün histolojik tipi, tümörün büyüklüğü sağkalım üzerine etkili bulunmuşken, Her-2 overekspresyonu hasta subgrubunda; yaş, aksilla lenf nodu evresi, tümörün büyüklüğü sağkalım üzerine etkili bulunmuştur. Meme kanserlerinin subgruplarına ayrılmasındaki amaç hormonoterapi ve monoklonal antikor bazında tedaviler yapılacak grupların seçimidir. Meme kanserlerininaçısından sınıflandırılması, uzun yıllardır kullanılan histoloji ve morfolojinin ön planda tutulduğu sınıflandırmaya alternatif olabilir. moleküler olarak gen ekspresyon profilleri

Anahtar Kelimeler:

Meme kanseri moleküler sınıflama, Luminal A, Luminal B, Triple Negatif, Her-2 overekspresyonu

FREQUENCY OF BREAST CANCER’S SUBGROUPS AND EFFECT FOR SURVIVAL

Breast cancer is the most common cancer type in women and major cause of cancer death in women between the ages of 40-44. Recently, advences in the diagnosis, staging and treatment of breast cancer, provided considerably improvement of patients survival. For many years, a classification has been used that kept in the forefront of histology and morphology. But nowadays, despite the same treatment of patients with the same histology and clinical stage, prognosis can be seen in different. The definitions of molecular differences has positive effects on prognosis. The purpose of this study, identify subgroup, and evaluate the effects on survival of the had diagnosis and treatment of breast cancer cases in our clinic. From January 2005 to January 2010, 74 patients who operated for breast cancer in our clinic were enroled in this study. Patients were divided into four subgroup according to hormone receptor and c-erbB2 status. These subgroups were; Luminal A hormone receptor positive and Her–2 negative , Luminal B hormone receptor positive and Her–2 positive , triple negative hormone receptor negative and Her–2 negative and Her-2 overexpressing hormone receptor negative ve Her–2 positive . In our study, patients age, tumor size, lymph node metastatic status, histological grade, histological type, p53 mutation, Ki-67 status, surgery type, disease free survival and overall survival times were analyzed. According to immunohistochemical characteristics, 21 28,4% patients were included in Luminal A subgroup, 24 32,4% patients were included Luminal B subgroup, 17 23% patients were included in triple negative subgroup, 12 16,2% patients were included Her-2 overexpressing subgroup. The mean disease free survival times of patients were 47,86 months for Luminal A, 45,17 months for Luminal B, 53,18 months for Triple negative, 48,17 months for Her-2 overexpressing. Patients were analyzed by means of survival, the mortality rate 4,8% for Luminal A, 12,5% for Luminal B, 11,8% for Triple negative, 8,3% for Her-2 overexpressing. Axillary lymph node stage, tumor histological type and tumor size were found to affect on survival in Luminal A subgroup. Age, axillary lymph node stage and tumor size were found to affect on survival in Her-2 overexpressing subgroup. The aim of seperation breast cancer to subgrups; determine the groups which to be treated with hormonal treatments or monoclonal antibody. In terms of gene expression profiles as a molecular classification of breast cancers are may be alternative for the classification used in the histology and morphology

Keywords:

Molecular classification of breast cancer, Luminal A, Luminal B, Triple Negative, Her-2 overexpressing,

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) The Centers for Disease Control and Prevention (US). Deaths from Breast Cancer United States 1991. JAMA 1994; 125:1395-7.
) Hoover R. Breast Cancer: Geographic, Migrant, and Time-Trend Patterns. In: Fortner JSP, ed. Accomplishments in cancer research. New York: Lippincott- Raven, 1996: 403-25.
) Rosen PP. Immunohistochemical detection of HER-2/neu in patients with axillary lymph node negative breast carcinoma cancer. BMJ 1995; 75: 1320- 6.
) Sorlie T, Perou CM, Tibshirani R. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 2001;98:10869–74.
) Sorlie T, Tibshirani R, Parker J. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 2003; 100:8418–23.
) Gusterson A.B,Ross T.D, Heath J.V,Stein T. Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer. Breast cancer reseach 2005,7:143- 8.
) Fulford LG, Easton DF, Reis- Filho JS, et al. Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast. Histopathology 2006; 49: 22-34. 8) Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen
progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: A population-based study from the California Cancer Registry. Cancer 2007; 109:1721-8.
(ER)-negative 9) Cleator S, Heller W, Coombes RC. Triple-negative breast cancer
therapeutic options. Lancet Oncol 2007; 8:235-44.
) . Dawson SJ, Provenzano E, Caldas C. Triple-negative breast cancers: clinical and prognostic implications. Eur J Cancer 2009; 45(suppl 1):27-40.
) Linderholm B, Lindh B, Tavelin B et al.
growthfactor (VEGF) expression predicts outcome in 833 patients with primary breast carcinoma. Int J Cancer 2000; 89: 62.
vascular-endothelial- 12) Linderholm BK, Lindahl T, Holmberg L et al. The expression of vascular endothelial growth factor correlates with mutant p53 and poor prognosis in human breast cancer. Cancer Res 2001; 61: 2256–60.
) Kwan ML, Kushi LH, Weltzien E et al (2009) Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res 11:R31
) Lund MJ, Trivers KF, Porter PL, et al. Race and triple negative threats to breast
populationbased study in Atlanta, GA. Breast Cancer Res Treat 2009; 113:357- 70. survival
a 15) Bouchalova K, Cizkova M, Cwiertka K, et al. Triple negative breast cancer: current status and prospective targeted treatment based on HER1 (EGFR), TOP2A, and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2009; 153:13-7.
) Luck AA, Evans AJ, Green AR, et al. The influence of basal phenotype on the metastatic pattern of breast cancer. Clin Oncol (R Coll Radiol) 2008; 20:40–5.
) Ünal A. Meme Kanserleri. Klinik Cerrahi
Klinikleri Yayınevi, 1997, Ankara. 1.Baskı
Türkiye 18) Dees EC, Shulman LN, Souba WW, Smith BL. Does information from axillary dissection change treatment in clinically node-negative patients with breast cancer? An algorithm for assessment of impact of axillary dissection. Ann Surg 19;226:279- 86.
) Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, Harris L, Hait W, Toppmeyer D: Locoregional
metastasis in conservatively managed triple negative earlystage breast cancer. J Clin Oncol 2006; 24:5652-7.
distant 20) Ihemelandu CU, Naab TJ, Mezghebe HM, Makambi KH, Siram SM, Leffall LD Jr, Dewitty RL Jr, Frederick WA. Basal cell-like (triple-negative) breast cancer, a predictor of distant metastasis in African American women. Am J Surg 2008 ;195:153-8.
) Hicks DG, Sm Short, Prescott NL et al. Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin 5/6, and overexpress HER2 or EGFR. Am J Surg Pathol 2006; 30:1097–1104.
) Ridriguez-Pinilla SM, Sarrio D, Honrado E et al (2006) Prognostic significance of basal-like phenotype and fascin expression in node-negative invasive breast cancers. Clin Cancer Res 2006; 12:1533–9.
) Dent R, Hanna WM, Trudeau M, et al. Pattern of metastatic spread in triple- negative breast cancer. Breast Cancer Res Treat 2009; 115:423–8.
) Linderholm BK, Hellborg H, Johansson U, Elmberger G, Skoog L, Lehtiö J, Lewensohn R. Significantly higher levels of vascular endothelial growth factor (VEGF) and shorter survival times for patients with primary operable triple-negative breast cancer. Ann Oncol 2009;20:1639-46.
) Billar JA, Dueck AC, Stucky CC, Gray RJ, Wasif N, Northfelt DW, McCullough AE, Pockaj BA. Triple-negative breast cancers: unique clinical presentations and outcomes. Ann Surg Oncol 2010; 17:384-90.
Yazının alınma tarihi:08.04.2013
Kabül tarihi:30.04.2013
Online basım:02.05.2013
İzmir Eğitim ve Araştırma Hastanesi Tıp Dergisi,2013;17:88-97