Aldehyde dehydrogenase-1 expression and prognosis in triple-negative breast cancer

Received: 15 Aug. 2014, Revised 20 Aug. 2014, Accepted 24 Aug. 2014, Available Online 30 Aug. 2014 İstanbul University, Faculty of Medicine, Department of Internal Medicine, Istanbul, Turkey 2 İstanbul University, Faculty of Medicine, Department of Medical Oncology, Istanbul, Turkey Celal Bayar University, Faculty of Medicine, Department of Radiation Oncology, Manisa Turkey Istanbul University, Faculty of Medicine, Department of Pathology, İstanbul, Turkey *Corresponding Author: Edvin Murrja E-mail: dredvin@yahoo.com Aldehyde dehydrogenase-1 expression and prognosis in triple-negative breast cancer Edvin Murrja 1 , Zeynep Hande Turna 2 , Mehmet Akif Ozturk 2 , Ahmet Cinkaya 3 , Tulin Ozturk 4


Introduction
Triple-negative breast cancer is defined by absent expression of the estrogen receptor [ER], progesterone receptor [PR], and the human epidermal growth factor receptor 2 [HER2] negative status [1].Given the lack of these biologic markers endocrine therapy and HER2-directed therapies are not recommended in the treatment of TNBC [18][19][20].Although the same general principles used in the diagnosis and treatment of non-triple-negative breast cancer generally apply to TNBC, it has a lot of differences in risk factors, molecular and histologic features, clinical behavior and chemotherapy sensitivity [2][3][4][5][6].TNBC defines a heterogeneous mix of breast tumors [7].TNBC generally has a poorer prognosis among patients with breast cancer [21].
ER, PR and HER2 are the important biologic markers used in targeted treatment of breast cancer [22].
Understanding of other biological characteristics of TNBC, the development of new therapeutical approaches and identification of new markers is necessary due to the lack of biological markers like ER, PR and HER2.CD44+, CD24-/low and ALDH1+ are the most consistently used biomarkers to identify the breast cancer stem cell groups [16][17].The clinical importance of ALDH1 in TNBC is a less investigated issue.The purpose of this study was to investigate the prognostic effect of the expression of aldehyde dehydrogenase-1 (ALDH1) in TNBC and its relationship with the clinico-pathological features

Materials and Methods
In this study we included 87 patients followed

Discussion
Breast cancer is a heterogeneous disease with a lot of histological special types showing different molecular, histologic and clinic features [15].We achieved a significant reduction in breast cancer mortality with the screening programs and treatment facilities in adjuvant treatment of early stage breast cancer.The mortality rates are being reduced even more by the use of targeted therapy.
TNBC accounts for 15% to 20% of breast cancers [3].Endocrine therapy and HER2-directed therapies are not used in the treatment of TNBC since it is characterized by the lack of biological markers like ER, PR and HER2 [23].TNBC generally has a poorer prognosis compared to patients with other breast cancer subtypes.Considerable effort has been made to develop new therapeutical approaches in TNBC [8].
The classical pathological variables such as tumor grade, lymph node status, and tumor size, are the most important prognostic factors in breast cancer.Ki67 status, tumor grade, lymphatic, perineural, vascular invasion are also independent prognostic factors that can affect the therapy choice [9,11].
Based on the diagnostic evaluation of suspected breast cancer one of the patients was diagnosed after physical examination, one during routine screening and all others (n:85) were suspected by their self-examination.These findings support the fact that TNBC will more likely present as an 'interval cancer' between two screenings.These findings also show that TNBC screening and diagnosis need to be improved [12][13][14].
In our study 14 patients (16.1%) received neoadjuvant therapy because of locally advanced disease, 59 patients (67.8%) received adjuvant therapy.DFS of patients receiving neoadjuvant therapy was statistically significant short than others(p=0.02,24 months DFS; %31.2 vs %80.5).This finding maybe reflective of locally advanced disease, but also specially inTNBC may suggest that neoadjuvant chemotherapy may have limited effect and delaying of the surgical treatment may affect the prognosis.
A total of 11 patients were found to be ALDH1-positive and this positivity doesn't seem to be statistically significant alone.ALDH1as a biomarker to identify the breast cancer stem cell groups that can lead to targeted therapies in breast cancer was not found to be a prognostic value alone.Further research combining with other biomarkers and with a greater number of patients is necessary to confirm the role of ALDH1 in TNBC.
immunohistochemically with ALDH1 (ALDH1a1: Biocare assay kit) then examined by light microscopy.The prognostic value of these clinical data and ALDH1 positivity were evaluated by determining disease-free survival and tumor characteristics from the clinicopathological data obtained from the files and paraffin blocks.Immunohistochemical staining ofALDH1 was classified as positive when tumor cells showed cytoplasmic positivity and negative when tumor cells showed cytoplasmic negativity.The prognostic value of these clinical data and ALDH1 positivity were evaluated by determining disease-free survival and tumor characteristics from the clinicopathological data obtained from the files and paraffin blocks.Among 87 files included in the present study, the metastatic ones and those who received neoadjuvant therapy but found to be metastatic before receiving adjuvant therapy were excluded.Statistical analyses include 71 patients.The DFS (disease-free survival) was defined as the time from the diagnosis to the date of breast-cancerderived relapse/metastasis.DFS for patients who received adjuvant therapy (month): (the date of relapse or last visit date for those without relapse -operation date)/30, for those who received neoadjuvant therapy (month): (the date of relapse or last visit date for those without relapse -operation date after neoadjuvant therapy)/30.
Kaplan-Meier technique, analyses of the prognostic factors and DFS were performed with the log-rank test.Multivariable analyses were conducted for the factors statistically significant in the Cox Proportional Hazards model.