Original contributionPrognostic value of the X-linked inhibitor of apoptosis protein for invasive ductal breast cancer with triple-negative phenotype☆
Introduction
Breast cancer remains a main leading cause of morbidity and mortality in women all over the world, especially in developing countries including China [1]. During the past several years, great progress has been achieved based on the gene expressions profile generated by DNA microarray analysis. As such, breast cancer can now be redefined into 5 molecular subtypes, each of which is associated with distinct clinical implications [2], [3]. Triple-negative breast cancers (TNBCs) are characterized by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and HER2/neu [4]. TNBCs account for 15% to 24% of all invasive ductal breast cancers of no specific type, are characterized by very aggressive biological behavior, and are associated with poor clinical prognoses compared with other types of cancer [5], [6]. Furthermore, it should be emphasized that TNBCs are composed of a heterogeneous group of tumors [6], [7]. Thus, the identification of tumor markers that allow the identification of patients at higher risk for invasive ductal breast cancer with triple-negative phenotype remains a research and clinical priority. At present, however, research on detecting factors that affect prognosis of invasive ductal TNBC has not been performed thoroughly.
Inhibitors of apoptotic proteins are a more recently described family of proteins that includes the X-linked inhibitor of apoptosis protein (XIAP), which acts by directly inhibiting caspases. There are little data about XIAP roles in invasive ductal breast cancer with triple-negative phenotype. Thus, the aim of this study is to evaluate the possible prognostic role of XIAP in invasive ductal breast cancer with triple-negative phenotype.
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Patients and tissues
Two hundred patients diagnosed with invasive ductal breast cancer between January 1997 and January 2004 at the Department of Pathology of Tianjin Medical University General Hospital were enrolled in this study. The study was approved by the ethics committees of Tianjin Medical University, and written informed consent was obtained from all participating patients. All patients had complete clinicopathologic information, including age, menopause status, tumor size, and number of axillary-positive
Patient and primary tumor characteristics
Patient and primary tumor characteristics are presented in Table 1. Among 200 patients diagnosed with invasive ductal breast cancer, 42 lacked ER, PR, and HER2 expression. All 42 patients were women with a mean age of 48.83 ± 9.59 years (range, 32-69 years); 23 (54.76%) patients were between the ages of 35 and 49 years, and 16 (38.10%) patients were aged more than 50 years. At the time of breast cancer surgery, 15 (35.71%) patients were postmenopausal and 27 (64.29%) were premenopausal.
Discussion
Breast cancer, the most common malignant solid tumor occurring in women, consists of a wide variety of histologic types with different clinical behaviors and outcomes. Current breast cancer histopathologic classification systems are based on several descriptive entities that are of prognostic significance. For a long time, traditional clinicopathologic factors such as lymph node status, tumor size, microvessel density, and histologic grade were considered to be the most useful prognostic
References (35)
- et al.
Molecular classifications of breast carcinoma with similar terminology and different definitions: are they the same?
Hum Pathol
(2008) - et al.
Impact of American Society of Clinical Oncology/College of American Pathologists guideline recommendations on HER2 interpretation in breast cancer
Hum Pathol
(2010) - et al.
The role of molecular analysis in breast cancer
Pathology
(2009) - et al.
XIAP: cell death regulation meets copper homeostasis
Arch Biochem Biophys
(2007) - et al.
Ki-67 as a prognostic molecular marker in routine clinical use in breast cancer patients
Breast
(2009) - et al.
Characteristics and prognosis for molecular breast cancer subtypes in Chinese women
J Surg Oncol
(2009) - et al.
Prognostic significance of molecular classification of breast invasive ductal carcinoma
Arch Gynecol Obstet
(2009) - et al.
Triple negative breast cancer: clinicopathological characteristics and treatment strategies
Breast Cancer
(2009) - et al.
Triple negative tumours: a critical review
Histopathology
(2008) - et al.
Triple-negative breast cancer—towards a new entity
Rev Med Chir Soc Med Nat Iasi
(2008)
Population differences in breast cancer severity
Pharmacogenomics
Molecular classification of breast carcinomas using tissue microarrays
Diagn Mol Pathol
High clusterin expression correlates with a poor outcome in stage II colorectal cancers
Cancer Epidemiol Biomarkers Prev
The predictive role of E-cadherin and androgen receptor on in vitro chemosensitivity in triple-negative breast cancer
Jpn J Clin Oncol
Prognostic and predictive factors of invasive breast cancer: update 2009
Pathologe
Breast cancer: new concepts in classification
Rev Bras Ginecol Obstet
Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity
Breast Cancer Res Treat
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2018, Journal of Biological ChemistryCitation Excerpt :Some family members, such as cIAP1, cIAP2, and XIAP, directly interact with and regulate caspases via the BIR domain, thus inhibiting apoptosis (35–38). These IAPs are attractive targets for tumor therapy because of their frequent overexpression in multiple human malignancies and their implications in tumor progression, treatment failure, and poor prognosis (39–45). Based on the IAP-binding tetrapeptides of second mitochondria-derived activator of caspases/direct IAP-binding protein with low pI (SMAC/DIABLO), many potent and cell-permeable peptidomimetic IAP antagonists (also known as SMAC mimetics) have been developed; some of these are under evaluation in clinical phase studies as antitumor drugs (32, 46, 47).
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Supported by the Tianjin Natural Science Foundation (06YFJMJC08000 and 09ZCZDSF04400) from Tianjin, PR China, and a science grant from Tianjin Medical University (2008KY06), Tianjin, PR China.
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These authors contributed equally to this work.