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      Distinct outcomes in patients with different molecular subtypes of inflammatory breast cancer

      research-article
      , MD, , MS, , MD, , MS, , MS, , MD, , MS, , MD
      Saudi Medical Journal
      Saudi Medical Journal

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          Abstract

          Objectives:

          To determine the outcome of patients with luminal A, luminal B, human epidermal growth factor receptor-2 (HER-2) positive, and triple negative molecular subtypes of inflammatory breast cancer (IBC) using a retrospective analysis.

          Methods:

          This study was conducted between February 2004 and February 2010 in 3 different hospitals in China. The clinical outcomes, pathological features, and treatment strategies were analyzed in 67 cases of IBC without distant metastases. A chi-square test and one-way ANOVA were used to assess outcomes between different subtypes. Overall survival (OS) was analyzed using the Kaplan-Meier method and multivariate analysis was conducted using the Cox regression model.

          Results:

          The 2-year OS rate was 55% for the entire cohort. Median OS time among patients with luminal A was 35 months, luminal B was 30 months, HER-2 positive was 24 months, and triple negative subtypes was 20 months, and they were significantly different from each other ( p=0.001). Using multivariate analysis, luminal A had 76% ( p=0.037), luminal B had 54% ( p=0.048), and HER-2 positive subtypes had 47% ( p=0.032) decreased risk of death compared with the triple negative subtype. Furthermore, elevated Ki-67 labeling was associated with increased risk of death, while the surgical treatment significantly improved patient survival.

          Conclusion:

          Breast cancer subtypes are associated with distinct outcomes in IBC patients. Patients that presented with triple negative IBC had poorer outcome than luminal A, luminal B, and HER-2 subtypes. These results indicate that IBC is a heterogeneous disease similar to the conventional breast cancer.

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          Most cited references19

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          International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment.

          Inflammatory breast cancer (IBC) represents the most aggressive presentation of breast cancer. Women diagnosed with IBC typically have a poorer prognosis compared with those diagnosed with non-IBC tumors. Recommendations and guidelines published to date on the diagnosis, management, and follow-up of women with breast cancer have focused primarily on non-IBC tumors. Establishing a minimum standard for clinical diagnosis and treatment of IBC is needed. Recognizing IBC to be a distinct entity, a group of international experts met in December 2008 at the First International Conference on Inflammatory Breast Cancer to develop guidelines for the management of IBC. The panel of leading IBC experts formed a consensus on the minimum requirements to accurately diagnose IBC, supported by pathological confirmation. In addition, the panel emphasized a multimodality approach of systemic chemotherapy, surgery, and radiation therapy. The goal of these guidelines, based on an expert consensus after careful review of published data, is to help the clinical diagnosis of this rare disease and to standardize management of IBC among treating physicians in both the academic and community settings.
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            Uncovering the molecular secrets of inflammatory breast cancer biology: an integrated analysis of three distinct affymetrix gene expression datasets.

            Inflammatory breast cancer (IBC) is a poorly characterized form of breast cancer. So far, the results of expression profiling in IBC are inconclusive due to various reasons including limited sample size. Here, we present the integration of three Affymetrix expression datasets collected through the World IBC Consortium allowing us to interrogate the molecular profile of IBC using the largest series of IBC samples ever reported. Affymetrix profiles (HGU133-series) from 137 patients with IBC and 252 patients with non-IBC (nIBC) were analyzed using unsupervised and supervised techniques. Samples were classified according to the molecular subtypes using the PAM50-algorithm. Regression models were used to delineate IBC-specific and molecular subtype-independent changes in gene expression, pathway, and transcription factor activation. Four robust IBC-sample clusters were identified, associated with the different molecular subtypes (P<0.001), all of which were identified in IBC with a similar prevalence as in nIBC, except for the luminal A subtype (19% vs. 42%; P<0.001) and the HER2-enriched subtype (22% vs. 9%; P<0.001). Supervised analysis identified and validated an IBC-specific, molecular subtype-independent 79-gene signature, which held independent prognostic value in a series of 871 nIBCs. Functional analysis revealed attenuated TGF-β signaling in IBC. We show that IBC is transcriptionally heterogeneous and that all molecular subtypes described in nIBC are detectable in IBC, albeit with a different frequency. The molecular profile of IBC, bearing molecular traits of aggressive breast tumor biology, shows attenuation of TGF-β signaling, potentially explaining the metastatic potential of IBC tumor cells in an unexpected manner. ©2013 AACR.
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              Triple-negative subtype predicts poor overall survival and high locoregional relapse in inflammatory breast cancer.

              Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC. We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989-2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER(+) (ER(+)/PR(+) and HER-2-; n = 105), ER(+)HER-2(+) (ER(+)/PR(+) and HER-2(+); n = 37), HER-2(+) (ER(-)/PR(-) and HER-2(+); n = 83), or triple-negative (TN) (ER(-)PR(-)HER-2(-); n = 91). Kaplan-Meier and Cox proportional hazards methods were used to assess LRR, DR, and OS rates and their associations with prognostic factors. The median age was 50 years (range, 24-83 years). The median follow-up time and median OS time for all patients were both 33 months. The 5-year actuarial OS rates were 58.7% for the entire cohort, 69.7% for ER(+) patients, 73.5% for ER(+)HER-2(+) patients, 54.0% for HER=2(+) patients, and 42.7% for TN patients (p < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%, respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%, 28.8%, 50.1%, 52.1%, and 56.7%, respectively (p < .001). OS and LRR rates were worse for TN patients than for any other subgroup (p < .0001-.03). TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype.
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                Author and article information

                Journal
                Saudi Med J
                Saudi Med J
                SaudiMedJ
                Saudi Medical Journal
                Saudi Medical Journal (Saudi Arabia )
                0379-5284
                1658-3175
                2014
                : 35
                : 11
                : 1324-1330
                Affiliations
                [1] From the Departments of Breast Surgery (Zhou, Guo, Ou, Hai, Tang), and Urology (Yan), Xiangya Hospital, Central South University, and the Department of Breast and Thyroid Surgery (Zhang), Hunan Provincial People's Hospital, and the Department of Breast Surgery (Wu), Hunan Provincial Tumor Hospital, Changsha, Hunan, China.
                Author notes
                Address correspondence and reprint request to: Prof. Lili Tang, Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. Tel. +86 (371) 89753516. Fax. +86 (134) 67508520. E-mail: tlli77@ 123456medmail.com.cn / tanglili77@ 123456163.com
                Article
                SaudiMedJ-35-1324
                4362150
                25399208
                ead581f1-23f4-42e9-a765-58b89c2241ab
                Copyright: © Saudi Medical Journal

                Saudi Medical Journal is an Open Access journal and articles published are distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC). Readers may copy, distribute, and display the work for non-commercial purposes with the proper citation of the original work.

                History
                : 08 May 2014
                : 15 September 2014
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