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Elevated Levels of Serum Tumor Markers CEA and CA15-3 Are Prognostic Parameters for Different Molecular Subtypes of Breast Cancer

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      Background & Aims

      The utility of measuring carcinoembryonic antigen(CEA) and cancer antigen 15-3 (CA15-3) levels in patients with breast cancer remains controversial. The present study aims to investigate the prognostic value of preoperative serum CEA and CA15-3 levels in breast cancer patients.


      Serum preoperative CEA and CA 15-3 concentration levels were measured in a total of 432 breast cancer patients. The association of tumor markers levels with clinicopathological parameters and outcomes were analyzed.


      Elevated serum levels of CEA and CA15-3 were identified in 47 (10.9%) and 60(13.9%) patients, respectively. Larger tumor size, advanced axillary lymph nodal and TNM stage exhibited higher proportion of elevated CEA and CA15-3 levels. The elevation of CEA levels was significantly greater in patients with HER2 positive tumors, and the elevation of CA15-3 levels was significantly greater in ER negative breast patients. Univariate and multivariate Cox’s regression analysis revealed that elevated preoperative CEA and CA 15-3 levels were independent prognostic factors for DFS and OS. When considering the combination of both markers levels, patients with both elevated markers presented the worst survival. Independent prognostic significance of elevated preoperative serum CEA and CA15-3 levels were reconfirmed in Luminal B breast cancer.


      Preoperative serum levels of CEA and CA15-3 are independent prognostic parameters for breast cancer.

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      Most cited references 29

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      Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011

      The 12th St Gallen International Breast Cancer Conference (2011) Expert Panel adopted a new approach to the classification of patients for therapeutic purposes based on the recognition of intrinsic biological subtypes within the breast cancer spectrum. For practical purposes, these subtypes may be approximated using clinicopathological rather than gene expression array criteria. In general, systemic therapy recommendations follow the subtype classification. Thus, ‘Luminal A’ disease generally requires only endocrine therapy, which also forms part of the treatment of the ‘Luminal B’ subtype. Chemotherapy is considered indicated for most patients with ‘Luminal B', ‘Human Epidermal growth factor Receptor 2 (HER2) positive’, and ‘Triple negative (ductal)’ disease, with the addition of trastuzumab in ‘HER2 positive’ disease. Progress was also noted in defining better tolerated local therapies in selected cases without loss of efficacy, such as accelerated radiation therapy and the omission of axillary dissection under defined circumstances. Broad treatment recommendations are presented, recognizing that detailed treatment decisions need to consider disease extent, host factors, patient preferences, and social and economic constraints.
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        Breast cancer statistics, 2013.

        In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 232,340 new cases of invasive breast cancer and 39,620 breast cancer deaths are expected to occur among US women in 2013. One in 8 women in the United States will develop breast cancer in her lifetime. Breast cancer incidence rates increased slightly among African American women; decreased among Hispanic women; and were stable among whites, Asian Americans/Pacific Islanders, and American Indians/Alaska Natives from 2006 to 2010. Historically, white women have had the highest breast cancer incidence rates among women aged 40 years and older; however, incidence rates are converging among white and African American women, particularly among women aged 50 years to 59 years. Incidence rates increased for estrogen receptor-positive breast cancers in the youngest white women, Hispanic women aged 60 years to 69 years, and all but the oldest African American women. In contrast, estrogen receptor-negative breast cancers declined among most age and racial/ethnic groups. These divergent trends may reflect etiologic heterogeneity and the differing effects of some factors, such as obesity and parity, on risk by tumor subtype. Since 1990, breast cancer death rates have dropped by 34% and this decrease was evident in all racial/ethnic groups except American Indians/Alaska Natives. Nevertheless, survival disparities persist by race/ethnicity, with African American women having the poorest breast cancer survival of any racial/ethnic group. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population. © 2013 American Cancer Society, Inc.
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          American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer.

          To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast cancer. For the 2007 update, an Update Committee composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of MEDLINE and the Cochrane Collaboration Library were performed. The Update Committee's literature review focused attention on available systematic reviews and meta-analyses of published tumor marker studies. In general, significant health outcomes (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used for making recommendations. Recommendations and Thirteen categories of breast tumor markers were considered, six of which were new for the guideline. The following categories showed evidence of clinical utility and were recommended for use in practice: CA 15-3, CA 27.29, carcinoembryonic antigen, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, urokinase plasminogen activator, plasminogen activator inhibitor 1, and certain multiparameter gene expression assays. Not all applications for these markers were supported, however. The following categories demonstrated insufficient evidence to support routine use in clinical practice: DNA/ploidy by flow cytometry, p53, cathepsin D, cyclin E, proteomics, certain multiparameter assays, detection of bone marrow micrometastases, and circulating tumor cells.

            Author and article information

            [1 ]Department of Breast oncology, The Affiliated Cancer Hospital Of Zhengzhou University, Zhengzhou, China
            [2 ]He’nan Province Tumor Hospital, Zhengzhou, China
            University of Nebraska Medical Center, UNITED STATES
            Author notes

            Competing Interests: The authors have declared that no competing interests exist.

            Conceived and designed the experiments: YS HL. Performed the experiments: YS XS. Analyzed the data: YS XS. Contributed reagents/materials/analysis tools: YS YH CL. Wrote the paper: YS HL.

            Role: Editor
            PLoS One
            PLoS ONE
            PLoS ONE
            Public Library of Science (San Francisco, CA USA )
            24 July 2015
            : 10
            : 7
            26207909 4514648 10.1371/journal.pone.0133830 PONE-D-14-58521

            This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

            Figures: 2, Tables: 3, Pages: 11
            This work was supported by the key scientific and technological projects of Science and Technology Department of Henan Province (No.122102310535).
            Research Article
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