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      Racial and Ethnic Differences in Breast Cancer Survival: Mediating Effect of Tumor Characteristics and Sociodemographic and Treatment Factors.

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          Abstract

          To evaluate the relationship between race/ethnicity and breast cancer-specific survival according to subtype and explore mediating factors.

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          Most cited references43

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          Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype.

          Basal-like breast cancer is associated with high grade, poor prognosis, and younger patient age. Clinically, a triple-negative phenotype definition [estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (HER)-2, all negative] is commonly used to identify such cases. EGFR and cytokeratin 5/6 are readily available positive markers of basal-like breast cancer applicable to standard pathology specimens. This study directly compares the prognostic significance between three- and five-biomarker surrogate panels to define intrinsic breast cancer subtypes, using a large clinically annotated series of breast tumors. Four thousand forty-six invasive breast cancers were assembled into tissue microarrays. All had staging, pathology, treatment, and outcome information; median follow-up was 12.5 years. Cox regression analyses and likelihood ratio tests compared the prognostic significance for breast cancer death-specific survival (BCSS) of the two immunohistochemical panels. Among 3,744 interpretable cases, 17% were basal using the triple-negative definition (10-year BCSS, 6 7%) and 9% were basal using the five-marker method (10-year BCSS, 62%). Likelihood ratio tests of multivariable Cox models including standard clinical variables show that the five-marker panel is significantly more prognostic than the three-marker panel. The poor prognosis of triple-negative phenotype is conferred almost entirely by those tumors positive for basal markers. Among triple-negative patients treated with adjuvant anthracycline-based chemotherapy, the additional positive basal markers identified a cohort of patients with significantly worse outcome. The expanded surrogate immunopanel of estrogen receptor, progesterone receptor, human HER-2, EGFR, and cytokeratin 5/6 provides a more specific definition of basal-like breast cancer that better predicts breast cancer survival.
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            Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade.

            A number of microarray studies have reported distinct molecular profiles of breast cancers (BC), such as basal-like, ErbB2-like, and two to three luminal-like subtypes. These were associated with different clinical outcomes. However, although the basal and the ErbB2 subtypes are repeatedly recognized, identification of estrogen receptor (ER) -positive subtypes has been inconsistent. Therefore, refinement of their molecular definition is needed. We have previously reported a gene expression grade index (GGI), which defines histologic grade based on gene expression profiles. Using this algorithm, we assigned ER-positive BC to either high-or low-genomic grade subgroups and compared these with previously reported ER-positive molecular classifications. As further validation, we classified 666 ER-positive samples into subtypes and assessed their clinical outcome. Two ER-positive molecular subgroups (high and low genomic grade) could be defined using the GGI. Despite tracking a single biologic pathway, these were highly comparable to the previously described luminal A and B classification and significantly correlated to the risk groups produced using the 21-gene recurrence score. The two subtypes were associated with statistically distinct clinical outcome in both systemically untreated and tamoxifen-treated populations. The use of genomic grade can identify two clinically distinct ER-positive molecular subtypes in a simple and highly reproducible manner across multiple data sets. This study emphasizes the important role of proliferation-related genes in predicting prognosis in ER-positive BC.
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              Revision of the American Joint Committee on Cancer staging system for breast cancer.

              To revise the American Joint Committee on Cancer staging system for breast carcinoma. A Breast Task Force submitted recommended changes and additions to the existing staging system that were (1) evidence-based and/or consistent with widespread clinical consensus about appropriate diagnostic and treatment standards and (2) useful for the uniform accrual of outcome information in national databases. Major changes included the following: size-based discrimination between micrometastases and isolated tumor cells; identifiers to indicate usage of innovative technical approaches; classification of lymph node status by number of involved axillary lymph nodes; and new classifications for metastasis to the infraclavicular, internal mammary, and supraclavicular lymph nodes. This revised staging system will be officially adopted for use in tumor registries in January 2003.
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                Author and article information

                Journal
                J. Clin. Oncol.
                Journal of clinical oncology : official journal of the American Society of Clinical Oncology
                American Society of Clinical Oncology (ASCO)
                1527-7755
                0732-183X
                Jul 10 2015
                : 33
                : 20
                Affiliations
                [1 ] Erica T. Warner and Rulla M. Tamimi, Harvard School of Public Health; Erica T. Warner, Rulla M. Tamimi, Melissa E. Hughes, Eric P. Winer, Jane C. Weeks, and Ann H. Partridge, Brigham and Women's Hospital; Melissa E. Hughes, Eric P. Winer, Jane C. Weeks, and Ann H. Partridge, Dana-Farber Cancer Institute, Boston, MA; Rebecca A. Ottesen and Joyce C. Niland, City of Hope Comprehensive Cancer Center, Duarte; Douglas W. Blayney, Stanford University Cancer Center, Palo Alto, CA; Yu-Ning Wong, Fox Chase Cancer Center, Philadelphia, PA; Stephen B. Edge, Baptist Cancer Center, Memphis, TN; and Richard L. Theriault, University of Texas MD Anderson Cancer Center, Houston, TX. ewarner@hsph.harvard.edu.
                [2 ] Erica T. Warner and Rulla M. Tamimi, Harvard School of Public Health; Erica T. Warner, Rulla M. Tamimi, Melissa E. Hughes, Eric P. Winer, Jane C. Weeks, and Ann H. Partridge, Brigham and Women's Hospital; Melissa E. Hughes, Eric P. Winer, Jane C. Weeks, and Ann H. Partridge, Dana-Farber Cancer Institute, Boston, MA; Rebecca A. Ottesen and Joyce C. Niland, City of Hope Comprehensive Cancer Center, Duarte; Douglas W. Blayney, Stanford University Cancer Center, Palo Alto, CA; Yu-Ning Wong, Fox Chase Cancer Center, Philadelphia, PA; Stephen B. Edge, Baptist Cancer Center, Memphis, TN; and Richard L. Theriault, University of Texas MD Anderson Cancer Center, Houston, TX.
                Article
                JCO.2014.57.1349
                10.1200/JCO.2014.57.1349
                4486344
                25964252
                77f02dd8-5f80-495a-9724-ff6b19e16b12
                History

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