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      Triple-negative breast cancers are increased in black women regardless of age or body mass index

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          Abstract

          Introduction

          We investigated clinical and pathologic features of breast cancers (BC) in an unselected series of patients diagnosed in a tertiary care hospital serving a diverse population. We focused on triple-negative (Tneg) tumours (oestrogen receptor (ER), progesterone receptor (PR) and HER2 negative), which are associated with poor prognosis.

          Methods

          We identified female patients with invasive BC diagnosed between 1998 and 2006, with data available on tumor grade, stage, ER, PR and HER2 status, and patient age, body mass index (BMI) and self-identified racial/ethnic group. We determined associations between patient and tumour characteristics using contingency tables and multivariate logistic regression.

          Results

          415 cases were identified. Patients were racially and ethnically diverse (born in 44 countries, 36% white, 43% black, 10% Hispanic and 11% other). 47% were obese (BMI > 30 kg/m2). 72% of tumours were ER+ and/or PR+, 20% were Tneg and 13% were HER2+. The odds of having a Tneg tumour were 3-fold higher (95% CI 1.6, 5.5; p = 0.0001) in black compared with white women. Tneg tumours were equally common in black women diagnosed before and after age 50 (31% vs 29%; p = NS), and who were obese and non-obese (29% vs 31%; p = NS). Considering all patients, as BMI increased, the proportion of Tneg tumours decreased (p = 0.08).

          Conclusions

          Black women of diverse background have 3-fold more Tneg tumours than non-black women, regardless of age and BMI. Other factors must determine tumour subtype. The higher prevalence of Tneg tumours in black women in all age and weight categories likely contributes to black women's unfavorable breast cancer prognosis.

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          Most cited references39

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          Prognostic markers in triple-negative breast cancer.

          Triple-negative breast cancer (estrogen receptor-negative, progesterone receptor-negative, and HER2-negative) is a high risk breast cancer that lacks the benefit of specific therapy that targets these proteins. In this study, the authors examined a large and well characterized series of invasive breast carcinoma (n = 1944) with a long-term clinical follow-up (median, 56 months) by using tissue microarray. The series were also stained with concurrent immunohistochemical prognostic panels (estrogen receptor, progesterone receptor, HER-2, androgen receptor, epidermal growth factor receptor (EGFR), P-cadherin, E-cadherin, and basal (CK5/6, CK14), and p53), to characterize this specific subgroup of breast cancer and to identify prognostic markers that can identify tumors with more aggressive behavior. Of informative cases, 16.3% were of the triple-negative phenotype. The majority of these tumors were grade 3, ductal/no-specific-type carcinomas. There were positive associations with larger size, pushing margins, poorer Nottingham Prognostic Index, development of recurrence and distant metastasis, and poorer outcome. In addition, associations were found with loss of expression of androgen receptor and E-cadherin, and positive expression of basal cytokeratins (basal phenotype), P-cadherin, p53, and EGFR. In all tumors, tumor size, lymph node stage, and androgen receptor were the most useful prognostic markers. In the lymph node-positive subgroup, both size and androgen receptor retained their prognostic significance. However, in the lymph node-negative tumors, basal phenotype was the sole prognostic marker identified in this subgroup. Other parameters including age, histological grade, tumor size, vascular invasion or other biomarkers included in the current study were not significant. The authors concluded that assessment of androgen receptor and basal phenotype, in addition to the established pathologic variables, mainly lymph node status and tumor size, can be used to select high-risk and low-risk patients at the time of primary surgery and can provide valuable information on treatment options in these triple-negative tumors. (c) 2006 American Cancer Society.
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            Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute's Surveillance, Epidemiology, and End Results database.

            Breast carcinomas in African-American patients appear to be more aggressive than in Caucasian patients due to multifactorial differences. The authors compiled pathology data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database regarding stage, histologic grade, and estrogen receptor (ER) expression in breast carcinomas diagnosed in 197,274 African-American and Caucasian patients between 1990 and 2000, and the same information, along with nuclear grade, Ki-67, c-erb-B2, and p53 expression, in 2230 African-American and Caucasian patients diagnosed at Thomas Jefferson University Hospital between 1995 and 2002. Immunohistochemical markers were assayed in paraffin-embedded, formalin-fixed tissue stained with hematoxylin and eosin using antibodies to these proteins, with differences in expression analyzed by the chisquare test. In both databases, more African-American patients presented with advanced stage tumors and higher histologic (P < .001) and nuclear grade (P < .001) than Caucasian patients. African-American patients had less ER positivity (51.9% vs 63.1%; P < .001) but significantly higher Ki-67 (42.4% vs 28.7%; P < .001) and p53 expression (19.4% vs 13.1%; P < .05) than Caucasian patients with all stages of disease. In addition, the basal or "triple-negative" breast cancer phenotype was more common in African-American patients than in Caucasian patients (20.8% vs 10.4%; P < .0001), and was associated with higher histologic and nuclear grade (P < .0001). African-American patients with breast carcinomas are more likely than Caucasian patients to present with tumors that are of a later stage and higher grade, with higher Ki-67 expression and more ER negativity, thereby highlighting a greater need for early screening among African-American women. Molecular studies that may explain these differences, and correlations with survival, have been proposed to identify therapeutic targets.
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              Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk.

              The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (CI): 0.96, 1.10) in premenopausal women and 1.07 (95% CI: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% CI: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% CI: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.
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                Author and article information

                Journal
                Breast Cancer Res
                Breast Cancer Research : BCR
                BioMed Central
                1465-5411
                1465-542X
                2009
                25 March 2009
                : 11
                : 2
                : R18
                Affiliations
                [1 ]Department of Medicine, Boston University Medical Center, 650 Albany Street, Boston, MA 02118, USA
                [2 ]Department of Epidemiology, Boston University School of Public Health, 715 Albany Street, Talbot Building, Boston, MA 02118, USA
                [3 ]Department of Pathology and Laboratory Medicine, Boston University Medical Center, 650 Albany Street, Boston, MA 02118, USA
                Article
                bcr2242
                10.1186/bcr2242
                2688946
                19320967
                8f538a3b-96e4-4aae-93f6-189166c304d3
                Copyright © 2009 Stead et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 October 2008
                : 19 November 2008
                : 17 February 2009
                : 25 March 2009
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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