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      The prevalence of estrogen receptor-negative breast cancer in Ethiopia

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          Abstract

          Background

          In contrast with breast cancers (BCs) in other parts of the world, most previous studies reported that the majority of BCs in sub-Saharan Africa are estrogen-receptor (ER) negative. However, a recent study using the US SEER database showed that the proportion of ER-negative BC is comparable between US-born blacks and West-African born blacks but substantially lower in East African-born blacks, with over 74% of patients Ethiopians or Eritreans. In this paper, we provide the first report on the proportion of ER-negative BC in Ethiopia, and the relation to progesterone-receptor (PgR) status.

          Methods

          We analysed 352 female patients with ER results available out of 1208 consecutive female BC patients treated at Addis Ababa-University Hospital, Ethiopia, from June 2005 through December 2010. The influences of age, stage, and histology on the probability of ER-negative tumours were assessed by a log-linear regression model.

          Results

          Of the 352 patients, only 35% were ER-negative. The proportion of ER-negative tumours decreased with advancing age at diagnosis and was not affected by histology or stage. For age, the proportion decreased by 6% for each additional 5 years (stage-adjusted prevalence ratio PR = 0.94, 95% CI: 0.89–1.00). About 31% were ER- and PgR-negative, and 69% were ER- and/or PgR-positive.

          Conclusions

          Contrary to most previous reports in other parts of sub-Saharan Africa, the majority of patients in Ethiopia are ER-positive rather than ER-negative. These findings are in line with low proportions of ER-negative BCs from East African immigrants within the SEER database, and they have clinical implications for management of BC patients in Ethiopia and other parts of sub-Saharan Africa where ER-status is not ascertained as part of routine management of the disease. Since the majority of patients showed ER-positive BC, Tamoxifen-therapy should be given to all patients even with unknown ER status.

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          Most cited references24

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          Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007.

          The 10th St Gallen (Switzerland) expert consensus meeting in March 2007 refined and extended a target-oriented approach to adjuvant systemic therapy of early breast cancer. Target definition is inextricably intertwined with the availability of target-specific therapeutic agents. Since 2005, the presence of HER2 on the cell surface has been used as an effective target for trastuzumab much as steroid hormone receptors are targets for endocrine therapies. An expert Panel reaffirmed the primary importance of determining endocrine responsiveness of the cancer as a first approach to selecting systemic therapy. Three categories were acknowledged: highly endocrine responsive, incompletely endocrine responsive and endocrine non-responsive. The Panel accepted HER2-positivity to assign trastuzumab, and noted that adjuvant trastuzumab has only been assessed together with chemotherapy. They largely endorsed previous definitions of risk categories. While recognizing the existence of several molecularly-based tools for risk stratification, the Panel preferred to recommend the use of high-quality standard histopathological assessment for both risk allocation and target identification. Chemotherapy, although largely lacking specific target information, is the only option in cases which are both endocrine receptor-negative and HER2-negative. Chemotherapy is conventionally given with or preceding trastuzumab for patients with HER2-positive disease, and may be used for patients with endocrine responsive disease in cases where the sufficiency of endocrine therapy alone is uncertain. Recommendations are provided not as specific therapy guidelines but rather as a general guidance emphasizing main principles for tailoring therapeutic choice.
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            Population differences in breast cancer: survey in indigenous African women reveals over-representation of triple-negative breast cancer.

            Compared with white women, black women experience a disproportionate burden of aggressive breast cancer for reasons that remain unknown and understudied. In the first study of its kind, we determined the distribution of molecular subtypes of invasive breast tumors in indigenous black women in West Africa. The study comprised 507 patients diagnosed with breast cancer between 1996 and 2007 at six geographic regions in Nigeria and Senegal. Formalin-fixed and paraffin-embedded sections were constructed into tissue microarrays and immunostained with 15 antibodies. Five molecular subtypes were determined, and hierarchical cluster analysis was conducted to explore subgroups for unclassified cases. The mean (+/- standard deviation) age of 378 patients in the first cohort was 44.8 +/- 11.8 years, with the majority of women presenting with large (4.4 +/- 2.0 cm) high-grade tumors (83%) in advanced stages (72% node positive). The proportions of estrogen receptor (ER) -positive, progesterone receptor-positive, and human epidermal growth factor receptor 2 (HER2) -positive tumors were 24%, 20%, and 17%, respectively. Triple negativity for these markers was predominant, including basal-like (27%) and unclassified subtype (28%). Other subtypes were luminal A (27%), luminal B (2%), and HER2 positive/ER negative (15%). The findings were replicated in the second cohort of 129 patients. The unclassified cases could be grouped into a bad prognosis branch, with expression of vascular endothelial growth factor, B-cell lymphoma extra-large protein, and Cyclin E, and a good prognosis branch, with expression of B-cell lymphoma protein 2 and Cyclin D1. These findings underscore the urgent need for research into the etiology and treatment of the aggressive molecular subtypes that disproportionately affect young women in the African diaspora.
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              African ancestry and higher prevalence of triple-negative breast cancer: findings from an international study.

              The study of breast cancer in women with African ancestry offers the promise of identifying markers for risk assessment and treatment of triple-negative disease. African American and white American women with invasive cancer diagnosed at the Henry Ford Health System comprised the primary study population, and Ghanaian patients diagnosed and/or treated at the Komfo Anokye Teaching Hospital in Kumasi, Ghana constituted the comparison group. Formalin-fixed, paraffin-embedded specimens were transported to the University of Michigan for histopathology confirmation, and assessment of estrogen and progesterone receptors and HER-2/neu expression. The study population included 1008 white Americans, 581 African Americans, and 75 Ghanaians. Mean age at diagnosis was 48.0 years for Ghanaian, 60.8 years for African American, and 62.4 for white American cases (P=.002). Proportions of Ghanaian, African American, and white American cases with estrogen receptor-negative tumors were 76%, 36%, and 22%, respectively (P<.001), and proportions with triple-negative disease were 82%, 26%, and 16%, respectively (P<.001). All Ghanaian cases were palpable, locally advanced cancers; 57 (76%) were grade 3. A total of 147 American women were diagnosed as stage III or IV; of these, 67.5% (n=46) of African Americans and 44.6% (n=29) of white Americans were grade 3. Among palpable, grade 3 cancers, Ghanaians had the highest prevalence of triple-negative tumors (82.2%), followed by African Americans (32.8%) and white Americans (10.2%). Our study demonstrates progressively increasing frequency of estrogen receptor-negative and triple-negative tumors among breast cancer patients with white American, African American, and Ghanaian/African backgrounds. This pattern indicates a need for additional investigations correlating the extent of African ancestry and high-risk breast cancer subtypes. Copyright © 2010 American Cancer Society.
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                Author and article information

                Contributors
                eva.kantelhardt@uk-halle.de
                mathewosassefa80@hotmail.com
                aynalemab@yahoo.co.uk
                tigeneh@yahoo.com
                Ahmedin.Jemal@cancer.org
                Martina.vetter@uk-halle.de
                erdme.knauf@web.de
                Anne.Reeler@axiosint.com
                bsolomond@ethionet.et
                Christoph.thomssen@medizin.uni-halle.de
                Andreas.stang@uk-halle.de
                tufa.gemechu@yahoo.com
                pietro.trocchi@uk-halle.de
                yonasbtsion@yahoo.com
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                29 November 2014
                29 November 2014
                2014
                : 14
                : 1
                : 895
                Affiliations
                [ ]Department of Gynecology and Institute of Clinical Epidemiology, Martin-Luther-University, Ernst-Grube Str. 40, 06097 Halle an der Saale, Germany
                [ ]Radiotherapy Center, Addis-Ababa-University, Addis Ababa, Ethiopia
                [ ]American Cancer Society, Atlanta, USA
                [ ]Department of Gynecology, Martin-Luther-University, Halle an der Saale, Germany
                [ ]Axios International, Paris, France
                [ ]Institute of Clinical Epidemiology, Martin-Luther-University, Halle an der Saale, Germany
                [ ]Department of Pathology, Addis-Ababa-University, Addis Ababa, Ethiopia
                [ ]Department of Epidemiology, Boston University, School of Public Health, Boston, MA USA
                Article
                5062
                10.1186/1471-2407-14-895
                4258259
                25433805
                3a6af62a-dfa6-4986-8632-07209c56073b
                © Kantelhardt et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 12 June 2014
                : 20 November 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Oncology & Radiotherapy
                breast neoplasms,africa,ethiopia,prognostic factors
                Oncology & Radiotherapy
                breast neoplasms, africa, ethiopia, prognostic factors

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