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      Stage at diagnosis and stage-specific survival of breast cancer in Latin America and the Caribbean: A systematic review and meta-analysis

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          Abstract

          Background

          Female breast cancer is the most common cancer in Latin American and Caribbean (LAC) countries and is the leading cause of cancer deaths. The high mortality-to-incidence ratio in the regions is associated with mainly the high proportion of advanced stage diagnosis, and also to inadequate access to health care. In this study we aimed to systematically review the proportion of advanced stage (III-IV) at diagnosis (p as) and the five-year stage-specific survival estimates of breast cancer in LAC countries.

          Methods

          We searched MEDLINE, Embase, and LILACS (Latin American and Caribbean Health Science Literature) to identify studies, in any language, indexed before Nov 5, 2018. We also conducted manual search by reviewing citations of papers found. p as was summarized by random effects model meta-analysis, and meta-regression analysis to identify sources of variation. Stage-specific survival probabilities were described as provided by study authors, as it was not possible to conduct meta-analysis. PROSPERO CRD42017052493.

          Results

          For p as we included 63 studies, 13 of which population-based, from 22 countries comprising 221,255 women diagnosed from 1966 to 2017. The distribution of patients by stage varied greatly in LAC (p as 40.8%, 95%CI 37.0% to 44.6%; I 2 = 99%; p<0.0001). The heterogeneity was not explained by any variable included in the meta-regression. There was no difference in p as among the Caribbean (p as 43.0%, 95%CI 33.1% to 53.6%), Central America (p as 47.0%, 95%CI 40.4% to 53.8%) and South America (p as 37.7%, 95%CI 33.1% to 42.5%) regions. For 5-year stage-specific survival we included 37 studies, comprising 28,988 women from ten countries. Seven of these studies were included also for p as. Since we were unable to adjust for age, comparability between countries and regions was hampered, and as expected, the results varied widely from study to study.

          Conclusions

          LAC countries should look to address concerns with early detection and diagnosis of breast cancer, and wherever viable implement screening programs and to provide timely treatment.

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          Most cited references32

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          Delays in Breast Cancer Detection and Treatment in Developing Countries

          Breast cancer is the most common cancer in women in both developed and developing countries and the second most common cancer in the world. Developing countries are increasingly adopting a Western lifestyle, such as changes in diet and delayed first childbirth, lower parity, and shorter periods of breastfeeding, which are important determinants of a higher incidence of breast cancer among those regions. Low- and middle-income countries (LMICs) represent most of the countries with the highest mortality rates, ranging from 40% to 60%. Furthermore, developing countries account for scarce survival data, and the few data available coincide with the observed incidence and mortality differences. Five-year survival rates for breast cancer are much worse for LMICs countries such as Brazil, India, and Algeria in comparison with the United States and Sweden. Paucity of early detection programs explain these poor survival rates, which results in a high proportion of women presenting with late-stage disease, along with lack of adequate diagnosis and treatment facilities. Emphasis is urgently needed on health education, to promote early diagnosis of breast cancer, highlighting the importance of creating more public facilities that provide treatment, which are key components for the improvement in breast cancer care in developing countries.
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            Breast cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK, 2000-2007: a population-based study

            Background: We investigate whether differences in breast cancer survival in six high-income countries can be explained by differences in stage at diagnosis using routine data from population-based cancer registries. Methods: We analysed the data on 257 362 women diagnosed with breast cancer during 2000–7 and registered in 13 population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Flexible parametric hazard models were used to estimate net survival and the excess hazard of dying from breast cancer up to 3 years after diagnosis. Results: Age-standardised 3-year net survival was 87–89% in the UK and Denmark, and 91–94% in the other four countries. Stage at diagnosis was relatively advanced in Denmark: only 30% of women had Tumour, Nodes, Metastasis (TNM) stage I disease, compared with 42–45% elsewhere. Women in the UK had low survival for TNM stage III–IV disease compared with other countries. Conclusion: International differences in breast cancer survival are partly explained by differences in stage at diagnosis, and partly by differences in stage-specific survival. Low overall survival arises if the stage distribution is adverse (e.g. Denmark) but stage-specific survival is normal; or if the stage distribution is typical but stage-specific survival is low (e.g. UK). International differences in staging diagnostics and stage-specific cancer therapies should be investigated.
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              Delay in Breast Cancer: Implications for Stage at Diagnosis and Survival

              Lee Caplan (2014)
              Breast cancer continues to be a disease with tremendous public health significance. Primary prevention of breast cancer is still not available, so efforts to promote early detection continue to be the major focus in fighting breast cancer. Since early detection is associated with decreased mortality, one would think that it is important to minimize delays in detection and diagnosis. There are two major types of delay. Patient delay is delay in seeking medical attention after self-discovering a potential breast cancer symptom. System delay is delay within the health care system in getting appointments, scheduling diagnostic tests, receiving a definitive diagnosis, and initiating therapy. Earlier studies of the consequences of delay on prognosis tended to show that increased delay is associated with more advanced stage cancers at diagnosis, thus resulting in poorer chances for survival. More recent studies have had mixed results, with some studies showing increased survival with longer delays. One hypothesis is that diagnostic difficulties could perhaps account for this survival paradox. A rapidly growing lump may suggest cancer to both doctors and patients, while a slow growing lump or other symptoms could be less obvious to them. If this is the case, then the shorter delays would be seen with the more aggressive tumors for which the prognosis is worse leading to reduced survival. It seems logical that a tumor that is more advanced at diagnosis would lead to shorter survival but the several counter-intuitive studies in this review show that it is dangerous to make assumptions.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: Methodology
                Role: Formal analysisRole: Methodology
                Role: ConceptualizationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 October 2019
                2019
                : 14
                : 10
                : e0224012
                Affiliations
                [1 ] Programa de Pós-Graduação em Saúde Pública, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
                [2 ] SUS Collaborating Centre for Technology Assessment and Excellence in Health, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
                [3 ] Divisão de Pesquisa Populacional, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, Rio de Janeiro, Brazil
                [4 ] Programa de Pós-Graduação em Medicamentos e Assistência Farmacêutica, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
                [5 ] Strathclyde Institute of Pharmacy and Biomedical Sciences, Strathclyde University, Glasgow, Scotland
                [6 ] Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, Karolinska Institutet, Huddinge, Sweden
                [7 ] Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
                Leibniz Institute for Prevention Research and Epidemiology BIPS, GERMANY
                Author notes

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

                Author information
                http://orcid.org/0000-0002-8921-515X
                Article
                PONE-D-18-35785
                10.1371/journal.pone.0224012
                6799865
                31618268
                25c7e4fd-1601-4a5b-9ac9-f83c4a94ceed
                © 2019 de Lemos et al

                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.

                History
                : 17 December 2018
                : 3 October 2019
                Page count
                Figures: 4, Tables: 2, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100002322, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004901, Fundação de Amparo à Pesquisa do Estado de Minas Gerais;
                Award Recipient :
                LLPL received a PhD scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – https://www.capes.gov.br/) (award number not provided). MLC received scholarships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – http://www.cnpq.br/) (award number not provided) and from Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG – https://fapemig.br/) (award number not provided). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Breast Tumors
                Breast Cancer
                People and places
                Geographical locations
                North America
                Caribbean
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Metaanalysis
                Physical Sciences
                Mathematics
                Statistics
                Statistical Methods
                Metaanalysis
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                People and places
                Population groupings
                Ethnicities
                Latin American people
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Cancer Screening
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Cancer Screening
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

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