Health Services, Socioeconomic Indicators, and Primary Care Coverage in Mortality by Lower Genital Tract and Breast Neoplasias in Brazilian Women during Reproductive and Non-Reproductive Periods

Round 1

Reviewer 1 Report

n this article, the authors collected a large amount of data to investigate the relationship between health services, socioeconomic indicators, and primary health care coverage and in mortality from neoplasms of lower genital tract and breast in Brazilian women during reproductive and non-reproductive periods. They show that primary health care coverage and health service indicators were not associated with breast cancer and female lower reproductive tract mortality, whether in reproductive or non reproductive periods, the mortality of breast and lower genital tract in reproductive women was related to income, while that of non reproductive breast and lower genital tract was related to education level However, several issues need to be considered to improve the manuscript.

Comments:

1. Though the manuscript is mostly written well, there are still a lot of grammar mistakes in the text, and the language also needs to be more fluent. Please carefully examine and revise.
2. References were in the format specified by International Journal of environmental research and public health.
3. L146 should be at the back of Figure 1.
4. In this paper, we do not see the reference 5.
5. In the discussion section, the author needs to further discuss the impact of income on breast and lower reproductive tract mortality of reproductive women, and the possible reasons why education level affects breast and lower reproductive tract mortality of non reproductive women.

Author Response

Dear Editor,

We are grateful for the considerations about our manuscript, "Health Services, Socioeconomic Indicators and Primary Care Coverage in The Mortality by Lower Genital Tract and Breast Neoplasias in Brazilian Women During the Reproductive and Non-Reproductive Periods" (Manuscript ID: ijerph-860766), submitted to International Journal of Environmental Research and Public Health (IJERPH).

This response letter contains a point-by-point reply to the peer reviewer’s comments, outlining the changes we have made.

Reviewer #1

In this article, the authors collected a large amount of data to investigate the relationship between health services, socioeconomic indicators, and primary health care coverage and in mortality from neoplasms of lower genital tract and breast in Brazilian women during reproductive and non-reproductive periods. They show that primary health care coverage and health service indicators were not associated with breast cancer and female lower reproductive tract mortality, whether in reproductive or non reproductive periods, the mortality of breast and lower genital tract in reproductive women was related to income, while that of non reproductive breast and lower genital tract was related to education level However, several issues need to be considered to improve the manuscript.

Comment 1: Though the manuscript is mostly written well, there are still a lot of grammar mistakes in the text, and the language also needs to be more fluent. Please carefully examine and revise.

After the completion of all reviews, the authors undertake to send the manuscript to a Platform specialized in the translation of articles for scientific journals, for correction of English. The time required for this correction is 3 working days.

Comment 2: References were in the format specified by International Journal of environmental research and public health.

Answer: Thanks, we really appreciate the comment. The new references added are also in the format specified by International Journal of environmental research and public health.

Comment 3: L146 should be at the back of Figure 1.

Answer: Thanks for the comment, we made the change and put the Figure 1 and the following paragraph after the Table 4

“There was no sigficant correlation between primary care coverage and mortality from neoplasms of the lower genital tract and breast according to reproductive periods (r = -0.31; p=0.110 for the non-reproductive period group and r = -0.08; p = 0.669 for the reproductive period group) (figure 1)”

This paragraph and Table 4 were changed to L195-201

Comment 4: In this paper, we do not see the reference 5.

Answer: Thanks for the comment, and we apologize for the mistake. We correct in the following paragraph in L41:

“Breast cancer is the most frequent type of cancer and the leading cause of death in women in developed and developing countries. Cervical cancer is the second most common cancer in the female genital tract [1,2]. In Brazil, other neoplasms of the female lower tract standout such as uterine body cancer, which is currently the third most prevalent; ovarian cancer, which is now the fourth most incident [3,4], and vulvar cancer, which is the fifth most common malignancy of the female lower genital tract [4-6].”

This paragraph is in L36-41

Comment 5: In the discussion section, the author needs to further discuss the impact of income on breast and lower reproductive tract mortality of reproductive women, and the possible reasons why education level affects breast and lower reproductive tract mortality of non-reproductive women.

Answer: Thanks for the comment, and we add the following paragraphs in the discussion section:

“The PHC coverage in Brazil has increased throughout the national territory, mainly after 2010 with an increase in the screening for cervical and breast cancer. However, there are still socioeconomic inequalities, which affect access to health care, or delay the screening of the main causes of cancer in the most vulnerable populations, and therefore its influence on reducing mortality is not yet significant [11].”

This paragraph is in L208-212

“Socioeconomic factors such as income inequality and education level are among the most important social indicators and its’ impact on breast and lower genital tract mortality were analyzed on this study. It is well established that low-income people are at increased risk of an array of adverse health outcomes and more likely to die prematurely [33].”

This paragraph is in L273-276

“Regions with the highest rates of social inequality and the lowest levels of human development presented the highest standardized mortality rates for cervical cancer, without a relationship with the distribution of health services offered to the population in a recent publication [39].”

This paragraph is in L297-299

“Regarding to breast cancer, literature demonstrate that low socioeconomic status is associated with increased risk of aggressive premenopausal breast cancers as well as late stage of diagnosis and poorer survival [43], and endorses the findings of this study.

This information largely impacts breast cancer care in Brazil since the country shows a significant upward trend on mortality from breast cancer among women 20–49 years [44].

However, the improvement in the distribution of financial income and living standards in developing countries has been accompanied by an increase in breast cancer incidence and mortality in women, who have adopted new habits and living conditions, exposing themselves to a more significant number of risk factors that can trigger the disease [45,46]. It is known that several factors that influence hormonal status (e.g., age at first child birth) or are markers of change in hormonal status (e.g., age at menarche and age at menopause) are associated with the risk of breast cancer [47].”

These paragraphs are in L305-315

“In Brazil there is an increase in nulliparous women, a low fertility rate and the postponement of pregnancy to an older age in recent decades [48].

This is due to the professional investment and seeking better living conditions, being an important association for the development of breast cancer [49] and can possibly illustrate the negative impact of more years of study on the mortality of non-reproductive women.”

These paragraphs are in L323-327

“Also, it is known that the implementation of effective programs for cervical cancer prevention and control through the realization of regular and timely cytopathologic tests in asymptomatic women enables the prevention and early oncologic diagnosis, minimizing cervical cancer mortality in the country [50] and that availability may not be possible in low income areas.”

This paragraph is in L335-338

We are grateful for the considerations about our manuscript

Best regards. 

Author Response File: Author Response.pdf

Reviewer 2 Report

Author Response

Dear Editor,

We are grateful for the considerations about our manuscript, "Health Services, Socioeconomic Indicators and Primary Care Coverage in The Mortality by Lower Genital Tract and Breast Neoplasias in Brazilian Women During the Reproductive and Non-Reproductive Periods" (Manuscript ID: ijerph-860766), submitted to International Journal of Environmental Research and Public Health (IJERPH).

This response letter contains a point-by-point reply to the peer reviewer’s comments, outlining the changes we have made.

Reviewer #2

The paper in question turns out to be interesting in that it worries the incidence of breast cancer and genital tumors in the Brazilian territory, but at the same time, not from new information that can be used by the research. I suggest that the authors give a different and more original approach to the work.

Answer: Thanks for the comment.

The following paragraph was included in the Introduction section:

“This also occurs in areas with low socioeconomic and educational levels [9,10], showing disparities between Brazilian regions. It is also known that the risk factors for breast and lower genital tract cancer are different in the reproductive and non-reproductive periods. However, prevention and screening strategies in primary care are the same for both periods of life, according to our public policies and reforms [11].”

This paragraph is in L48-52

Author Response File: Author Response.pdf

Reviewer 3 Report

The manuscript analysed the relationship between socioeconomic, health care indicators and primary care coverage in mortality from neoplasms of lower genital tract and breast in Brazilian women during reproductive and non-reproductive periods.  

Authors conducted an ecological study using secondary data on women according to reproductive periods and mortality data from Mortality Information System based on ICD-10, regarding breast and lower genital tract neoplasms in 2017. The manuscript is based on secondary data, and several data sources were used.

The findings of the study show that mortality from breast and female lower genital tract neoplasms in Brazil are not associated with primary care coverage nor health service indicators both in reproductive and non-reproductive periods. It further shows that sociodemographic indicators are associated with mortality from breast cancer and female lower genital tract; income is associated with mortality in the reproductive period and educational level in the non-reproductive period. Findings of the study added new knowledge in the area of breast cancer and lower genital tract cancers. The study is important as it included both reproductive and non-reproductive periods and studied two major cancers occurs in women. It also included social and demographic determinants of health and examined the regional disparities in women’s health in Brazil.

However, there are several shortcomings in the study, and they are listed below:

• The method section discussed data analysis and statistical tests undertaken. However, it is not clear how different sources of data were manipulated and synthesised
• In the statistical analysis, line 102, both qualitative and quantitative variables were mentioned, but it is not clear which items were included in qualitative and quantitative variables. Qualitative variables described as absolute and relative frequencies, but it is not clear which variables were included. Quantitative variables were described as measures of central tendency according to adherence to Gaussian distribution. It is not clear which items were included in the qualitative and quantitative variables.  
• The results show regional differences in the mortality rates, for example, it is reported that highest rates were occurred in the northern region, both for the female population in general (37.59) and for women in the reproductive period (13.95) when compared to the other regions. It is essential to describe each region, socioeconomic status of the region, without the description of the region, it isn't easy to make sense of the results.
• It is important to discuss the limitations with the data manipulation and synthesis of the analysis when using secondary sources of the data.
• The citation in the text should be consistent. It is used as a superscript at the later part of the manuscript which has not done accordingly in pages 1-3. Be consistent with the citation in the text.

The above shortcomings should be addressed before it can be considered for publication.

Author Response

Dear Editor,

We are grateful for the considerations about our manuscript, "Health Services, Socioeconomic Indicators and Primary Care Coverage in The Mortality by Lower Genital Tract and Breast Neoplasias in Brazilian Women During the Reproductive and Non-Reproductive Periods" (Manuscript ID: ijerph-860766), submitted to International Journal of Environmental Research and Public Health (IJERPH).

This response letter contains a point-by-point reply to the peer reviewer’s comments, outlining the changes we have made.

Reviewer #3

The manuscript analysed the relationship between socioeconomic, health care indicators and primary care coverage in mortality from neoplasms of lower genital tract and breast in Brazilian women during reproductive and non-reproductive periods. 

Authors conducted an ecological study using secondary data on women according to reproductive periods and mortality data from Mortality Information System based on ICD-10, regarding breast and lower genital tract neoplasms in 2017. The manuscript is based on secondary data, and several data sources were used.

The findings of the study show that mortality from breast and female lower genital tract neoplasms in Brazil are not associated with primary care coverage nor health service indicators both in reproductive and non-reproductive periods. It further shows that sociodemographic indicators are associated with mortality from breast cancer and female lower genital tract; income is associated with mortality in the reproductive period and educational level in the non-reproductive period. Findings of the study added new knowledge in the area of breast cancer and lower genital tract cancers. The study is important as it included both reproductive and non-reproductive periods and studied two major cancers occurs in women. It also included social and demographic determinants of health and examined the regional disparities in women’s health in Brazil.

However, there are several shortcomings in the study, and they are listed below:

Comment 1: The method section discussed data analysis and statistical tests undertaken. However, it is not clear how different sources of data were manipulated and synthesized.

Answer: Thanks for the comment, we modified the following paragraphs in the method section:

“Data Source and collection procedure

We analyzed the 26 Brazilian federative units divided in 5 regions (North, Northeast, Southeast, South and Midwest) with distinct climatic and socioeconomic characteristics. The population data are from the Brazilian Institute of Geography and Statistics (IBGE-www.ibge.gov) [12].

Mortality data were extracted from the Mortality Information System (acronym in Portuguese: SIM), included in the Informatics Department of the Unified Health System (acronym in Portuguese: DATASUS, www.datasus.gov.br). Deaths due to lower genital tract and breast cancer are registered according to the international classification of disease - tenth edition (ICD-10), namely: Malignant neoplasm of breast - C50; Malignant neoplasm of vulva - C51; Malignant neoplasm of vagina - C52; Malignant neoplasm of cervix uteri - C53; Malignant neoplasm of corpus uteri - C54; Malignant neoplasm of uterus, part unspecified - C55; Malignant neoplasm of ovary - C56; Malignant neoplasm of other and unspecified female genital organs - C57 [13].

The data referring to the Primary Care Coverage were extracted from the Primary Care Information System (acronym in Portuguese: SIAB), also included in DATASUS (www.datasus.gov.br ) [14].

The health indicators (Number of beds, physicians, nurses and Mammography devices per 100,000 inhabitants) were extracted from the National Register of Health Establishments (acronym in Portuguese: CNES), also included in DATASUS (www.datasus.gov.br ) [15].

Finally, the socioeconomic indicators (GINI index, Female illiteracy rate per 100,000 inhabitants, Per Capita Income and Population´s average years of study) were extracted from the National Household Sample Survey (acronym in Portuguese: PNAD), from the Brazilian Institute of Geography and Statistics (IBGE-www.ibge.gov)The GINI index is a coefficient that measures inequality in terms of income distribution in each group, numerically varies from zero to one (the higher its value, the higher the inequality). Per capita income is an indicator that is obtained by dividing national income by the number of inhabitants in the place (the currency exchange rate is variable; in December 2017, one US dollar was equivalent to 3.31 Brazilian Reals) [16].”

These paragraphs are in L62-91

Comment 2: In the statistical analysis, line 102, both qualitative and quantitative variables were mentioned, but it is not clear which items were included in qualitative and quantitative variables. Qualitative variables described as absolute and relative frequencies, but it is not clear which variables were included. Quantitative variables were described as measures of central tendency according to adherence to Gaussian distribution. It is not clear which items were included in the qualitative and quantitative variables.  

Answer: Thanks for the comment, in this study all variables were quantitative. We apologize for the mistake and modified the following paragraph in the method section:

“Quantitative variables were described as measures of central tendency according to adherence to Gaussian distribution. Crude mortality rates were calculated by the ratio between the number of deaths reported by cancer in lower genital tract and breast in 2017 for every 100,000 women according to age groups.”

This paragraph is in L119-122

Comment 3: The results show regional differences in the mortality rates, for example, it is reported that highest rates were occurred in the northern region, both for the female population in general (37.59) and for women in the reproductive period (13.95) when compared to the other regions. It is essential to describe each region, socioeconomic status of the region, without the description of the region, it isn't easy to make sense of the results.

Answer: Thanks for the comment, we added the following paragraph and the table (that were in Supplementary Material) in the results section (in this way the Supplementary Material was excluded):

“Regarding the characteristics of the health and socioeconomic services of Brazilian regions and states, it was observed that the largest number of physicians per 100,000 inhabitants is found in the south and southeast regions, with an average of 1.6 for both; nurses, in the south (105.3) and the largest number of beds in the northeast and south (1.7).As for the rate of mammography devices, the southern region concentrates the largest portion with an average of 1.6, as well as the lowest Gini index (0.47). The illiteracy rate was higher in the Northeast (17.9) and the average year of study in the Southeast (8.7). The average per capita income was higher in the central-west region (490.42) (table 2).

Table 2 - Characteristics of the health and socioeconomic service of Brazilian federative units in 2017.

* Per 100,000 inhabitants; 1 U$ quoted at R $ 3.31 in December 2017”

This paragraph and table are in L156-166

And we also modified the following paragraphs in the discussion section:

“Our results show that in the reproductive period, the increase in mortality was associated with a lower income for women. In order to understand the results associated with socioeconomic and health indicators, it is necessary to analyze the economic and health particularities that exist in each Brazilian region.

Socioeconomic indicators such as gini index, per capita income, literacy level and average years of schooling showed better results in the south and southeast regions, while the north and northeast regions show more discouraging indicators. The south and southeast regions in particular have a peculiar characteristic, which is the great existing urban development and the concentration of industry in these places, which allows the improvement of these results. The midwest region, on the other hand, presents average results, which may be associated with its urban and rural profile, concentrating the Brazilian capital Distrito Federal and large states such as Goiás [34].

The health indicators follow the same pattern as the previous ones, except for the variables number of nurses and beds in the Brazilian healthcare system, which presented approximate values ​​between regions. The presence of physicians and mammography rate are variables that showed lower values ​​in the north and northeast regions, and as consequence, higher mortality rates in these regions. For example, breast cancer, since the difficulty in accessing the mammography exam causes a delay in diagnosis, which reduces the chances of treatment and survival [35-37].”

These paragraphs are in L277-293

Comment 4: It is important to discuss the limitations with the data manipulation and synthesis of the analysis when using secondary sources of the data.

Answer: Thanks for the comment, we modified the following paragraphs in the discussion section:

“A limitation of the study is the possible fragility in the use of secondary sources from DATASUS and IBGE databases. However, the improvement in the completeness of epidemiological variables in cancer-related deaths throughout recent years must be considered, which renders this system to be an important national tool for access to mortality data and development of ecological studies [51].”

This paragraph is in L339-342

Comment 5: The citation in the text should be consistent. It is used as a superscript at the later part of the manuscript which has not done accordingly in pages 1-3. Be consistent with the citation in the text.

Answer: Thanks for the comment, to improve the consistence of the citations we added the following references:

11. Mullachery P, Macinko J, Silver D. Have Health Reforms in Brazil Reduced Inequities in Access to Cancer Screenings for Women?. J Ambul Care Manage. 2020;43(3):257-266. doi:10.1097/JAC.0000000000000333
12. Instituto Brasileiro de Geografia e Estatística. IBGE atualiza dados geográficos de estados e municípios brasileiros. Ed. Geociências. Brasil, 2020. Disponível em <https://agenciadenoticias.ibge.gov.br/agencia-sala-de-imprensa/2013-agencia-de-noticias/releases/27737-ibge-atualiza-dados-geograficos-de-estados-e-municipios-brasileiros
13. Departamento de Informática do SUS. Sistema de Informação Sobre Mortalidade. 2020. Disponível em <http://www2.datasus.gov.br/DATASUS/index.php?area=0205&id=6937>
14. Departamento de Informática do SUS. Sistema de Informação da Atenção Básica. 2020. Disponível em <https://aps.saude.gov.br/ape/esus>
15. Departamento de Informática do SUS. Cadastro Nacional de Estabelecimentos de Saúde. 2020. Disponível em <http://cnes.datasus.gov.br/>
16. Instituto Brasileiro de Geografia e Estatística. Pesquisa Nacional por Amostra de Domicílios, PNAD. 2020. Disponível em < https://www.ibge.gov.br/estatisticas/sociais/populacao/9127-pesquisa-nacional-por-amostra-de-domicilios.html?=&t=o-que-e>
17. COUGHLIN, S. S. Social determinants of breast cancer risk, stage, and survival. Breast Cancer Research and Treatment, p. 1-12, 2019.
18. Technical report. Disponível em: http://www.ipeadata.gov.br/
19. CUNHA, G. N. DA et al. Rastreamento do câncer de mama: modelo de melhoria do acesso pelo uso de mamógrafos móveis. Revista Panamericana de Salud Pública, v. 43, p. 1, 19 jun. 2018.
20. MIOWSKI, A. et al. Diretrizes para detecção precoce do câncer de mama no Brasil. II - Novas recomendações nacionais, principais evidências e controvérsias. Cadernos de Saúde Pública, v. 34, n. 6, 21 jun. 2018.
21. MOLINA, L.; DALBEN, I.; DE LUCA, L. A. Análise das oportunidades de diagnóstico precoce para as neoplasias malignas de mama. Revista da Associação Médica Brasileira, v. 49, n. 2, p. 185–190, jun. 2003.
22. DE OLIVEIRA, N. P. D. et al. Association of cervical and breast cancer mortality with socioeconomic indicators and availability of health services. Cancer Epidemiology, v. 64, p. 101660, 2020.

43. DUNN, B. K. et al. Health disparities in breast cancer: biology meets socioeconomic status. Breast cancer research and treatment, v. 121, n. 2, p. 281-292, 2010.
44. ANDAYA, A. A. et al. Socioeconomic disparities and breast cancer hormone receptor status. Cancer Causes & Control, v. 23, n. 6, p. 951-958, 2012.
45. ROCHA-BRISCHILIARI, S. C. et al. The rise in mortality from breast cancer in young women: trend analysis in Brazil. PLoS One, v. 12, n. 1, p. e0168950, 2017.
46. Programa Nacional de Imunizações. Boletim Informativo Vacinação contra HPV. Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Vigilância das Doenças Transmissíveis. Brasília, DF, 2016.
47. GAO, Y. et al. Association of menstrual and reproductive factors with breast cancer risk: results from the Shanghai Breast Cancer Study. International journal of cancer, v. 87, n. 2, p. 295-300, 2000.
48. GRAVENA, A. A. et al. Outcomes in late-age pregnancies. Revista da Escola de Enfermagem da USP, v. 46, n. 1, p. 15, 2012.
49. AZEVEDO E SILVA, G. et al. Access to early breast cancer diagnosis in the Brazilian Unified National Health System: an analysis of data from the Health Information System. Cadernos de saude publica, v. 30, n. 7, p. 1537-1550, 2014.
50. BARBOSA, I. R. et al. Desigualdades regionais na mortalidade por câncer de colo de útero no Brasil: tendências e projeções até o ano 2030. Ciência & Saúde Coletiva, v. 21, p. 253-262, 2016.
51. FELIX, J. D. et al. Avaliação da completude das variáveis epidemiológicas do Sistema de Informação sobre Mortalidade em mulheres com óbitos por câncer de mama na Região Sudeste: Brasil (1998 a 2007). Ciência & Saúde Coletiva, v. 17, p. 945-953, 2012.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

This reviewer accepts the responses. 

Author Response

Dear Reviewer 1 

I am glad that The Reviewer accepts the responses. 

Best regards 

Isabel. 

Reviewer 2 Report

Author Response

Dear Editor,

We are grateful for the considerations about our manuscript, " Health Services, Socioeconomic Indicators and Primary Care Coverage in Mortality by Lower Genital Tract and Breast Neoplasias in Brazilian Women During Reproductive and Non-Reproductive Periods" (Manuscript ID: ijerph-860766), submitted to International Journal of Environmental Research and Public Health (IJERPH).

We made undergone English language editing by MDPI (ID: 21015). The text has been checked for correct use of grammar and common technical terms, and edited to a level suitable for reporting research in a scholarly journal.

Reviewer #2

• English language and style are fine/minor spell check required.

Thank you for comments.

We made undergone English language editing by MDPI (ID : 21015). The text has been checked for correct use of grammar and common technical terms, and edited to a level suitable for reporting research in a scholarly journal.

• Does the introduction provide sufficient background and include all relevant references? (x) can be improved.

Thank you for comments.

We made comments at the Background and included two references:

“ ROCHA, T. A. H. et al. Primary Health Care and Cervical Cancer Mortality Rates in Brazil. Journal of Ambulatory Care Management, v. 40, p. S24–S34, 2017.”

“ Mullachery P, Macinko J, Silver D. Have Health Reforms in Brazil Reduced Inequities in Access to Cancer Screenings for Women?. J Ambul Care Manage. 2020;43(3):257-266. doi:10.1097/JAC.0000000000000333”.

• Is the research design appropriate?

Thank you for comments.

We included limitation of the study at discussion section.

“ A limitation of the study is the possible fragility of the use of secondary sources from the DATASUS and IBGE databases. However, the improvement in the completeness of epidemiological variables in cancer-related deaths over recent years must be considered, making this system an important national tool for access to mortality data and the development of ecological studies”.

• Are the results clearly presented? (x) must be improved

Thank you for comments.

We did readjust according to the results shown in the tables and figures.

• Are the conclusions supported by the results? (x) must be improved

Thank you for comments.

Conclusions:

“ Mortality from breast and female lower genital tract neoplasms in Brazil are not associated with primary care coverage nor health service indicators, both in reproductive and non-reproductive periods.

Sociodemographic indicators are associated with mortality from breast and female lower genital tract cancer, with income being associated with mortality in the reproductive period and educational level in the non-reproductive period.

Health care policies for women and actions to prevent breast and lower genital tract cancer in primary health care should include intersectoral strategies which consider improvements in health determinants such as education and socioeconomic level, as well as the specifics of each period of life.”

Best regards

Isabel.

Author Response File: Author Response.pdf