Survival and predictors of breast cancer mortality in South Ethiopia: A retrospective cohort study

Abel Shita; Alemayehu Worku Yalew; Edom Seife; Tsion Afework; Aragaw Tesfaw; Zenawi Hagos Gufue; Friedemann Rabe; Lesley Taylor; Eva Johanna Kantelhardt; Sefonias Getachew

doi:10.1371/journal.pone.0282746

Peer Review History

Original SubmissionAugust 1, 2022
7 Sep 2022 Decision Letter - Mohammad-Reza Malekpour, Editor PONE-D-22-21553 Survival and Predictors of Breast Cancer Mortality in South Ethiopia: A Retrospective Cohort StudyPLOS ONE Dear Dr. Getachew, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Considering the setting of the study (low income country), it provides a valuable insight into predictors of survival and predictors of mortality in breast cancer patients in Ethiopia; however, there are some major points that need to be revised before publication. One of the main limitation of the study is relatively small sample size for a country with more than 100 millions population. 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The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Overall assessment: Shita et al. reported the survival and predictors of mortality among breast cancer patients in South Ethiopia in a retrospective cohort study. Although some studies with a similar topic have been performed in Ethiopia or other countries, I think the study is significant to the field and it can be added to the body of studies with the same subject performed in low resource settings to feed meta-analysis papers. In my opinion, the major strength of the study is the questions that are asked from participants, which were not just focused on histological and TNM staging of the tumor, and included the area of residence, treatment adherence, access to facilities, and so forth. These variables can add to the public health value of the study and reveal barriers that will result in a poor outcomes. As another strength, the results have been presented clearly and organized. However, the manuscript should be revised and improved in discussion to better reflect the results of the study, interpret them and provide solutions. Overall, I think the manuscript needs revision. Comments: • Introduction section The authors mention that only one study about the survival of breast cancer patients exists in Ethiopia. What about the article published by Tiruneh et al. in 2021? • Introduction section, The last paragraph Please restate the objective of the study in this paragraph as a scientific-writing norm in literature. • Result section, Sampling and data collection procedures 337 patients are too low for a country with a 114 million population. Please mention the population in the south of Ethiopia which is covered by this study. Besides, in the case of available literature, this could be a discussion material that how many patients do not go to hospitals for cancer treatment and are not registered anywhere. As it seems, the cases studied here are only the tip of the iceberg, and the patient’s real crude number is much higher. If available, also present data on the completeness of cancer registries in Ethiopia. • Discussion, second paragraph The result cannot be due to the availability of treatments because such treatments are more available in Iran. It could be postulated that the authors should consider the worst scenario as the right one. Please expand your discussion on this issue: according to the literature, which of the two scenarios seems more rational? Besides, you should also add the reference of Tiruneh et al. which is lacking on the reference list. • Discussion Section The discussion is not engaging. It focuses on comparing the study results with other studies worldwide; however, lacks providing solutions for the mentioned problems in low-resource settings or examples of countries with successful control of the disease burden. Most of the discussion is regarding how the diagnosis of patients in advanced stages is affecting disease prognosis. The idea is discussed in several separate paragraphs, whereas it can be presented in one organized paragraph, ending with available solutions for disease screening or increasing awareness of the disease, which should be compatible with the countries’ HDI and GDP context. Please also focus and expand your discussion on KAP studies and studies on barriers and facilitators of following breast cancer treatment in accordance with your study. • Please increase the quality of graphs/figures. Reviewer #2: This paper reported the survival and predictors of mortality among breast cancer patients in South Ethiopia on 302 breast cancer patients diagnosed from 2013 to 2018. As a developing country in Africa, Ethiopia needs more consideration from health authorities to decrease the burden of diseases. Cancer diagnosis and management are costly procedures that need proper infrastructure and specialized personnel. Therefore, broadly available infrastructures may be lacking in countries such as Ethiopia, and considering related studies to investigate the ongoing diseases is critical. Consequently, I think more studies in this setting should be conducted. The current manuscript needs further revisions to make it sound scientifically acceptable. My comments are as follows: Evidence and examples: Major issues: • As this study is a retrospective, findings may be affected by the study setting. Especially for finding the predicting factors. • The authors mentioned all data are fully available without restriction. Therefore, please upload the data for this submission or provide any alternate options for receiving the data. • The discussion storyline is unorganized, and readers cannot find a path in the narration of the discussion section. Also, some short paragraphs could be merged with other related sentences. • The introduction consisted of some information that is not related to the aim and results of this study. • For the sentence “The median survival was 50.61 months (IQR=18.38-50.80)”, the median is near the upper quartile. I suggest rechecking the results and providing the data supporting this statement. • Ethical statement: Please include the approval number of this research if it is available. • The draft had some grammatical, English fluency, and readability issues. Please address these issues with the assistance of an English expert. • Please mention this research only studied female breast cancer in the abstract section. Minor issues: • Abbreviations were not defined in the abstract: WHO, IQR, AHR, CI. • Reporting the numbers with one decimal is suggested. • As this study is a descriptive study, it is recommended to add the study period to the aim of the study. ****** 6. 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Revision 1
24 Jan 2023 Author Response Response to reviewers Reviewer's Point by Point Responses to the Questions 1. Introduction section The authors mention that only one study about the survival of breast cancer patients exists in Ethiopia. What about the article published by Tiruneh et al. in 2021? Response: We greatly appreciate the reviewer’s positive comments. We have carefully revised the studies conducted in Ethiopia regarding the survival of breast cancer patients and we obtained another recent study, accordingly, we have added the article published by Tiruneh et al. in 2021 in the introduction section (See page 6; line number 141-142). 2. Introduction section, the last paragraph: Please restate the objective of the study in this paragraph as a scientific-writing norm in literature. Response: We greatly appreciate the reviewer’s positive comments. We have carefully revised the last paragraph section of the introduction of the manuscript and accordingly, we have restated the objective of the study in this paragraph (See page 4; line number 152-153). 3. Result section, sampling and data collection procedures 337 patients are too low for a country with a 114 million population. Please mention the population in the south of Ethiopia which is covered by this study. Besides, in the case of available literature, this could be a discussion material that how many patients do not go to hospitals for cancer treatment and are not registered anywhere. As it seems, the cases studied here are only the tip of the iceberg, and the patient’s real crude number is much higher. If available, also present data on the completeness of cancer registries in Ethiopia. Response: We greatly appreciate the reviewer’s positive comments. We have carefully revised the sampling and data collection procedures of the study. Since we have no recent census data, what we have included in the study setting is the total population of the Southern region of Ethiopia, from the 2007 national census. We have not got published data that describes the completeness of the cancer registries in Ethiopia. (See page 6; line number 160- and Page 7, line number 161). We have also mentioned in the limitation part of the study. 4. Discussion, second paragraph The result cannot be due to the availability of treatments because such treatments are more available in Iran. It could be postulated that the authors should consider the worst scenario as the right one. Please expand your discussion on this issue: according to the literature, which of the two scenarios seems more rational? Besides, you should also add the reference of Tiruneh et al. which is lacking on the reference list. Response: We greatly appreciate the reviewer’s positive comments. A sentence indicating the availability of treatment as a reason for the discrepancy is now omitted. Tiruneh et al. (2021) is now added to the discussion. The discussion is extended suggesting the difference with between the studies could be due to a higher number of losses to follow-up in our study (18%), and this which in turn affected the actual overall survival. Another reason could be the availability of systemic therapy, as patients have access to it, unlike the western Ethiopia study that reported survival without it and Hawassa is active since couple of years ago as preparing to offer radiotherapy 5. Discussion Section The discussion is not engaging. It focuses on comparing the study results with other studies worldwide; however, lacks providing solutions for the mentioned problems in low-resource settings or examples of countries with successful control of the disease burden. Most of the discussion is regarding how the diagnosis of patients in advanced stages is affecting disease prognosis. The idea is discussed in several separate paragraphs, whereas it can be presented in one organized paragraph, ending with available solutions for disease screening or increasing awareness of the disease, which should be compatible with the countries’ HDI and GDP context. Please also focus and expand your discussion on KAP studies and studies on barriers and facilitators of following breast cancer treatment under your study. Response: thanks for your critical look and positive comments. We have significantly improved in each section to make more engaging as we addressing our messages. In most part we improved the section and addressed our summarizing message at the end of the discussions and significantly revised it. 6. Please increase the quality of graphs/figures. Response: We greatly appreciate the reviewer’s positive comments. We have increased the quality of the available figures (See each figure). Reviewer number 2 This paper reported the survival and predictors of mortality among breast cancer patients in South Ethiopia on 302 breast cancer patients diagnosed from 2013 to 2018. As a developing country in Africa, Ethiopia needs more consideration from health authorities to decrease the burden of diseases. Cancer diagnosis and management are costly procedures that need proper infrastructure and specialized personnel. Therefore, broadly available infrastructures may be lacking in countries such as Ethiopia, and considering related studies to investigate the ongoing diseases is critical. Consequently, I think more studies in this setting should be conducted. The current manuscript needs further revisions to make it sound scientifically acceptable. My comments are as follows: Evidence and examples Major issues 1. As this study is a retrospective, findings may be affected by the study setting. Especially for finding the predicting factors. Response: We greatly appreciate the reviewer’s positive suggestion. Since it is the nature of retrospective studies, we may get missing data which can influence the generalizability of the study. Despite we have included the raised concern in our discussion part; an appropriate design of these studies can provide relevant data for policymakers and the wider scientific community. 2. The authors mentioned all data are fully available without restriction. Therefore, please upload the data for this submission or provide any alternate options for receiving the data. Response: We greatly appreciate the reviewer’s positive suggestion. We have mentioned in the second section as stated “The data underlying the results presented in the study will be available from the main or corresponding author in reasonable request” from the options listed. The discussion storyline is unorganized, and readers cannot find a path in the narration of the discussion section. Also, some short paragraphs could be merged with other related sentences. Response: We greatly appreciate the reviewer’s positive comments. We have carefully revised the entire discussion section of the manuscript; by making the flow of ideas as organized, simple, scientifically sound, and as short as possible (See each paragraph of the discussion section). 3. The introduction consisted of some information that is not related to the aim and results of this study. Response: We greatly appreciate the reviewer’s positive comments. We have carefully revised each piece of information written under the introduction section of the manuscript and we have amended it accordingly (See each paragraph of the introduction section). 4. For the sentence “The median survival was 50.61 months (IQR=18.38-50.80)”, the median is near the upper quartile. I suggest rechecking the results and providing the data supporting this statement. Response: We greatly appreciate the reviewer’s positive comments. We have carefully checked the findings by doing the data analysis again and we found that the 25th percentile was not-estimable as rightly seen in the Kaplan Meir curve. Accordingly, we have modified the median survival time (See Page 13; line number 295-296). 5. Ethical statement: Please include the approval number of this research if it is available. Response: We greatly appreciate the reviewer’s positive comments. We have added the ethical approval number obtained from the research and ethical committee of the Scholl of Public Health, Addis Ababa University (See page 21; line number 450-451). 6. The draft had some grammatical, English fluency, and readability issues. Please address these issues with the assistance of an English expert. Response: We greatly appreciate the reviewer’s positive suggestion. We have consulted English language experts and now we have amended the possible grammatical, and readability issues raised by the experts. 7. Please mention this research only studied female breast cancer in the abstract section. Response: We greatly appreciate the reviewer’s positive suggestion. We have specified the study population as female breast cancer patients in the abstract section of the manuscript (See page 2; line number 59). Minor issues 1. Abbreviations were not defined in the abstract: WHO, IQR, AHR, CI. Response: We greatly appreciate the reviewer’s positive suggestion. We have defined each possible abbreviation listed in the abstract, but the confidence interval “CI” should not be listed as it is a common statistical abbreviation (See page 2; line number 52). 2. Reporting the numbers with one decimal is suggested. Response: We greatly appreciate the reviewer’s positive suggestion. Even though there is no clear recommendation from the journal regarding decimal point use, we have amended the decimal points write-up accordingly except for the P-value and crude and adjusted hazard ratio results (See each decimal described). 3. As this study is descriptive, it is recommended to add the study period to the aim of the study. Response: We greatly appreciate the reviewer’s positive suggestion. We have added the study period, which is the data extraction period, to the aim method section of the manuscript (See page 7; line number 166-167). Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0282746.r002
22 Feb 2023 Decision Letter - Mohammad-Reza Malekpour, Editor Survival and Predictors of Breast Cancer Mortality in South Ethiopia: A Retrospective Cohort Study PONE-D-22-21553R1 Dear Dr. Getachew, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Mohammad-Reza Malekpour Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: I appreciate authors for the revisions on the manuscript. I think most of my comments have been addressed andthe manuscript is now in better shape. Reviewer #2: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0282746.r003
Formally Accepted
24 Feb 2023 Acceptance Letter - Mohammad-Reza Malekpour, Editor PONE-D-22-21553R1 Survival and Predictors of Breast Cancer Mortality in South Ethiopia: A Retrospective Cohort Study Dear Dr. Getachew: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Mohammad-Reza Malekpour Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0282746.r004

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