Delayed presentation of breast cancer patients and contributing factors in East Africa: Systematic review and meta-analysis

Chalie Mulugeta; Tadele Emagneneh; Getinet Kumie; Betelhem Ejigu; Abebaw Alamrew

doi:10.1371/journal.pone.0309792

. 2024 Nov 11;19(11):e0309792. doi: 10.1371/journal.pone.0309792

Delayed presentation of breast cancer patients and contributing factors in East Africa: Systematic review and meta-analysis

Chalie Mulugeta ^1,^*, Tadele Emagneneh ¹, Getinet Kumie ², Betelhem Ejigu ¹, Abebaw Alamrew ¹

Editor: Wenjie Shi³

PMCID: PMC11554124 PMID: 39527621

Abstract

Introduction

Breast cancer remains a significant public health issue, with delayed medical attention often leading to advanced stages and poorer survival rates. In East Africa, evidence on the prevalence and factors contributing to the delayed presentation of breast cancer is limited. As a result, this study aims to assess the pooled prevalence of delayed breast cancer presentation and identify contributing factors in East Africa.

Methods

We conducted a systematic review of observational studies from East Africa using PubMed, Google Scholar, Embase, Cochrane Library, Hinari, and Mednar databases. The Newcastle Ottawa 2016 Critical Appraisal Checklist assessed methodological quality. Publication bias was evaluated using a funnel plot and Egger’s test, and heterogeneity was examined with the I-squared test. Data were extracted with Microsoft Excel and analyzed using Stata 11.

Results

The pooled prevalence of delayed presentation among breast cancer patients in East Africa was 61.85% (95% Confidence Interval: 48.83%–74.88%). Significant factors contributing to delayed presentation included visiting traditional healers (Adjusted Odds Ratio: 3.52; 95% CI: 1.43–5.59), low educational levels (Adjusted Odds Ratio: 3.61; 95% CI: 2.39–4.82), age>40 years (Adjusted Odds Ratio 1.87; 1.03, 2.71), absence of breast pain (Adjusted Odds Ratio 2.42; 1.09, 3.74), distance >5km away from home to health institution (Adjusted Odds Ratio 2.89; 1.54, 4.24), and rural residence (Adjusted Odds Ratio: 3.33; 95% CI: 2.16–4.49).

Conclusion

This meta-analysis’s findings demonstrated that over half of breast cancer patients in East Africa delayed detection. Significant factors associated with delayed presentation include age over 40 years, illiteracy, rural residence, use of traditional healers, distance greater than 5 km from a health facility, and absence of breast pain. Healthcare stakeholders and policymakers must be focused on raising awareness and educating people to encourage early detection and prompt therapy.

Introduction

Globally, 2.3 million women received a breast cancer diagnosis in 2022, and 670,000 people died from the disease [1]. While breast cancer mortality is highest in less developed nations, the disease’s incidence is higher in more developed nation [2]. Sub-Saharan Africa as a whole is facing a growing cancer-related public health burden. Currently, 4% of Ethiopian mortalities are related to cancer [3]. In Africa, women die from breast cancer at a rate of 20% and account for 28% of all cancer cases. Incidence rates are still generally varied in Africa, estimated below 35 per 100,000 women in most countries [4], Kenya 52 [5], Zimbabwe 33 [6] and Uganda 34 [7] per 100, 000 women were breast cancer incidence.

Today, the World Health Organization announced the Global Breast Cancer Initiative, a significant new cooperative effort aimed at preventing an estimated 2.5 million deaths worldwide from breast cancer by 2.5% year until 2040 [8]. To achieve these goals, WHO launched early detection (60 percent of cases detected in the early stages), prompt diagnosis (60 days), and thorough care (80% of cases completed with treatment) [9].A systematic review and meta-analysis revealed that the average duration between recognizing symptoms and presenting them to a medical professional was less than 4 months in North Africa and between 3 and 6 months in sub-Saharan Africa [10]. Similar research conducted in Africa showed that the eastern and central areas had the worst rates of late presentation (>90 days), with an overall estimate of 54% [11]. A systematic review and meta-analysis done on breast cancer patients report that delays of three to six months are linked to a decreased chance of survival [12].

Evidence showed that the effects of delay on prognosis have generally demonstrated that longer delays are linked to malignancies that are diagnosed at an advanced stage, which lowers the likelihood of survival [12–14]. Longer patient delays were linked to bigger tumor sizes, positive nodes, and a 24% death rate compared to shorter patient delays [15]. Longer delays were associated with lower survival rates for women, both from the date of diagnosis and from the beginning of symptoms [16]. Research done on the types and timing of symptoms experienced by breast cancer patients, the disease does not present with a lump at first present with symptoms later, and are more likely to have their doctor delayed sending them for a second opinion [17]. Previous Systematic Review and meta-analysis revealed that low education level [10, 18–21], low-income status [10, 18, 21], Symptom misinterpretation [11, 22], preference for alternative care [11, 21–23], older age [19, 21], no family history of breast cancer [19], not performing breast self -examination [20, 23], not married [21], poor knowledge about cancer [21, 23], socio-cultural factors such as belief [22, 23] and lack of trust in access health care [22] were the contributing factors of late patient presentation of breast cancer.

According to a comprehensive analysis conducted on Asians, breast exams and symptoms have consistently demonstrated a major impact on minimizing the amount of time that a diagnosis is delayed [24].A systematic review done on barriers of late presentation and late-stage diagnosis of breast cancer revealed that poor awareness of symptoms and risk factors, anxiety about finding breast abnormalities, fear of cancer treatments, worry of partner desertion, shame about revealing symptoms to medical experts, taboo and stigmatism were some of the variables that contributed to patient delays [25].Previous primary studies were done in the world the coverage of late patient presentation of breast cancer ranges from25% [26]- 89% [27] and positively associated with by range of factors such as individual level (socio-demographic [17, 28, 29], cultural belief [30–32], husband’s attitude and support [27, 32], family income [33]), health service level (distance, accessibility, and availability) [29, 30, 34] and knowledge level [27, 31, 34], absence of pain in the breast [35], no family history of breast CA [29] and not practice self-breast examination [29].

There was previous primary research conducted in East Africa to determine the prevalence of delayed presentation of breast cancer patients and associated factors; however, findings from those studies varied across countries. To the best of our knowledge, this topic has not yet been investigated by systematic review and meta-analysis at the regional level. In particular, this study covered a wider geographical area and provided pooled results. This information is necessary for policy planners and program managers to identify gaps in the delayed presentation of breast cancer patients and to plan strategies to reduce the delay of breast cancer patients. The development of successful programs that increase medical seeking consultation enhances survival rates and decreases mortality and morbidity of breast cancer patients in the East Africa Region depends on the identification of a single number of common factors. Early identification and prompt treatment of breast cancer are crucial for improving maternal health. Systematic reviews and meta-analyses are necessary to address this issue. Thus, the goal of this study was to assess the pooled prevalence of delayed presentation of breast cancer patients and contributing factors in East Africa.

Methods and materials

Study protocol and reporting

This systematic review and meta-analysis was carried out per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria [36] (S1 File). The eligibility criteria were adapted from the Newcastle Ottawa 2016 review guidelines [37].We used Endnote (version X7) reference management software to download, organize, and review and Zotero to cite related articles.

Inclusion criteria

Study area: Only research carried out in East Africa.

Participants in the study: All quantitative studies with indicators or variables indicating late patient presentation of breast cancer.

Study types: Observational cross-sectional studies.

Results of interest: The main investigations revealed the frequency of delayed patient presentation and contributing factors.

Publication condition: We included published articles written in English. There are no restrictions on race and publication date.

Language: Correspondingly, all primary studies published in the English language and reported the prevalence and/or associated factors on Delayed presentation of breast cancer patients in East Africa and fulfill the following criteria were included in this review (Table 1).

Table 1. Show the inclusion and exclusion criteria.

Study characteristics	Inclusion criteria	Exclusion criteria
Design	observational studies Cross-sectional studies	Clinical trials, qualitative studies, editorial letters, case reports/series
Population	Breast cancer patients	Patients with malignancies of other body parts
Condition	Delayed presentation of breast cancer patients	Unclear to determine the time of presentation of breast cancer patient, articles only reviews and descriptive static’s
Context	Studies conducted in East Africa	Studies not from East Africa
Language	English	English

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Exclusion criteria

Excluded from the study were anonymous reports, duplicate research, articles lacking an abstract or full text, and qualitative investigations. We excluded systematic reviews, case reports, and retrospective reviews. We also excluded studies focusing on specific factors and frequency with descriptive studies. Since there was no concrete data to take from this research, they were eliminated. To increase the similarity of the studies included in the meta-analysis with regard to all significant factors, research carried out in particular populations was also eliminated.

Variable measure

Patient delay was defined as time intervals of more than 12 weeks from the first symptom recognition to the first medical consultation [26, 28, 31, 34].

The place of residence was classified as rural or urban and educational status was classified as secondary or above and below secondary, traditional healer was categorized as visit or not visit traditional healer, having no family history of breast cancer was categorized as having a history or not, lump under armpit grouped in to yes or no marital status grouped in to married or not married. Age is grouped into two categories: < 40 or = >40 years. About distance from home to the health facility was grouped into <5km and >5km away. Breast pain is grouped as feeling pain or not. Employee was grouped into employee or not employee.

Search strategy

A systematic search of peer-reviewed, published literature in English was conducted to identify the factors contributing to the late presentation of breast cancer in East Africa (S2 File). We looked through the databases at PubMed, Hinari, EMBASE, Cochrane, CINHAL, Google Scholar, and Mednar to find pertinent research. To find pertinent key phrases, we first searched by article title in PubMed, Google, and Google Scholar. Secondly, we discovered related ideal keywords. Third, we conducted a second search using these phrases in the databases after looking for more research in the reference lists of all the recognized papers and publications. Terms like "breast cancer," "associated factors," "predictors," "determinants," "contributing factors," "prevalence," "magnitude," "proportion," "delayed patient presentation," "late presentation breast cancer," "late diagnosis breast cancer," "late diagnosis of the patient," "East Africa," In addition, eastern African countries, namely, Ethiopia, Ertriea, Sudan, South Sudan, Djibouti, Kenya, Rwanda, Zimbabwe, Tanzania, Uganda, Somalia, Burundi, Namibia, Botswana, Reunion, Mayotte, Seychelles, Madagascar, Marituis and Democratic republic of Congo were also included to ensure a comprehensive search. We experimented and improved utilizing several test searches, combining related search phrases with Boolean operators like OR and combining distinct notions using the Boolean operator AND.

Data extraction

The data was extracted using Microsoft Excel. Two distinct data extraction formats were utilized to collect the information needed for analysis. In the extraction form for prevalence, we included the author’s last name, the year the work was published, the study country, the study design, sample size, the frequency of breast cancer, the prevalence and its confidence interval, and the quality score of each study. The author’s last name and the year of publication were also included in the data extraction format for contributing factors. Every necessary piece of information was separately collected by two writers, who then cross-checked their findings and agreed on any discrepancies.

Quality assessment/critical appraisal

The article was manually transferred to EndNote and checked for duplicates. The inclusion and exclusion criteria were applied to review the remaining articles, focusing on patient delay presentation of breast cancer in East Africa. The Newcastle-Ottawa quality appraisal checklist was used to evaluate the quality of individual studies [37] (S3 File).

Two reviewers evaluated each primary study individually, and a decision was made to accept or reject based on specific criteria. In case of disagreement, the average score of both reviewers was taken. A study was categorized as good quality if it scored more than 50% on quality assessment indicators. Each cross-sectional study was assessed using eight criteria: inclusion criteria, study subject and setting description, valid measurement of exposure, and identification of confounders using objective criteria, confounder handling strategies, outcome measurement, and statistical analysis. Eight cross-sectional studies met quality criteria and were included in the analysis.

Result

A total of 1100 published studies (PubMed = 100, Hinari = 10, Cochrane Review = 85, EMBASE = 10, Google Scholar = 895) were identified. 200 duplicates were removed, leaving 900 abstracts for evaluation. 800 articles were excluded based on criteria methodological issues, not focused on East Africa and not relevant for breast cancer. Resulting in 100 articles was retained for full-text screening. 92 articles were further excluded for various reasons, leaving only 8 studies for final systematic and meta-analysis. Participant overlap was prevented by using the same data source, and studies were evaluated for quality before inclusion (Fig 1).

Study characteristics

Only eight studies were included in this analysis [38–45]. Six articles were included from Ethiopia. Two articles were recruited from Rwanda and Sudan. From the included articles a study population of 2,842 participants, of whom 1095 participants delayed patient presentation of breast cancer. The included articles were published. All the included studies were facility based cross-sectional by design and reported delay presentation of breast cancer patients. The sample sizes across the studies ranged from63 [45] to 441 [42] (Table 2).

Table 2. Description of included articles delayed presentation of breast cancer and associated factors in East Africa.

Id no	Author	Year	Study Design	Country	Actual Sample	Frequency	ES**[95%C]
1	Hassen AM, etal	2021	Cross-sectional	Ethiopia	204	102	50.5(43.6, 57.4)
2	Tesfaw A, etal	2020	Cross-sectional	Ethiopia	371	280	75.7(71.3, 80)
	Shewarega B, etal	2023	Cross-sectional	Ethiopia	269	180	67(62.1, 71.7)
4	Muhammed JA, etal	2022	Cross-sectional	Ethiopia	150	86	57.3(51.3, 63)
5	Gebremariam A, etal.	2019	Cross-sectional	Ethiopia	441	159	36 (33, 38.7)
6	Abiye M, etal.	2023	Cross-sectional	Ethiopia	206	157	76.7(70.8, 82.6)
7	Pace LE, etal	2015	Cross-sectional	Rwanda	144	84	58 (51.9, 64.1)
8	Salih AM, etal	2016	Cross-sectional	Sudan	63	47	74.6 (64.1, 85)

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Pooled prevalence of delayed patient presentation of breast cancer in East Africa

The overall pooled prevalence of delayed patient presentation of breast cancer was 61.85% (95% CI: 48.83–74.88%). Using the random effects model, the pooled effect size of delayed patient presentation of breast cancer showed statistically significant heterogeneity among the included studies (I2-98.1%, p<0001) (Fig 2).

Subgroup analysis

We performed a subgroup analysis by country to address heterogeneity. The subgroup analysis showed that the prevalence of late presentation of breast cancer patients ranged from 50.0% in Rwanda to 74.6% in Sudan. Substantial heterogeneity was estimated, up to 98.6% in Ethiopia (Fig 3).

Publication bias

Publication bias was viewed graphically by funnel plot asymmetry and tested through Egger’s [46]. The p-value was >0.05; there was statistical evidence for the absence of publication bias using the Egger test. Egger’s regression test was not statistically significant, with a P value of 0.089(Fig 4).

Sensitivity analysis

In this meta-analysis, no single study dominated the pooled prevalence of delayed presentation of breast cancer patients in East Africa, according to the results of a random-effects model (Table 3).

Table 3. Shows a sensitivity analysis of delayed presentation of breast cancer patients in east Africa.

Study omitted	Estimate	[95% Conf. Interval]
Anissa Mohammed Hassen, et al	63.47	48.89,	78.04
Aragaw Tesfaw, et al	59.82	46.58,	73.05
Birtukan Shewarega, et al	61.13	46.36,	75.88
Jabir Abdella Muhammed, et al	62.51	47.67,	77.34
Alem Gebremariam, et al	65.60	58.05,	73.17
Mezgebu Abiye, et al	59.71	46.08,	73.35
Lydia E. Pace, et al	62.41	47.64,	77.18
Alaaddin M Salih, et al	60.13	46.23,	74.03
Combined	61.85	48.82,	74.87

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Factors associated with delay presentation of breast cancer patient in East Africa

We included 11 selected variables to identify relationships with the delayed presentation of breast cancer patients in East Africa. Of these, six variables, namely age = >40 years, low educational level, rural residence, visit traditional healer, distance>5km away from the health facility and not feeling breast pain were significantly associated with delayed presentation of breast cancer patients (Table 4). The review also demonstrated that employee; marital status, not having a lump under the armpit, not having awareness of breast cancer and no family history of breast cancer had no statistically significant association with delayed presentation of breast cancer.

Table 4. Factors associated with delayed presentation of breast cancer patients in east Africa.

Variable	Exposed	Comparator	OR (95% CI)	I 2
Visit Traditional medicine healer	Yes	No	3.52; (1.43, 5.59)	99.4%
Age	>40	<40	1.87; (1.03, 2.71)	99%
Educational status	Illiterate	Literate	3.61; (2.39, 4.82)	98.3%
Residence	Rural	Urban	3.33; (2.16, 4.49)	98.6%
Distance from home to health facility	>5km	<5km	2.89; (1.54, 4.24)	97.5%
Breast Pain	Not feeling breast pain	Feeling breast pain	2.42; (1.09, 3.74)	99%

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Age of participant

In the overall analysis of this study age of the participant was significantly associated with delay in presentation of breast cancer patients. Participants with age = >40 years were nearly 2 times more likely to delay presentation than those of age less than 40 years (OR, 1.87; 95% CI: 1.03, 2.71). A random effects model was assumed for the analysis as I2 (99.1%) and Egger test 0.220 with a p-value of (<0.001) showed statistically significant heterogeneity among the included studies for this factor analysis (Fig 5).

Educational status

The overall analysis of studies showed education had a positive impact on delayed breast cancer patients. Participants with low educational status were 3.6 times more likely delay than their counterparts (OR, 3.61; 95% CI: 2.39, 4.82). A random effects model was assumed for the analysis as I2 (98.3%) and Egger test 0.118 with a p-value of (<0.001) showed statistically significant heterogeneity among the included studies for this factor analysis (Fig 6).

Residence

The overall analysis of studies showed that residence had a positive association with delayed presentation of breast cancer patients. Participants with rural residence were 3.3 times more likely to delay than that of their counterparts (OR, 3.33; 95% CI: 2.16, 4.49). A random effects model was assumed for the analysis as I2 (98.6%) and Egger test 0.307 with a p-value of (<0.001) showed statistically significant heterogeneity among the included studies for this factor analysis (Fig 7).

Absence of breast pain

The overall analysis of studies showed not having breast pain had a positive impact on delayed breast cancer patients. Participants who had no breast pain were 2.4 times more likely delay than their counterparts (OR, 2.42; 95% CI: 1.09, 3.74). A random effects model was assumed for the analysis as I2 (99.1%) and Egger test 0.801 with a p-value of (<0.001) showed statistically significant heterogeneity among the included studies for this factor analysis (Fig 8).

Distance from health facility

The overall analysis of studies showed the distance from the health facility had a positive impact on delayed breast cancer patients. Participants who were>5km away from the health facility were nearly 3 times more likely delayed than that their counterparts (OR, 2.89; 95% CI: 1.54,4.24). A random effects model was assumed for the analysis as I2 (97.5%) and Egger test 0.081 with a p-value of (<0.001) showed statistically significant heterogeneity among the included studies for this factor analysis (Fig 9).

Visit traditional healer

The overall analysis of studies showed that visiting traditional healers had a positive impact on delayed breast cancer patients. Participants who have visited traditional healers were 3.52 times more likely delayed than that of their counterparts (OR, 3.52; 95% CI 1.43, 5.59). A random effects model was assumed for the analysis as I2 (99.4%) and Egger test 0.345 with a p-value of (<0.001) showed statistically significant heterogeneity among the included studies for this factor analysis (Fig 10).

Factors not associated with delayed presentation of a breast cancer patient in East Africa

Employee

The meta-analysis showed that employed participants were not significantly associated with delayed presentation. The overall odds ratio was 0.63 with a 95% CI of 0.11–1.15, and a p-value of <0.021. A random effects model was used for the analysis, showing statistically significant heterogeneity among the included studies (I2 = 74.4%, p-value <0.021) as depicted in Fig 11.

Marital status

Marital status was not associated with delayed presentation of breast cancer patients. The overall odd ratio of married women is 1.39(0.90–1.88). Random effect model was used I2,93%) and the Egger test was 0.294 with significant heterogeneity for this analysis (Fig 12).

Not having awareness of breast cancer

The overall analysis of studies showed that not having awareness of breast cancer has no association with delayed presentation of breast cancer patients (OR, 1.58; 95% CI: 0.69, 2.46). A random effects model was assumed for the analysis as I2 (97.2%) and Egger test 0.618 with a p-value of (<0.001) showed statistically significant heterogeneity among the included studies for this factor analysis (Fig 13).

Not having lump under armpit

The overall analysis of studies showed no lump under the armpit had no positive impact on delayed breast cancer patients (OR, 3.34; 95% CI: 0.30, 6.38). A random effects model was assumed for the analysis as I2 (99.7%) and Egger test 0.801 with a p-value of (<0.001) showed statistically significant heterogeneity among the included studies for this factor analysis (Fig 14).

Have no family history of breast cancer

The overall analysis of studies showed no family history of breast cancer had no positive effect on delayed breast cancer patients (OR, 2.693; 95% CI: 0.268,5.118). A random effects model was assumed for the analysis as I2 (99.7%) and Egger test 0.611 with a p-value of (<0.001) showed statistically significant heterogeneity among analyzed factors (Fig 15).

Discussion

The study conducts a detailed analysis of the coverage of delayed patient presentations for breast cancer in Eastern Africa. Breast cancer patients who delayed presenting were shown to have a pooled overall prevalence of 61.85% (95% CI: 48.83–74.88%). This high prevalence of delayed presentation of breast cancer has serious implications for public health in East Africa. There might be increased morbidity and mortality, increased economic burden for treatment and exacerbating poverty, and reduced quality of life due to more severe symptoms. Around the world, between 25% and 89% of breast cancer patients present after their disease has progressed. This disparity might be caused by several factors, including access to the health care facility, quality of health care service, awareness and education level, socioeconomic status, cultural factors, quality of the research, health insurance, financial barriers, the availability of medical supplies, and the article’s publication date.

This study is consistent with previous studies done in different countries in indenesia58% [47],inNigeria72% [48], in Nigeria 68% [49], a systematic review and meta-analysis done in Africa 54% [11], in India50% [50], and in Saudi60.7% [31]. There were a few potential causes, including comparable social levels, cultural beliefs, identical educational backgrounds, and comparable health-seeking habits. However, it was higher than previous research done in Iraq44% [51], in Indonesia 43.4% [47], in Pakistan39% [52], in pakistan43.8% [34], and in Iran31.7% [33]. This high percentage can be explained by socio-demographic factors or by weak or inefficient measures implemented by the competent healthcare authorities in East African regions. Those regions are unstable as a result of natural disasters and conflict, and they also have poor accessibility and availability of health-related services. It might be the poor state of many health systems in East Africa and their declining capacities to lead cancer preventive initiatives and respond to the overall health needs of the population, as compared to developed countries, are also major concerns [53, 54].

This systematic review and meta-analysis revealed significant heterogeneity among the included studies. The variation is due to data collection methods, measurement of delayed presentation breast cancer, sample size representativeness, regional difference, cultural difference, and quality of the included variables. Addressing these inconsistencies will enhance the comparability of the studies and improve the reliability of the conclusion drawn from this meta-analysis.

The subgroup analysis of the study between countries indicated that the highest level of delayed presentation of breast cancer was in Sudan (74.6%). This is higher than a systematic review and meta-analysis done in Africa54% [11].The possible explanation might be a low level of awareness about health-seeking behavior, socio-cultural factors, small sample size, and study design differences.

In this meta-analysis the contributing factors were the age of more than40 years, illiterate/low level of education, rural residence,>5km away from the health facility, visiting traditional healer and not feeling breast pain were significantly associated with delayed presentation of a breast cancer patient.

This review found that those age>40 years were more likely to delay the presentation of breast cancer than their counterparts. This is consistent with a study done in Pakistan [52], in the United Kingdom [55], in Saudi [31], in Nigeria [49], in the Middle East [19] and Estonia [56].The possible reason was that age advances decreased health-seeking behavior and prioritized other health issues over breast cancer screening and treatment. There may be a lack of autonomy and fear of sharing the problems with health care provider [30–32].However, it contradicts earlier studies [33, 57], because older patients may be anxious about various comorbidities and quickly referred to health institution [58].

These review findings show that illiterate/low level of education breast cancer patients had a stronger association with delayed presentation than educated ones. This is similar to prior studies done in Iraq [51], systematic reviews, and meta-analyses done in different countries [10, 18–21]and in Pakistan [32, 52, 57]. The potential explanation of low education is not being aware of the symptoms of breast problems, the belief that symptoms go away by themselves [59], the severity of the disease, and cultural intervention. More if the participant is not educated less likely to disclose the symptoms to friends and health care providers as a result of the delay of presentation of breast cancer. Additionally, higher education levels might increase the likelihood of comprehending the health campaign messages with terminology that is not representative of local dialects.

Moreover, this meta-analysis found that rural residence had a strong association with delayed presentation of breast cancer. These figures are similar to a study done in Saudi [31] and in Pakistan [57].The justification is the rural part of East Africa region had a low level of awareness about health-seeking consultation and poor healthcare services(accessibility, availability) [29, 30, 34] and they are not near for information. Plus, women who come from rural countries may have difficulty with transportation to a nearby health center, and traveling a long distance to get an appropriate diagnosis, which in turn may result in delayed presentation.

This meta-analysis also found that not feeling/absence of breast pain was more likely to delay the presentation of breast cancer than that of counterparts. This is similar to a study done in Iraq [51], in Estonia [56], in Palestinian [60], and in Saudi [31].The possible reason was patient their breast is asymptomatic they can’t appreciate the disease and they believe that mass without pain is normal physiology and resolves spontaneously. This is also correlated with breast self-examination is important for early detection and decreasing delayed presentation [61].

Furthermore, the review found that participants who visit traditional healers had a strong association with delayed presentation of breast cancer. This is supported by prior studies [11, 21–23].The explanation was they perceived traditional healers were more curative than modern medicine and patients wasted their time with traditional medicine. In addition, because of fear of surgery of the breast and false belief [30–32], they are abstaining from the health institution for health care services. So, while taking those remedies, most patients delay coming to the health facility leading to worsening of symptoms and advanced stage.

The final significant factor for this research found that distance >5km from the health facility was a significant factor with delay presentation of breast cancer patients. It has been reported that East African women living far from health institutions are particularly vulnerable to late presentation breast cancer, partially due to the high cost of transportation [30], low socio-economic status [18, 33], transportation problem [30] and waste time by long journeys to reach health care facilities.

Strength of the study

Strengths of this study include our rigorous review of existing published literature. An assessment of study quality and heterogeneity, providing insight into the reliability of the findings and compressive synthesis of evidence.

Limitations of the study

One of the limitations of the study is the fact that recall bias may not have been eliminated from the study, as almost all studies included in the study were cross-sectional and it is possible that the outcome variable was under- or overestimated. The findings of this meta-analysis should be done with due consideration of the substantial heterogeneity between included studies. The high heterogeneity indicates that the studies are not sufficiently similar to combine meaningfully, leading to potentially misleading conclusions. Studies that were published only in the English language were taken into account.

We suggest for future researchers the inclusion of diverse study designs, focus on subgroup analysis, and improved statistical techniques for handling heterogeneity and missing data, it is better to take a qualitative approach and also include articles published in different languages.

Conclusion

This meta-analysis found that over half of breast cancer patients in East Africa experience delays in the presentation of breast cancer. Significant factors associated with delayed presentation include age over 40 years, illiteracy, rural residence, use of traditional healers, distance greater than 5 km from a health facility, and absence of breast pain. These results highlight the critical need for targeted public health interventions to address these barriers. Healthcare stakeholders and policymakers focus on enhancing awareness, improving education, and increasing healthcare access are essential to reduce delays and improve early detection and treatment of breast cancer in East Africa.

Supporting information

S1 File. The PRISMA checklist.

(DOCX)

pone.0309792.s001.docx^{(35.1KB, docx)}

S2 File. Newcastle-Ottawa quality assessment scale for cross-sectional studies used in the systematic review and meta-analysis 2024.

(DOCX)

pone.0309792.s002.docx^{(13.8KB, docx)}

S3 File. Searching strategy.

(DOCX)

pone.0309792.s003.docx^{(15.4KB, docx)}

S4 File. Description of inclusion/exclusion articles.

(DOCX)

pone.0309792.s004.docx^{(22.3KB, docx)}

S5 File. Data extraction of included articles in the systematic review and meta- analysis.

(DOCX)

pone.0309792.s005.docx^{(14.5KB, docx)}

S6 File. Characteristics of the included articles.

(DOCX)

pone.0309792.s006.docx^{(15.3KB, docx)}

Acknowledgments

We acknowledge Woldia University for the provision of internet service to conduct this meta-analysis.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

References

1.Arnold M., Morgan E., Rumgay H., Mafra A., Singh D., Laversanne M., et al.: ‘Current and future burden of breast cancer: Global statistics for 2020 and 2040’, The Breast, 2022, 66, pp. 15–23 [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Ghoncheh M., Mohammadian-Hafshejani A., and Salehiniya H.: ‘Incidence and mortality of breast cancer and their relationship to development in Asia’, Asian Pacific Journal of Cancer Prevention, 2015, 16, (14), pp. 6081–6087 [DOI] [PubMed] [Google Scholar]
3.Ethiopia A.A.: ‘World Health Organization (2015) Cancer–a growing public health concern for Ethiopia ‘ , WHO, Africa Region, 2015 [Google Scholar]
4.Clegg-Lamptey, J.-N.: ‘Epidemiology Of Breast Cancer In Africa’, Africa Region, 2017
5.Korir A., Okerosi N., Ronoh V., Mutuma G., and Parkin M.: ‘Incidence of cancer in N airobi, K enya (2004–2008)’, I nternational journal of cancer, 2015, 137, (9), pp. 2053–2059 [DOI] [PubMed] [Google Scholar]
6.Chokunonga E., Borok M., Chirenje Z., Nyakabau A., and Parkin D.: ‘Trends in the incidence of cancer in the black population of Harare, Zimbabwe 1991–2010’, International journal of cancer, 2013, 133, (3), pp. 721–729 doi: 10.1002/ijc.28063 [DOI] [PubMed] [Google Scholar]
7.Wabinga H.R., Nambooze S., Amulen P.M., Okello C., Mbus L., and Parkin D.M.: ‘Trends in the incidence of cancer in Kampala, Uganda 1991–2010’, International journal of cancer, 2014, 135, (2), pp. 432–439 [DOI] [PubMed] [Google Scholar]
8.Anderson B.O., Ilbawi A.M., Fidarova E., Weiderpass E., Stevens L., Abdel-Wahab M., et al.: ‘The Global Breast Cancer Initiative: a strategic collaboration to strengthen health care for non-communicable diseases’, The Lancet Oncology, 2021, 22, (5), pp. 578–581 [DOI] [PubMed] [Google Scholar]
9.WHO: ‘WHO,global breast cancer initative ‘, 2022 [Google Scholar]
10.A, C.E.P.: ‘Delayed presentation and diagnosis of breast cancer in African women: a systematic review’, Annals of Epidemiology, 2017, 27 [DOI] [PMC free article] [PubMed] [Google Scholar]
11.S, O.: ‘Prevalence of Themes Linked to Delayed Presentation of Breast Cancer in Africa: AMeta-Analysis of Patient-Reported Studies’, JCO Global Oncol 2020, 6 [DOI] [PMC free article] [PubMed] [Google Scholar]
12.Richards M., Westcombe A., Love S., Littlejohns P., and Ramirez A.: ‘Influence of delay on survival in patients with breast cancer: a systematic review’, The Lancet, 1999, 353, (9159), pp. 1119–1126 [DOI] [PubMed] [Google Scholar]
13.Robinson E., Mohilever J., and Borovik R.: ‘Factors affecting delay in diagnosis of breast cancer: relationship of delay to stage of disease’, Israel journal of medical sciences, 1986, 22, (5), pp. 333–338 [PubMed] [Google Scholar]
14.Burgess C., Ramirez A., Richards M., and Love S.: ‘Who and what influences delayed presentation in breast cancer?’, British journal of cancer, 1998, 77, (8), pp. 1343–1348 doi: 10.1038/bjc.1998.224 [DOI] [PMC free article] [PubMed] [Google Scholar]
15.Afzelius P., Zedeler K., Sommer H., Mouridsen H.T., and Blichert-Toft M.: ‘Patient’s and doctor’s delay in primary breast cancer: Prognostic implications ’, Acta Oncologica, 1994, 33, (4), pp. 345–351 [DOI] [PubMed] [Google Scholar]
16.Richards M., Smith P., Ramirez A., Fentiman I., and Rubens R.: ‘The influence on survival of delay in the presentation and treatment of symptomatic breast cancer’, British journal of cancer, 1999, 79, (5), pp. 858–864 doi: 10.1038/sj.bjc.6690137 [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Macarthur C., and Smith A.: ‘DELAY IN BREAST CANCER AND THE NATURE OF PRESENTING SYMPTOMS’, The Lancet, 1981, 317, (8220), pp. 601–603 doi: 10.1016/s0140-6736(81)92044-4 [DOI] [PubMed] [Google Scholar]
18.Sharma K.: ‘A Systematic Review of Barriers to Breast Cancer Care in Developing Countries Resulting in Delayed Patient Presentation’, Journal of Oncology, 2012 [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Alhurishi S.: ‘Factors Influencing Late Presentation for Breast Cancer in the Middle East: A Systematic Review’, Asian Pacific J Cancer Prev, 2011, 12 [PubMed] [Google Scholar]
20.Agodirin O.: ‘Determinants of Delayed Presentation and Advanced-Stage Diagnosis of Breast Cancer in Africa: A Systematic Review and Meta-Analysis’, Asian Pac J Cancer Prev, 2021, 22 [DOI] [PMC free article] [PubMed] [Google Scholar]
21.Petrova D.: ‘Duration of the patient interval in breast cancer and factors associated with longer delays in low‐and middle‐income countries: A systematic review with meta‐analysis’, Psycho‐Oncology, 2022, 32, (13), pp. 24. [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Donkor A.: ‘Factors Contributing to Late Presentation of Breast Cancer in Africa: A Systematic Literature Review’, ARCHIVES OF MEDICINE, 2015, 8, (2) [Google Scholar]
23.Akuoko C.P.: ‘Barriers to early presentation and diagnosis of breast cancer among African women living in sub-Saharan Africa’, PLOS ONE, 2017, 10 [DOI] [PMC free article] [PubMed] [Google Scholar]
24.Sobri F.B.: ‘Factors Affecting Delayed Presentation and Diagnosis of Breast Cancer in Asian Developing Countries Women: A Systematic Review’, Asian Pac J Cancer Prev, 2021, 22 [DOI] [PMC free article] [PubMed] [Google Scholar]
25.Jones Claire EL: ‘A systematic review of barriers to early presentation and diagnosis with breast cancer among black women’, BMJ OPEN, 2014, 4 [DOI] [PMC free article] [PubMed] [Google Scholar]
26.Montazeri A., Ebrahimi M., Mehrdad N., Ansari M., and Sajadian A.: ‘Delayed presentation in breast cancer: a study in Iranian women’, BMC women’s health, 2003, 3, pp. 1–6 [DOI] [PMC free article] [PubMed] [Google Scholar]
27.Odongo J., Makumbi T., Kalungi S., and Galukande M.: ‘Patient delay factors in women presenting with breast cancer in a low income country’, BMC research notes, 2015, 8, pp. 1–6 [DOI] [PMC free article] [PubMed] [Google Scholar]
28.Ibrahim N., and Oludara M.: ‘Socio-demographic factors and reasons associated with delay in breast cancer presentation: a study in Nigerian women’, The Breast, 2012, 21, (3), pp. 416–418 [DOI] [PubMed] [Google Scholar]
29.Harirchi I., Ghaemmaghami F., Karbakhsh M., Moghimi R., and Mazaherie H. : ‘Patient delay in women presenting with advanced breast cancer: an Iranian study’, Public health, 2005, 119, (10), pp. 885–891 [DOI] [PubMed] [Google Scholar]
30.Čačala S.R., and Gilart J.: ‘Factors relating to late presentation of patients with breast cancer in Area 2 KwaZulu-Natal, South Africa’, Journal of Global Oncology, 2017, 3, (5), pp. 497–501 [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Altwalbeh D., El Dahshan M., and Yassin R.: ‘Factors influencing delayed presentation of breast cancer among Saudi women’, International Journal of Science and Research, 2015, 1, (4), pp. 967–974 [Google Scholar]
32.Shamsi U., Khan S., Azam I., Usman S., Maqbool A., Gill T., et al.: ‘Patient delay in breast cancer diagnosis in two hospitals in Karachi, Pakistan: preventive and life-saving measures needed’, JCO Global Oncology, 2020, 6, pp. 873–883 doi: 10.1200/GO.20.00034 [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Harirchi I., Karbakhsh M., Hadi F., Madani S.S., Sirati F., and Kolahdoozan S.: ‘Patient delay, diagnosis delay and treatment delay for breast cancer: comparison of the pattern between patients in public and private health sectors’, Archives of Breast Cancer, 2015, pp. 52–57 [Google Scholar]
34.Baig M., Sohail I., Altaf H.N., and Altaf O.S.: ‘Factors influencing delayed presentation of breast cancer at a tertiary care hospital in Pakistan’, Cancer Reports, 2019, 2, (1), pp. e1141. [DOI] [PMC free article] [PubMed] [Google Scholar]
35.Stapleton J.M., Mullan P.B., Dey S., Hablas A., Gaafar R., Seifeldin I.A., et al. :Patient‐mediated factors predicting early‐and late‐stage presentation of breast cancer in Egypt’, Psycho‐Oncology, 2011, 20, (5), pp. 532–537 doi: 10.1002/pon.1767 [DOI] [PMC free article] [PubMed] [Google Scholar]
36.Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., et al. : ‘The PRISMA 2020 statement: an updated guideline for reporting systematic reviews’, International journal of surgery, 2021, 88, pp. 105906 doi: 10.1016/j.ijsu.2021.105906 [DOI] [PubMed] [Google Scholar]
37.Downes M.J.: ‘Development of a critical appraisal tool to assess the quality of cross-sectional studies (AXIS’, BMJ Open, 2016, 6 doi: 10.1136/bmjopen-2016-011458 [DOI] [PMC free article] [PubMed] [Google Scholar]
38.Hassen A.M., Hussien F.M., Asfaw Z.A., and Assen H.E.: ‘Factors associated with delay in breast cancer presentation at the only oncology center in North East Ethiopia: a cross-sectional study’, Journal of multidisciplinary healthcare, 2021, pp. 681–694 [DOI] [PMC free article] [PubMed] [Google Scholar]
39.Tesfaw A., Demis S., Munye T., and Ashuro Z.: ‘Patient delay and contributing factors among breast cancer patients at two cancer referral centres in Ethiopia: a cross-sectional study’, Journal of Multidisciplinary Healthcare, 2020, pp. 1391–1401 [DOI] [PMC free article] [PubMed] [Google Scholar]
40.Shewarega B., Getachew S., Assefa N., Yesufe A., Trabizsch J., Dandena Y., et al. : ‘Predictors of advanced-stage presentation among breast and cervical cancer patients in Ethiopia’, medRxiv, 2023, pp. 2023.2012. 2016. doi: 10.1074/jbc.M112.435909 [DOI] [PMC free article] [PubMed] [Google Scholar]
41.Muhammed J.A., Kroeber E.S., Deribe B., Unverzagt S., Taylor L., Aynalem A., et al.: ‘Prevalence and Factors Associated With Delay in Presentation of Breast Cancer Patients in Ethiopia: A Cross-Sectional Institution-Based Study’, medRxiv, 2022, pp. 2022.2011. 2001.22281792 [Google Scholar]
42.Gebremariam A., Addissie A., Worku A., Assefa M., Pace L.E., Kantelhardt E.J., et al. : ‘Time intervals experienced between first symptom recognition and pathologic diagnosis of breast cancer in Addis Ababa, Ethiopia: a cross-sectional study’, BMJ open, 2019, 9, (11), pp. e032228. [DOI] [PMC free article] [PubMed] [Google Scholar]
43.Abiye M., Assefa A., and Mohammedsani B.: ‘Delay And Contributing Factors In Patients With Breast Cancer At Hiwot Fana Comprehensive Specialized Hospital, Harar, Eastern Ethiopia’, Haramaya University Harar, 2023 [Google Scholar]
44.Pace L.E., Mpunga T., Hategekimana V., Dusengimana J.-M.V., Habineza H., Bigirimana J.B., et al. : ‘Delays in breast cancer presentation and diagnosis at two rural cancer referral centers in Rwanda’, The oncologist, 2015, 20, (7), pp. 780–788 [DOI] [PMC free article] [PubMed] [Google Scholar]
45.Salih A.M., Alfaki M.M., Alam-Elhuda D.M., and Nouradyem M.M.: ‘Factors delaying presentation of Sudanese breast cancer patients: an analysis using Andersen’s model’, Asian Pacific Journal of Cancer Prevention, 2016, 17, (4), pp. 2105–2110 [DOI] [PubMed] [Google Scholar]
46.Egger M., Davey Smith G., Schneider M., and Minder C.: ‘Bias in meta-analysis detected by a simple, graphical test’, BMJ (Clinical research ed.), 1997, 315, (7109), pp. 629–634 doi: 10.1136/bmj.315.7109.629 [DOI] [PMC free article] [PubMed] [Google Scholar]
47.Hutajulu S.H., Prabandari Y.S., Bintoro B.S., Wiranata J.A., Widiastuti M., Suryani N.D., et al.: ‘Delays in the presentation and diagnosis of women with breast cancer in Yogyakarta, Indonesia: a retrospective observational study’, PloS one, 2022, 17, (1), pp. e0262468. [DOI] [PMC free article] [PubMed] [Google Scholar]
48.Awofeso O., Roberts A.A., Salako O., Balogun L., and Okediji P.: ‘Prevalence and pattern of late-stage presentation in women with breast and cervical cancers in Lagos University Teaching Hospital, Nigeria’, Nigerian Medical Journal, 2018, 59, (6), pp. 74–79 doi: 10.4103/nmj.NMJ_112_17 [DOI] [PMC free article] [PubMed] [Google Scholar]
49.Elenwo S.N., Ijah R.F.O.A., and Dimoko A.A.: ‘Factors associated with late presentation of breast cancer in a Teaching Hospital in Port Harcourt, Nigeria’, Nigerian Health Journal, 2022, 22, (1), pp. 140–152 [Google Scholar]
50.Thakur N., Humne A., and Godale L.: ‘Delay in presentation to the hospital and factors affecting it in breast cancer patients attending tertiary care center in Central India’, Indian journal of cancer, 2015, 52, (1), pp. 102–105 [DOI] [PubMed] [Google Scholar]
51.Abdulkareem A.A., Ghalib H.A., and Rashaan M.I.: ‘Factors Causing Delayed Presentations of Breast Cancer among Female patients in Sulaimaniyah Governorate, Iraq’, 2023 [DOI] [PMC free article] [PubMed] [Google Scholar]
52.Khan M.A., Hanif S., Iqbal S., Shahzad M.F., Shafique S., and Khan M.T.: ‘Presentation delay in breast cancer patients and its association with sociodemographic factors in North Pakistan’, Chinese Journal of Cancer Research, 2015, 27, (3), pp. 288. [DOI] [PMC free article] [PubMed] [Google Scholar]
53.Gbenonsi G., Boucham M., Belrhiti Z., Nejjari C., Huybrechts I., and Khalis M.: ‘Health System Factors That Influence Treatment Delay in Women With Breast Cancer in Sub-saharan Africa: A Systematic Review ’, 2021 [DOI] [PMC free article] [PubMed] [Google Scholar]
54.Gbenonsi G., Boucham M., Belrhiti Z., Nejjari C., Huybrechts I., and Khalis M.: ‘Health system factors that influence diagnostic and treatment intervals in women with breast cancer in sub-Saharan Africa: a systematic review’, BMC Public Health, 2021, 21, pp. 1–20 [DOI] [PMC free article] [PubMed] [Google Scholar]
55.Simon A.E., Waller J., Robb K., and Wardle J.: ‘Patient delay in presentation of possible cancer symptoms: the contribution of knowledge and attitudes in a population sample from the United Kingdom’, Cancer Epidemiology, Biomarkers & Prevention, 2010, 19, (9), pp. 2272–2277 [DOI] [PMC free article] [PubMed] [Google Scholar]
56.Innos K., Padrik P., Valvere V., Eelma E., Kütner R., Lehtsaar J., et al. : ‘Identifying women at risk for delayed presentation of breast cancer: a cross-sectional study in Estonia’, BMC Public Health, 2013, 13, pp. 1–7 [DOI] [PMC free article] [PubMed] [Google Scholar]
57.Gulzar F., Akhtar M.S., Sadiq R., Bashir S., Jamil S., and Baig S.M.: ‘Identifying the reasons for delayed presentation of Pakistani breast cancer patients at a tertiary care hospital’, Cancer management and research, 2019, pp. 1087–1096 [DOI] [PMC free article] [PubMed] [Google Scholar]
58.Macleod U.: ‘Risk factors for delayed presentation and referral of symptomatic cancer: evidence for common cancers’, British Journal of Cancer, 2019, 19. [DOI] [PMC free article] [PubMed] [Google Scholar]
59.Nosarti C.: ‘ Delay in presentation symptomatic referals to breast clinic:patient and system factors’, British Journal of Cancer (2015, 82, (3) [DOI] [PMC free article] [PubMed] [Google Scholar]
60.Al-Shiekh S.S.A.: ‘Factors affecting delay in the presentation of breast cancer symptoms among women in Gaza, occupied Palestinian territory: a cross-sectional survey’, BMJopen, 2022, 12 [DOI] [PMC free article] [PubMed] [Google Scholar]
61.Black E.: ‘Improving early detection of breast cancer in sub-Saharan Africa: why mammography may not be the way forward’, Black and Richmond Globalization and Health 2019, 15, (3) [DOI] [PMC free article] [PubMed] [Google Scholar]

PLoS One. doi: 10.1371/journal.pone.0309792.r001

Decision Letter 0

Wenjie Shi

7 Jul 2024

PONE-D-24-14681Delayed Presentation of Breast Cancer Patients and Contributing Factors in East Africa: Systematic Review and Meta- Analysis.PLOS ONE

Dear Dr. Mulugeta,

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Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #4: Yes

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Reviewer #1: This study, a systematic review and meta-analysis, examined the prevalence and contributing factors of delayed presentation among breast cancer patients in East Africa and found that more than half of patients experienced delayed diagnosis, which was significantly associated with factors such as age, education level, place of residence and visits to traditional healers. However, there are several issues that need to be addressed before the paper can be considered for publication.

1) Does the study cover all countries in East Africa or is it limited to certain countries?

2) Does the study include the most recent data or is it limited to a specific time period?

3) Did the study consider the impact of socioeconomic status on the behaviour of delayed medical seeking?

4) Did the study examine the effect of access to health care on delayed medical consultation?

5) Did the study analyse the impact of culture and beliefs on the behaviour of delayed medical consultation?

6) Did the study consider the impact of the diagnostic capabilities of different health care facilities on delayed diagnosis?

7) Did the study assess the impact of patients' knowledge about breast cancer on their behaviour in seeking medical care?

8) Does the study consider the impact of patients' self-perception of symptoms on their health care seeking behaviour?

9) The manuscript should be proofread for grammatical errors, spelling mistakes or unclear presentation.

10) The methods section should be more precise, detailed and scientific.

Reviewer #2: General Comments:

The manuscript presents a systematic review and meta-analysis on the delayed presentation of breast cancer patients in East Africa, identifying key factors contributing to late presentation. This is a significant and timely topic, given the high mortality associated with breast cancer in the region. The study follows a rigorous methodological approach and provides valuable insights. However, several areas require major revisions to improve the clarity, robustness, and overall quality of the manuscript.

Major Revisions:

1. Abstract Clarity and Conciseness:

o The abstract should be more concise and clearly highlight the key findings and their implications. It currently includes repetitive information and lacks a clear structure.

o The results section in the abstract should provide specific statistics on delay prevalence and the most significant factors contributing to the delay, rather than a general overview.

2. Introduction:

o The introduction section is lengthy and contains excessive background information. Condense it to focus more on the rationale for the study, specific research questions, and the study's significance.

o Some of the statistics and details can be moved to a background subsection if necessary.

3. Methods:

o Search Strategy: The search strategy section is comprehensive but lacks clarity in describing the inclusion and exclusion criteria. Consider using a table to summarize these criteria for better readability.

o Quality Assessment: More detail is needed on how the Newcastle-Ottawa Scale was applied and the criteria used for assessing the quality of included studies. A table summarizing the quality scores of the included studies would be helpful.

4. Results:

o The results section should present the key findings more clearly, with distinct subsections for different aspects of the study (e.g., prevalence of delayed presentation, factors contributing to the delay).

5. Discussion:

o The discussion should provide a deeper analysis of the results, comparing them with findings from other regions or previous studies. Discuss the implications of the high prevalence of delayed presentation and the identified factors in more detail.

o Highlight the strengths and limitations of the study more explicitly. Discuss how the limitations might have affected the results and suggest areas for future research.

6. Conclusion:

o The conclusion should be more focused on summarizing the key findings and their implications for public health policies and interventions in East Africa.

o Avoid introducing new information in the conclusion section.

7. Overall Language and Style:

o The manuscript would benefit from a thorough proofreading to correct grammatical errors and improve the overall readability. Some sentences are overly complex and could be simplified.

Specific Comments:

1. Abstract:

o "The overall analysis of delay presentation breast cancer patient was 61.85%..." should be rephrased for clarity.

o Results should be summarized with specific data points and concise explanations.

2. Introduction:

o Condense the first two paragraphs to avoid redundancy. Focus on the unique context of East Africa.

o The last paragraph of the introduction should clearly state the study objectives and research questions.

3. Methods:

o Clarify the search terms and databases used. Consider presenting the search strategy in a table.

o Provide a rationale for the selection of studies based on the Newcastle-Ottawa Scale.

4. Results:

o The PRISMA flow diagram should be included to illustrate the study selection process.

o Present the findings related to each factor contributing to the delay in separate subsections or a summary table.

5. Discussion:

o Compare the study’s findings with those of similar studies from other regions.

o Discuss potential reasons for the high prevalence of delayed presentation in East Africa.

6. Conclusion:

o Emphasize the need for targeted interventions and policy changes based on the study’s findings.

o Suggest practical steps for healthcare providers and policymakers to reduce delayed presentations.

Conclusion:

The manuscript addresses an important public health issue and provides valuable data on the delayed presentation of breast cancer patients in East Africa. However, significant revisions are necessary to improve the clarity, structure, and depth of the analysis. With these improvements, the manuscript has the potential to make a substantial contribution to the field.

Reviewer #3: Reviewer Comments:

The manuscript titled "Factors Contributing to Late Presentation of Breast Cancer in East Africa: A Systematic Review and Meta-Analysis" presents a comprehensive investigation into a critical public health issue. The study is timely, given the rising global incidence and mortality rates of breast cancer, particularly in less developed regions like East Africa.

1. The introduction effectively contextualizes the significance of the study within the broader global health landscape. It clearly articulates the urgency of addressing late presentations of breast cancer in East Africa, which is essential for guiding future interventions and policies.

2.The authors adhered to the PRISMA guidelines meticulously, ensuring transparency and reproducibility in their systematic review and meta-analysis. The search strategy was robust, encompassing multiple databases and employing comprehensive search terms relevant to the study objectives.

3.The analysis of data regarding the prevalence of late patient presentations and associated factors was thorough and well-documented. The inclusion of quality assessment criteria and the justification for study selection criteria added to the credibility of the findings.

4.The discussion effectively synthesizes the findings, providing insights into the implications for breast cancer management and public health strategies in East Africa. It appropriately discusses the limitations of the study and suggests avenues for future research.

5. The character of the included studies needs to be described in detail.

The manuscript is generally well-written and organized, though some sections could benefit from minor revisions for clarity and flow. Attention to enhancing the coherence between sections and refining language to improve readability would further strengthen the manuscript.

Reviewer #4: The authors reported about the delayed presentation of breast cancer patients and contributing factors in East Africa.

We need to know if there any updated data after 2020 in Background section.

And it is necessary to explain the heterogeneity in the Discussion section.

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Reviewer #1: Yes: Xiaodong Zou

Reviewer #2: Yes: Yan Li

Reviewer #3: No

Reviewer #4: No

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PLoS One. 2024 Nov 11;19(11):e0309792. doi: 10.1371/journal.pone.0309792.r002

Author response to Decision Letter 0

28 Jul 2024

Thank you dear editors and reviewers for your valuable comments. Based on your comment we submit the response entitled by Response to reviewers in the submissions system. The responses to the reviewers' comments and suggestions have been highlighted in blue and the main document of the manuscript in yellow for better assessment.

Attachment

Submitted filename: Response to Reviewers.docx

pone.0309792.s007.docx^{(70.2KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0309792.r003

Decision Letter 1

Wenjie Shi

7 Aug 2024

PONE-D-24-14681R1Delayed Presentation of Breast Cancer Patients and Contributing Factors in East Africa: Systematic Review and Meta- Analysis.PLOS ONE

Dear Dr. Mulugeta,

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. Please submit your revised manuscript by Sep 21 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Wenjie Shi

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

please make revisions according to Review 2's comments

[Note: HTML markup is below. Please do not edit.]

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

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

6. Review Comments to the Author

Reviewer #1: In the revised manuscript, the authors have addressed all my concerns in a very convincing manner. As such I support the publication of this original article in PLOS ONE.

Reviewer #2: Overall Evaluation

The paper provides a comprehensive analysis of the potential for using mRNA expression data to predict biochemical recurrence (BCR) in prostate cancer (PCa) patients pre-operatively. The use of machine learning methodologies to model time-to-event data is innovative and demonstrates significant improvements in predictive performance compared to traditional clinical models. The study is well-structured and the methodology is sound, however, there are several areas where the paper could benefit from additional clarification and minor revisions.

Major Strengths

1. Innovative Approach: The use of mRNA expression data pre-operatively for BCR prediction in PCa is novel and holds promise for improving patient outcomes.

2. Comprehensive Methodology: The paper employs a range of machine learning models and provides a thorough evaluation of their performance using multiple metrics.

3. Clinical Relevance: The focus on pre-operative prediction aligns well with the clinical need for early and accurate decision-making in prostate cancer treatment.

Minor Revisions

1. Clarification of Calibration Methodology:

o The paper describes two forms of calibration analyses but the explanation of the calibration curves and how they were derived is somewhat dense. Consider breaking down the steps more clearly, perhaps with additional visual aids or flowcharts to guide the reader through the process.

o Specifically, provide more detailed explanations on how the Kaplan-Meier estimates were used in the calibration curves and the rationale behind using the quintiles.

2. Detailed Explanation of Feature Selection:

o While the study discusses the feature selection rates, there is limited discussion on why certain mRNA variables were selected over others. A deeper analysis of the biological relevance of the frequently selected mRNA variables (e.g., DNAH8, ABCC11, ESM1) and their known roles in PCa or other cancers would strengthen the discussion.

o It would be beneficial to include a table summarizing the key mRNA variables, their known functions, and any previous associations with cancer to provide context to their selection.

3. Discussion of Model Limitations:

o The paper acknowledges the modest cohort size and single-centre data source as limitations. It would be useful to discuss potential biases that might arise from this and how they might impact the generalizability of the results.

o Consider elaborating on how multi-centre validation could address these limitations and the specific steps that will be taken in future research to ensure robustness and applicability across diverse populations.

4. Figure Improvements:

o Figures 1 and 2 are crucial for understanding the calibration performance of the models but could benefit from higher resolution and clearer labels. Ensure that all axes and legends are easy to read.

o In Figure 5, it would be helpful to add more context or annotations to highlight key observations regarding the expression levels of mRNA variables in patients receiving neoadjunctive therapy versus those who did not.

5. ROC and DCA Analysis:

o The ROC and DCA analyses are well-presented but could be further enhanced by including confidence intervals for the AUC values in the ROC plots directly, rather than just in the table. This visual representation would make it easier to compare the performance across models.

o In the DCA plots, consider adding a brief explanation of how net benefit is interpreted and its clinical implications, as some readers may not be familiar with this analysis.

6. Discussion on Clinical Implementation:

o The conclusion mentions the potential for clinical integration of these models but does not elaborate on the practical steps required to achieve this. Provide more details on what would be needed for these models to be adopted in a clinical setting, including any regulatory considerations, necessary validation studies, and potential barriers to implementation.

Conclusion

This paper presents a significant contribution to the field of prostate cancer research by demonstrating the potential of mRNA-based pre-operative prediction models. With minor revisions to enhance clarity, provide deeper biological insights, and discuss implementation strategies, this study could offer valuable guidance for the development of precision medicine tools in oncology.

Reviewer #3: (No Response)

Reviewer #4: (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: Yes: Xiaodong Zou

Reviewer #2: Yes: Yan Li

Reviewer #3: No

Reviewer #4: No

**********

PLoS One. 2024 Nov 11;19(11):e0309792. doi: 10.1371/journal.pone.0309792.r004

Author response to Decision Letter 1

12 Aug 2024

Dear reviewer great thanks for your continuous support for the improvement of our manuscript. The response of our manuscript was sent by the system.

Attachment

Submitted filename: Response to Reviewer.docx

pone.0309792.s008.docx^{(18.1KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0309792.r005

Decision Letter 2

Wenjie Shi

20 Aug 2024

Delayed Presentation of Breast Cancer Patients and Contributing Factors in East Africa: Systematic Review and Meta- Analysis.

PONE-D-24-14681R2

Dear Dr. Mulugeta,

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.

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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,

Wenjie Shi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: Yes

**********

6. Review Comments to the Author

Reviewer #2: The revised manuscript presents a well-conducted systematic review and meta-analysis on the delayed presentation of breast cancer patients in Eastern Africa. The study provides a comprehensive evaluation of the prevalence of delayed presentation and identifies key factors associated with these delays. Overall, the manuscript is methodologically sound and offers valuable insights into a critical public health issue. I recommend accepting the manuscript for publication with minor revisions to address the following specific comments.

**********

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 #2: Yes: Yan Li

**********

PLoS One. doi: 10.1371/journal.pone.0309792.r006

Acceptance letter

Wenjie Shi

4 Sep 2024

PONE-D-24-14681R2

PLOS ONE

Dear Dr. Mulugeta,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

* There are no issues that prevent the paper from being properly typeset

If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps.

Lastly, 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 customercare@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

Prof. Wenjie Shi

Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 File. The PRISMA checklist.

(DOCX)

pone.0309792.s001.docx^{(35.1KB, docx)}

S2 File. Newcastle-Ottawa quality assessment scale for cross-sectional studies used in the systematic review and meta-analysis 2024.

(DOCX)

pone.0309792.s002.docx^{(13.8KB, docx)}

S3 File. Searching strategy.

(DOCX)

pone.0309792.s003.docx^{(15.4KB, docx)}

S4 File. Description of inclusion/exclusion articles.

(DOCX)

pone.0309792.s004.docx^{(22.3KB, docx)}

S5 File. Data extraction of included articles in the systematic review and meta- analysis.

(DOCX)

pone.0309792.s005.docx^{(14.5KB, docx)}

S6 File. Characteristics of the included articles.

(DOCX)

pone.0309792.s006.docx^{(15.3KB, docx)}

Attachment

Submitted filename: Response to Reviewers.docx

pone.0309792.s007.docx^{(70.2KB, docx)}

Attachment

Submitted filename: Response to Reviewer.docx

pone.0309792.s008.docx^{(18.1KB, docx)}

Data Availability Statement

All relevant data are within the manuscript and its Supporting Information files.

[pone.0309792.ref001] 1.Arnold M., Morgan E., Rumgay H., Mafra A., Singh D., Laversanne M., et al.: ‘Current and future burden of breast cancer: Global statistics for 2020 and 2040’, The Breast, 2022, 66, pp. 15–23 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref002] 2.Ghoncheh M., Mohammadian-Hafshejani A., and Salehiniya H.: ‘Incidence and mortality of breast cancer and their relationship to development in Asia’, Asian Pacific Journal of Cancer Prevention, 2015, 16, (14), pp. 6081–6087 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref003] 3.Ethiopia A.A.: ‘World Health Organization (2015) Cancer–a growing public health concern for Ethiopia ‘ , WHO, Africa Region, 2015 [Google Scholar]

[pone.0309792.ref004] 4.Clegg-Lamptey, J.-N.: ‘Epidemiology Of Breast Cancer In Africa’, Africa Region, 2017

[pone.0309792.ref005] 5.Korir A., Okerosi N., Ronoh V., Mutuma G., and Parkin M.: ‘Incidence of cancer in N airobi, K enya (2004–2008)’, I nternational journal of cancer, 2015, 137, (9), pp. 2053–2059 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref006] 6.Chokunonga E., Borok M., Chirenje Z., Nyakabau A., and Parkin D.: ‘Trends in the incidence of cancer in the black population of Harare, Zimbabwe 1991–2010’, International journal of cancer, 2013, 133, (3), pp. 721–729 doi: 10.1002/ijc.28063 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref007] 7.Wabinga H.R., Nambooze S., Amulen P.M., Okello C., Mbus L., and Parkin D.M.: ‘Trends in the incidence of cancer in Kampala, Uganda 1991–2010’, International journal of cancer, 2014, 135, (2), pp. 432–439 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref008] 8.Anderson B.O., Ilbawi A.M., Fidarova E., Weiderpass E., Stevens L., Abdel-Wahab M., et al.: ‘The Global Breast Cancer Initiative: a strategic collaboration to strengthen health care for non-communicable diseases’, The Lancet Oncology, 2021, 22, (5), pp. 578–581 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref009] 9.WHO: ‘WHO,global breast cancer initative ‘, 2022 [Google Scholar]

[pone.0309792.ref010] 10.A, C.E.P.: ‘Delayed presentation and diagnosis of breast cancer in African women: a systematic review’, Annals of Epidemiology, 2017, 27 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref011] 11.S, O.: ‘Prevalence of Themes Linked to Delayed Presentation of Breast Cancer in Africa: AMeta-Analysis of Patient-Reported Studies’, JCO Global Oncol 2020, 6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref012] 12.Richards M., Westcombe A., Love S., Littlejohns P., and Ramirez A.: ‘Influence of delay on survival in patients with breast cancer: a systematic review’, The Lancet, 1999, 353, (9159), pp. 1119–1126 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref013] 13.Robinson E., Mohilever J., and Borovik R.: ‘Factors affecting delay in diagnosis of breast cancer: relationship of delay to stage of disease’, Israel journal of medical sciences, 1986, 22, (5), pp. 333–338 [PubMed] [Google Scholar]

[pone.0309792.ref014] 14.Burgess C., Ramirez A., Richards M., and Love S.: ‘Who and what influences delayed presentation in breast cancer?’, British journal of cancer, 1998, 77, (8), pp. 1343–1348 doi: 10.1038/bjc.1998.224 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref015] 15.Afzelius P., Zedeler K., Sommer H., Mouridsen H.T., and Blichert-Toft M.: ‘Patient’s and doctor’s delay in primary breast cancer: Prognostic implications ’, Acta Oncologica, 1994, 33, (4), pp. 345–351 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref016] 16.Richards M., Smith P., Ramirez A., Fentiman I., and Rubens R.: ‘The influence on survival of delay in the presentation and treatment of symptomatic breast cancer’, British journal of cancer, 1999, 79, (5), pp. 858–864 doi: 10.1038/sj.bjc.6690137 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref017] 17.Macarthur C., and Smith A.: ‘DELAY IN BREAST CANCER AND THE NATURE OF PRESENTING SYMPTOMS’, The Lancet, 1981, 317, (8220), pp. 601–603 doi: 10.1016/s0140-6736(81)92044-4 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref018] 18.Sharma K.: ‘A Systematic Review of Barriers to Breast Cancer Care in Developing Countries Resulting in Delayed Patient Presentation’, Journal of Oncology, 2012 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref019] 19.Alhurishi S.: ‘Factors Influencing Late Presentation for Breast Cancer in the Middle East: A Systematic Review’, Asian Pacific J Cancer Prev, 2011, 12 [PubMed] [Google Scholar]

[pone.0309792.ref020] 20.Agodirin O.: ‘Determinants of Delayed Presentation and Advanced-Stage Diagnosis of Breast Cancer in Africa: A Systematic Review and Meta-Analysis’, Asian Pac J Cancer Prev, 2021, 22 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref021] 21.Petrova D.: ‘Duration of the patient interval in breast cancer and factors associated with longer delays in low‐and middle‐income countries: A systematic review with meta‐analysis’, Psycho‐Oncology, 2022, 32, (13), pp. 24. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref022] 22.Donkor A.: ‘Factors Contributing to Late Presentation of Breast Cancer in Africa: A Systematic Literature Review’, ARCHIVES OF MEDICINE, 2015, 8, (2) [Google Scholar]

[pone.0309792.ref023] 23.Akuoko C.P.: ‘Barriers to early presentation and diagnosis of breast cancer among African women living in sub-Saharan Africa’, PLOS ONE, 2017, 10 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref024] 24.Sobri F.B.: ‘Factors Affecting Delayed Presentation and Diagnosis of Breast Cancer in Asian Developing Countries Women: A Systematic Review’, Asian Pac J Cancer Prev, 2021, 22 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref025] 25.Jones Claire EL: ‘A systematic review of barriers to early presentation and diagnosis with breast cancer among black women’, BMJ OPEN, 2014, 4 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref026] 26.Montazeri A., Ebrahimi M., Mehrdad N., Ansari M., and Sajadian A.: ‘Delayed presentation in breast cancer: a study in Iranian women’, BMC women’s health, 2003, 3, pp. 1–6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref027] 27.Odongo J., Makumbi T., Kalungi S., and Galukande M.: ‘Patient delay factors in women presenting with breast cancer in a low income country’, BMC research notes, 2015, 8, pp. 1–6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref028] 28.Ibrahim N., and Oludara M.: ‘Socio-demographic factors and reasons associated with delay in breast cancer presentation: a study in Nigerian women’, The Breast, 2012, 21, (3), pp. 416–418 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref029] 29.Harirchi I., Ghaemmaghami F., Karbakhsh M., Moghimi R., and Mazaherie H. : ‘Patient delay in women presenting with advanced breast cancer: an Iranian study’, Public health, 2005, 119, (10), pp. 885–891 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref030] 30.Čačala S.R., and Gilart J.: ‘Factors relating to late presentation of patients with breast cancer in Area 2 KwaZulu-Natal, South Africa’, Journal of Global Oncology, 2017, 3, (5), pp. 497–501 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref031] 31.Altwalbeh D., El Dahshan M., and Yassin R.: ‘Factors influencing delayed presentation of breast cancer among Saudi women’, International Journal of Science and Research, 2015, 1, (4), pp. 967–974 [Google Scholar]

[pone.0309792.ref032] 32.Shamsi U., Khan S., Azam I., Usman S., Maqbool A., Gill T., et al.: ‘Patient delay in breast cancer diagnosis in two hospitals in Karachi, Pakistan: preventive and life-saving measures needed’, JCO Global Oncology, 2020, 6, pp. 873–883 doi: 10.1200/GO.20.00034 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref033] 33.Harirchi I., Karbakhsh M., Hadi F., Madani S.S., Sirati F., and Kolahdoozan S.: ‘Patient delay, diagnosis delay and treatment delay for breast cancer: comparison of the pattern between patients in public and private health sectors’, Archives of Breast Cancer, 2015, pp. 52–57 [Google Scholar]

[pone.0309792.ref034] 34.Baig M., Sohail I., Altaf H.N., and Altaf O.S.: ‘Factors influencing delayed presentation of breast cancer at a tertiary care hospital in Pakistan’, Cancer Reports, 2019, 2, (1), pp. e1141. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref035] 35.Stapleton J.M., Mullan P.B., Dey S., Hablas A., Gaafar R., Seifeldin I.A., et al. :Patient‐mediated factors predicting early‐and late‐stage presentation of breast cancer in Egypt’, Psycho‐Oncology, 2011, 20, (5), pp. 532–537 doi: 10.1002/pon.1767 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref036] 36.Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., et al. : ‘The PRISMA 2020 statement: an updated guideline for reporting systematic reviews’, International journal of surgery, 2021, 88, pp. 105906 doi: 10.1016/j.ijsu.2021.105906 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref037] 37.Downes M.J.: ‘Development of a critical appraisal tool to assess the quality of cross-sectional studies (AXIS’, BMJ Open, 2016, 6 doi: 10.1136/bmjopen-2016-011458 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref038] 38.Hassen A.M., Hussien F.M., Asfaw Z.A., and Assen H.E.: ‘Factors associated with delay in breast cancer presentation at the only oncology center in North East Ethiopia: a cross-sectional study’, Journal of multidisciplinary healthcare, 2021, pp. 681–694 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref039] 39.Tesfaw A., Demis S., Munye T., and Ashuro Z.: ‘Patient delay and contributing factors among breast cancer patients at two cancer referral centres in Ethiopia: a cross-sectional study’, Journal of Multidisciplinary Healthcare, 2020, pp. 1391–1401 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref040] 40.Shewarega B., Getachew S., Assefa N., Yesufe A., Trabizsch J., Dandena Y., et al. : ‘Predictors of advanced-stage presentation among breast and cervical cancer patients in Ethiopia’, medRxiv, 2023, pp. 2023.2012. 2016. doi: 10.1074/jbc.M112.435909 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref041] 41.Muhammed J.A., Kroeber E.S., Deribe B., Unverzagt S., Taylor L., Aynalem A., et al.: ‘Prevalence and Factors Associated With Delay in Presentation of Breast Cancer Patients in Ethiopia: A Cross-Sectional Institution-Based Study’, medRxiv, 2022, pp. 2022.2011. 2001.22281792 [Google Scholar]

[pone.0309792.ref042] 42.Gebremariam A., Addissie A., Worku A., Assefa M., Pace L.E., Kantelhardt E.J., et al. : ‘Time intervals experienced between first symptom recognition and pathologic diagnosis of breast cancer in Addis Ababa, Ethiopia: a cross-sectional study’, BMJ open, 2019, 9, (11), pp. e032228. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref043] 43.Abiye M., Assefa A., and Mohammedsani B.: ‘Delay And Contributing Factors In Patients With Breast Cancer At Hiwot Fana Comprehensive Specialized Hospital, Harar, Eastern Ethiopia’, Haramaya University Harar, 2023 [Google Scholar]

[pone.0309792.ref044] 44.Pace L.E., Mpunga T., Hategekimana V., Dusengimana J.-M.V., Habineza H., Bigirimana J.B., et al. : ‘Delays in breast cancer presentation and diagnosis at two rural cancer referral centers in Rwanda’, The oncologist, 2015, 20, (7), pp. 780–788 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref045] 45.Salih A.M., Alfaki M.M., Alam-Elhuda D.M., and Nouradyem M.M.: ‘Factors delaying presentation of Sudanese breast cancer patients: an analysis using Andersen’s model’, Asian Pacific Journal of Cancer Prevention, 2016, 17, (4), pp. 2105–2110 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref046] 46.Egger M., Davey Smith G., Schneider M., and Minder C.: ‘Bias in meta-analysis detected by a simple, graphical test’, BMJ (Clinical research ed.), 1997, 315, (7109), pp. 629–634 doi: 10.1136/bmj.315.7109.629 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref047] 47.Hutajulu S.H., Prabandari Y.S., Bintoro B.S., Wiranata J.A., Widiastuti M., Suryani N.D., et al.: ‘Delays in the presentation and diagnosis of women with breast cancer in Yogyakarta, Indonesia: a retrospective observational study’, PloS one, 2022, 17, (1), pp. e0262468. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref048] 48.Awofeso O., Roberts A.A., Salako O., Balogun L., and Okediji P.: ‘Prevalence and pattern of late-stage presentation in women with breast and cervical cancers in Lagos University Teaching Hospital, Nigeria’, Nigerian Medical Journal, 2018, 59, (6), pp. 74–79 doi: 10.4103/nmj.NMJ_112_17 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref049] 49.Elenwo S.N., Ijah R.F.O.A., and Dimoko A.A.: ‘Factors associated with late presentation of breast cancer in a Teaching Hospital in Port Harcourt, Nigeria’, Nigerian Health Journal, 2022, 22, (1), pp. 140–152 [Google Scholar]

[pone.0309792.ref050] 50.Thakur N., Humne A., and Godale L.: ‘Delay in presentation to the hospital and factors affecting it in breast cancer patients attending tertiary care center in Central India’, Indian journal of cancer, 2015, 52, (1), pp. 102–105 [DOI] [PubMed] [Google Scholar]

[pone.0309792.ref051] 51.Abdulkareem A.A., Ghalib H.A., and Rashaan M.I.: ‘Factors Causing Delayed Presentations of Breast Cancer among Female patients in Sulaimaniyah Governorate, Iraq’, 2023 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref052] 52.Khan M.A., Hanif S., Iqbal S., Shahzad M.F., Shafique S., and Khan M.T.: ‘Presentation delay in breast cancer patients and its association with sociodemographic factors in North Pakistan’, Chinese Journal of Cancer Research, 2015, 27, (3), pp. 288. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref053] 53.Gbenonsi G., Boucham M., Belrhiti Z., Nejjari C., Huybrechts I., and Khalis M.: ‘Health System Factors That Influence Treatment Delay in Women With Breast Cancer in Sub-saharan Africa: A Systematic Review ’, 2021 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref054] 54.Gbenonsi G., Boucham M., Belrhiti Z., Nejjari C., Huybrechts I., and Khalis M.: ‘Health system factors that influence diagnostic and treatment intervals in women with breast cancer in sub-Saharan Africa: a systematic review’, BMC Public Health, 2021, 21, pp. 1–20 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref055] 55.Simon A.E., Waller J., Robb K., and Wardle J.: ‘Patient delay in presentation of possible cancer symptoms: the contribution of knowledge and attitudes in a population sample from the United Kingdom’, Cancer Epidemiology, Biomarkers & Prevention, 2010, 19, (9), pp. 2272–2277 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref056] 56.Innos K., Padrik P., Valvere V., Eelma E., Kütner R., Lehtsaar J., et al. : ‘Identifying women at risk for delayed presentation of breast cancer: a cross-sectional study in Estonia’, BMC Public Health, 2013, 13, pp. 1–7 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref057] 57.Gulzar F., Akhtar M.S., Sadiq R., Bashir S., Jamil S., and Baig S.M.: ‘Identifying the reasons for delayed presentation of Pakistani breast cancer patients at a tertiary care hospital’, Cancer management and research, 2019, pp. 1087–1096 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref058] 58.Macleod U.: ‘Risk factors for delayed presentation and referral of symptomatic cancer: evidence for common cancers’, British Journal of Cancer, 2019, 19. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref059] 59.Nosarti C.: ‘ Delay in presentation symptomatic referals to breast clinic:patient and system factors’, British Journal of Cancer (2015, 82, (3) [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref060] 60.Al-Shiekh S.S.A.: ‘Factors affecting delay in the presentation of breast cancer symptoms among women in Gaza, occupied Palestinian territory: a cross-sectional survey’, BMJopen, 2022, 12 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0309792.ref061] 61.Black E.: ‘Improving early detection of breast cancer in sub-Saharan Africa: why mammography may not be the way forward’, Black and Richmond Globalization and Health 2019, 15, (3) [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Delayed presentation of breast cancer patients and contributing factors in East Africa: Systematic review and meta-analysis

Chalie Mulugeta

Tadele Emagneneh

Getinet Kumie

Betelhem Ejigu

Abebaw Alamrew

Roles

Abstract

Introduction

Methods

Results

Conclusion

Introduction

Methods and materials

Study protocol and reporting

Inclusion criteria

Table 1. Show the inclusion and exclusion criteria.

Exclusion criteria

Variable measure

Search strategy

Data extraction

Quality assessment/critical appraisal

Result

Fig 1. PRISMA flowchart diagram of the study selection process.

Study characteristics

Table 2. Description of included articles delayed presentation of breast cancer and associated factors in East Africa.

Pooled prevalence of delayed patient presentation of breast cancer in East Africa

Fig 2. Pooled prevalence late presentation of breast cancer patient in East Africa 2024.

Subgroup analysis

Fig 3. Subgroup analysis of pooled prevalence late presentation of breast cancer patient in East Africa 2024.

Publication bias

Fig 4. Funnel plot publication bias plot for the prevalence of late presentation of breast cancer patient in East Africa.

Sensitivity analysis

Table 3. Shows a sensitivity analysis of delayed presentation of breast cancer patients in east Africa.

Factors associated with delay presentation of breast cancer patient in East Africa

Table 4. Factors associated with delayed presentation of breast cancer patients in east Africa.

Age of participant

Fig 5. Pooled odds ratio for the association between age with delay presentation of breast cancer patient in East Africa.

Educational status

Fig 6. Pooled odds ratio for the association between educational status with delay presentation of breast cancer patient in East Africa.

Residence

Fig 7. Pooled odds ratio for the association between rural residences with delay presentation of breast cancer participants in East Africa.

Absence of breast pain

Fig 8. Pooled odds ratio for the association between not having breast pain with delay presentation of breast cancer participants in East Africa.

Distance from health facility

Fig 9. Pooled odds ratio for the association between >5km away from health facility with delay presentation of breast cancer participants in East Africa.

Visit traditional healer

Fig 10. Pooled odds ratio for the association between visit traditional healer with delay presentation of breast cancer in East Africa.

Factors not associated with delayed presentation of a breast cancer patient in East Africa

Employee

Fig 11. Pooled odds ratio for the association between employed with delay presentation of breast cancer in East Africa.

Marital status

Fig 12. Pooled odds ratio for the association between married with delay presentation of breast cancer in East Africa.

Not having awareness of breast cancer

Fig 13. Pooled odds ratio for the association between no awareness of breast cancer with delay presentation of breast cancer in East Africa.

Not having lump under armpit

Fig 14. Pooled odds ratio for the association between no lump underarmpit with delay presentation of breast cancer in East Africa.

Have no family history of breast cancer

Fig 15. Pooled odds ratio for the association between have no family history of breast cancer with delay presentation of breast cancer in East Africa.

Discussion

Strength of the study

Limitations of the study

Conclusion

Supporting information

Acknowledgments

Data Availability

Funding Statement

References

Decision Letter 0

Wenjie Shi

Roles

Author response to Decision Letter 0

Decision Letter 1

Wenjie Shi

Roles

Author response to Decision Letter 1

Decision Letter 2

Wenjie Shi

Roles