Global variations in lung cancer incidence by histological subtype in 2020: a population-based study.

BACKGROUND: Lung cancer is the second most common cancer worldwide, yet the distribution by histological subtype remains unknown. We aimed to quantify the global, regional, and national burden of lung cancer incidence for the four main subtypes in 185 countries and territories. METHODS: In this population-based study, we used data from Cancer Incidence in Five Continents Volume XI and the African Cancer Registry Network to assess the proportions of adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma among all lung cancers by country, sex, and age group and subsequently applied these data to corresponding national (GLOBOCAN) estimates of lung cancer incidence in 2020. Unspecified morphologies were reallocated to specified subtypes. Age-standardised incidence rates were calculated using the world standard population to compare subtype risks worldwide, adjusted for differences in age composition between populations by country. FINDINGS: In 2020, there were an estimated 2 206 771 new cases of lung cancer, with 1 435 943 in males and 770 828 in females worldwide. In males, 560 108 (39%) of all lung cancer cases were adenocarcinoma, 351 807 (25%) were squamous cell carcinoma, 163 862 (11%) were small-cell carcinoma, and 115 322 (8%) were large-cell carcinoma cases. In females, 440 510 (57%) of all lung cancer cases were adenocarcinoma, 91 070 (12%) were squamous cell carcinoma, 68 224 (9%) were small-cell carcinoma, and 49 246 (6%) were large-cell carcinoma cases. Age-standardised incidence rates for adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma, respectively, were estimated to be 12·4, 7·7, 3·6, and 2·6 per 100 000 person-years in males and 8·3, 1·6, 1·3, and 0·9 per 100 000 person-years in females worldwide. The incidence rates of adenocarcinoma exceeded those of squamous cell carcinoma in 150 of 185 countries in males and in all 185 countries in females. The highest age-standardised incidence rates per 100 000 person-years for adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma, respectively, for males occurred in eastern Asia (23·5), central and eastern Europe (17·5), western Asia (7·2), and south-eastern Asia (11·0); and for females occurred in eastern Asia (16·0), northern America (5·4), northern America (4·7), and south-eastern Asia (3·4). The incidence of each subtype showed a clear gradient according to the Human Development Index for male and female individuals, with increased rates in high and very high Human Development Index countries. INTERPRETATION: Adenocarcinoma has become the most common subtype of lung cancer globally in 2020, with incidence rates in males exceeding those of squamous cell carcinoma in most countries, and in females in all countries. Our findings provide new insights into the nature of the global lung cancer burden and facilitates tailored national preventive actions within each world region. FUNDING: None.

Lack of Association of C677T Methylenetetrahydrofolate Reductase Polymorphism with Breast Cancer Risk in Mali.

Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, and 0.8% for TT. Healthy controls showed a similar distribution with 90.6% for CC, 8.8% for CT, and 0.6% for TT. We found no statistical association between the C677T polymorphism and breast cancer risk for the codominant models CT and TT (p > 0.05). The same trend was observed when the analysis was extended to other genetic models, including dominant (p = 0.50), recessive (p = 0.87), and additive (p = 0.50) models. The C677T polymorphism of MTHFR gene did not influence the risk of breast cancer in the Malian samples.

Trends in the incidence of ovarian cancer in sub-Saharan Africa.

Ovarian cancer (OC) is one of the commonest cancers of women in sub-Saharan Africa (SSA), although to date no data have been available on time trends in incidence to better understand the disease pattern in the region. We estimate time trends by histological subtype from 12 population-based cancer registries in 11 countries: Kenya (Nairobi), Mauritius, Seychelles, Uganda (Kampala), Congo (Brazzaville), Zimbabwe (Bulawayo and Harare), Cote d'Ivoire (Abidjan), The Gambia, Mali (Bamako), Nigeria (Ibadan) and South Africa (Eastern Cape). The selected registries were those that could provide consistent estimates of the incidence of ovarian cancer and with quality assessment for periods of 10 or more years. A total of 5423 cases of OC were included. Incidence rates have been increasing in all registries except Brazzaville, Congo, where a nonsignificant decline of 1% per year was seen. Statistically significant average annual increases were seen in Mauritius (2.5%), Bamako (5.3%), Ibadan (3.9%) and Eastern Cape (8%). Epithelial ovarian cancer was responsible for the increases observed in all registries. Statistically significant average annual percentage changes (AAPC) for epithelial OC were present in Bamako (AAPC = 5.9%), Ibadan (AAPC = 4.7%) and Eastern Cape (AAPC = 11.0%). Creating awareness among professionals of the growing importance of the disease is surely an important step to improving availability of, and access to, diagnosis and treatment of OC in SSA. Support must be given to the cancer registries to improve the availability of good-quality data on this important cancer.

Decrease in liver cancer incidence rates in Bamako, Mali over 28 years of population-based cancer registration (1987-2015).

BACKGROUND: Primary liver cancer is common in West Africa due to endemic risk factors. However, epidemiological studies of the global burden and trends of liver cancer are limited. We report changes in trends of the incidence of liver cancer over a period of 28 years using the population-based cancer registry of Bamako, Mali. AIM: To assess the trends and patterns of liver cancer by gender and age groups by analyzing the cancer registration data accumulated over 28 years (1987-2015) of activity of the population-based registry of the Bamako district. METHODS: Data obtained since the inception of the registry in 1987 through 2015 were stratified into three periods (1987-1996, 1997-2006, and 2007-2015). Age-standardized rates were estimated by direct standardization using the world population. Incidence rate ratios and the corresponding 95% confidence intervals (CI) were estimated using the early period as the reference (1987-1996). Joinpoint regression models were used to assess the annual percentage change and highlight trends over the entire period (from 1987 to 2015). RESULTS: Among males, the age-standardized incidence rates significantly decreased from 19.41 (1987-1996) to 13.12 (1997-2006) to 8.15 (2007-2015) per 105 person-years. The incidence rate ratio over 28 years was 0.42 (95%CI: 0.34-0.50), and the annual percentage change was -4.59 [95%CI: (-6.4)-(-2.7)]. Among females, rates dropped continuously from 7.02 (1987-1996) to 2.57 (2007-2015) per 105 person-years, with an incidence rate ratio of 0.37 (95%CI: 0.28-0.45) and an annual percentage change of -5.63 [95%CI: (-8.9)-(-2.3)]. CONCLUSION: The population-based registration showed that the incidence of primary liver cancer has steadily decreased in the Bamako district over 28 years. This trend does not appear to result from biases or changes in registration practices. This is the first report of such a decrease in an area of high incidence of liver cancer in Africa. This decrease may be explained by the changes and diversity of diet that could reduce exposure to aflatoxins through dietary contamination in this population.

Association of the Interleukin-10-592C/A Polymorphism and Cervical Cancer Risk: A Meta-Analysis.

A literature review showed some discrepancies regarding the association of -592C/A with the risk of cervical cancer. To allow more precise analysis of the data by increasing the number of cases studied and more acceptable generalization by considering results from different sources, the present meta-analysis was performed on available published studies that explored the relationship between SNP-592C/A of the IL-10 gene and the risk of cervical cancer. Eleven available studies, including 4187 cases and 3311 controls, were included in this study investigating the relationship between the -592C/A polymorphism of IL-10 and cervical cancer risk. Fixed-effects or random-effects models were performed with pooled odds ratios (ORs). Heterogeneity and bias tests were performed by the inconsistency test and funnel plot, respectively. The overall analysis showed an increased susceptibility to cervical cancer with the -592C/A polymorphism of the IL-10 gene for the recessive model (OR = 1.30, 95% CI = 1.14-1.49), dominant model (OR = 1.36, 95% CI = 1.09-1.70), and additive model (OR = 1.25, 95% CI = 1.09-1.44). Regarding ethnicity, a significant association of the -592C/A polymorphism of the IL-10 gene was linked to an elevated risk of cervical cancer for all genetic models (recessive, dominant, and additive) in the Asian populations and for the recessive and additive models in Caucasians with P < 0.05. The -592C/A polymorphism of the IL-10 gene may be considered a risk factor for cervical cancer.

Influence of CYP2B6 and CYP3A4 polymorphisms on the virologic and immunologic responses of patients treated with efavirenz-containing regimen.

OBJECTIVES: The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polymorphisms on the virological and immunologic responses of HIV patients. A total of 153 HIV-positive patients were enlisted for the study. PATIENTS AND METHODS: Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Samples were identified using TaqMan genotyping assays. RESULTS: The AG in CYP2B6 rs2279343 was associated with VLS compared to homozygous AA. In the dominant model, the AG/GG genotypes were associated with VLS compared to the AA genotype. Moreover, in overdominant model, the AG genotype was associated with VLS compared to AA/GG. Regarding immunological response, only the AG in SNP rs2279343 CYP2B6 was associated with an increase in CD4 cell count between baseline and M6. In CYP2B6 rs3745274, the CD4 cell count at M6 was higher than that of baseline for GG carriers and for GT carriers. In CYP3A4 rs2740574, the TC carriers showed a higher median CD4 count at M6 compared to that of the baseline count, as well as for CC carriers. The best genotypes combination associated with CD4 cell count improvement were AA/AG in SNP rs2279343 and GG/GT in SNP rs3745274. CONCLUSION: Our findings support the fact that CYP2B6 rs2279343 could help in the prediction of VLS and both SNPs rs3745274 and rs2279343 in CYP2B6 and CYP3A4 rs2740574 were associated with immune recovery in Malian HIV-positive patients.

Relationships between gut microbiota, red meat consumption and colorectal cancer.

Excessive consumption of red and processed meat has been associated with a higher risk of developing colorectal cancer. There are many attempts to explain the risk of colorectal cancer associated with the consumption of red and processed meat: The temperature cooking of meat such as grilling and smoking contribute to the formation of mutagenic compounds including heterocyclic amines and polycyclic aromatic hydrocarbons.Heme iron in red meat is involved in the formation of N-nitroso compounds and lipid peroxidation products in the digestive tract.Fatty red meat is involved in the production of secondary bile acids by the bacteria of the gut microbiota. Many of the products formed are genotoxic and can cause DNA damage and initiate carcinogenesis of colorectal cancer. Various mechanisms contributing to their genotoxic role have been established in human and animal studies. In addition, there is increasing evidence that compounds formed from red and processed meat interact with the gut microbiota in colorectal cancer pathways. Although several early studies in animals and humans suggest a direct causal role of the gut microbiota in the development of colorectal cancer, the links between diet, gut microbiota, and colonic carcinogenesis are largely associations rather than proven causal relationships. Various biological mechanisms, including inflammation and oxidative stress can lead to DNA damage, gut dysbiosis, and therefore increase the risk of colorectal cancer. Dysbiosis of the gut microbiota may increase the risk of colorectal cancer through dietary component promotion of colonic carcinogenesis. In this paper, we review and update current knowledge about the relationships between red meat consumption, gut microbiota, and colorectal cancer.

[Contribution of CT scan and radio-histological concordance in the diagnosis of maxillomandibular tumors at the Dental University Hospital of BAMAKO]. / Apport de la tomodensitometrie et concordance radio-histologique dans le diagnostic des tumeurs maxillo-mandibulaires au Centre Hospitalier Universitaire-Centre National D'Odonto-Stomatologie (CHU-CNOS) de BAMAKO.

INTRODUCTION: The aim of this study was to investigate the contribution of computed tomography (CT) and its degree of concordance with pathological examination in the etiological diagnosis of maxillomandibulartumours. MATERIALS AND METHODS: Our study was cross-sectional, retrospective and prospective. It took place over a period of five years and six months and included cases of maxilla-mandibulartumours confirmed by pathological examination after clinical examination and CT scan. Data were collected from medical records, entered and analysed with SPSS 21.0 software. RESULTS: Men represented 55.7% of cases with a sex ratio of 1.25. The duration of symptoms on presentation varied from 1 month to 27 years (mean 24.37+/- 48 months). This consultation was motivated in 92.6% of cases by a mandibular swelling. Squamous cell carcinomas were the most common on pathological examination with 34.2% of cases followed by ameloblastomas in 24.2% of cases. There was good agreement between the results of the CT scan and those of the pathological examination (Cohen's Kappa=0.77). CONCLUSION: CT remains a reliable tool in the diagnosis of maxillomandibulartumours.

INTRODUCTION: L'objectif de cette étude était, d'étudier l'apport de la tomodensitométrie (TDM) et son degréde concordance avec l'examen anatomo-pathologique dans le diagnostic étiologique des tumeurs maxillo-mandibulaires. MATÉRIELS ET MÉTHODES: Notre étude était transversale, rétrospective et prospective. Elle s'est déroulée sur une période de cinq ans et six mois et portait sur les cas de tumeurs maxillo-mandibulaires confirmés par l'examen anatomopathologique après un examen clinique et la réalisation d'une tomodensitométrie. Les données ont été recueillies à partir des dossiers médicaux, saisies et analysées avec le logiciel SPSS 21.0. RÉSULTATS: les hommes représentaient 55,7% des cas avec un sex-ratio de 1,25. Le délai de consultation variait de1 mois à 27 ans (moyenne 24,37+/- 48 mois).Cette consultation était motivée dans 92,6% des cas par une tuméfaction mandibulaire. Lescarcinomes épidermoïdes ont été les plus retrouvés à l'examen anatomopathologique avec 34,2 % des cas suivis des améloblastomes dans 24,2% des cas. Il existait une bonne concordance entre les résultats de latomodensitométrie etceux de l'examen anatomopathologique(Kappa de Cohen=0,77). CONCLUSION: la tomodensitométrie reste un outil fiable dans le diagnostic des tumeurs maxillo-mandibulaires.

Breast Cancer Diagnostics, Therapy, and Outcomes in Sub-Saharan Africa: A Population-Based Registry Study.

BACKGROUND: Breast cancer (BC) is the most common cancer in sub-Saharan Africa (SSA). However, little is known about the actual therapy received by women with BC and their survival outcome at the population level in SSA. This study aims to describe the cancer-directed therapy received by patients with BC at the population level in SSA, compare these results with the NCCN Harmonized Guidelines for SSA (NCCN Harmonized Guidelines), and evaluate the impact on survival. METHODS: Random samples of patients with BC (≥40 patients per registry), diagnosed from 2009 through 2015, were drawn from 11 urban population-based cancer registries from 10 countries (Benin, Congo, Cote d'Ivoire, Ethiopia, Kenya, Mali, Mozambique, Namibia, Uganda, and Zimbabwe). Active methods were used to update the therapy and outcome data of diagnosed patients ("traced patients"). Excess hazards of death by therapy use were modeled in a relative survival context. RESULTS: A total of 809 patients were included. Additional information was traced for 517 patients (63.8%), and this proportion varied by registry. One in 5 traced patients met the minimum diagnostic criteria (cancer stage and hormone receptor status known) for use of the NCCN Harmonized Guidelines. The hormone receptor status was unknown for 72.5% of patients. Of the traced patients with stage I-III BC (n=320), 50.9% received inadequate or no cancer-directed therapy. Access to therapy differed by registry area. Initiation of adequate therapy and early-stage diagnosis were the most important determinants of survival. CONCLUSIONS: Downstaging BC and improving access to diagnostics and care are necessary steps to increase guideline adherence and improve survival for women in SSA. It will also be important to strengthen health systems and facilities for data management in SSA to facilitate patient follow-up and disease surveillance.

[Treatment of cancer pain in Mali: Experience of the mother-child medical oncology service of the CHU in Bamako]. / Prise en charge de la douleur cancéreuse au Mali : expérience du service mère­enfant d'oncologie médicale du CHU de Bamako.

Two hundred patients were refereed for advanced cancer to the oncology department of Luxembourg Hospital in Bamako. All these patients reported intense pain (88 %) which was only treated before admission by OMS level 1 analgesics. It clearly shows that cancer pain is undertreated in Malian peripheral sanitary structures. After evaluation of the pain by analog visual and verbal scales patients, the appropriate analgesic drugs such as morphine (OMS level 3) were given. A control of the pain was obtained in all the patients (100 %) with a dramatic improvement in quality of life. This study emphasizes the need for a pain control program at the Malian state level with a basic education of care givers, hospital-centric networks and access to morphine and opioids at the different levels involved in cancer management.

Distribution of alleles, genotypes and haplotypes of the CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) genes in the Malian population: Implication for pharmacogenetics.

ABSTRACT: Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide range of compounds, including xenobiotics, drugs, hormones and vitamins. It is noteworthy that these enzymes are highly polymorphic and, depending on the genetic makeup, an individual may have impaired enzymatic activity. Therefore, the identification of genetic variants in these genes could facilitate the implementation of pharmacogenetic studies and genetic predisposition to multifactorial diseases. We have established the frequencies of CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) alleles and genotypes in 209 healthy Malian subjects using TaqMan drug metabolism genotyping assays for allelic discrimination. Allele frequencies were 37% for CYP2B6 rs3745274; 38% for CYP2B6 rs2279343; and 75% for CYP3A4 rs2740574 respectively. Overall, the frequencies observed in Mali are statistically comparable to those reported across Africa except North Africa. The major haplotypes in CYP2B6 rs3745274 and CYP2B6 rs2279343 were represented by GA (60.24%) followed by TG (35.36%). We noted a strong linkage disequilibrium between CYP2B6 rs3745274 and CYP2B6 rs2279343 with D' = 0.91 and r2 = 0.9. The frequencies of the genotypic combinations were 43.5% (GT/AG), 37.3% (GG/AA) and 11.5% (TT/GG) in the combination of CYP2B6-rs3745274 and CYP2B6-rs2279343; 26.8% (GT/CC), 25.4%, (GT/CT), 17.2% and GG/CT in the combination CYP2B6-rs3745274-CYP3A4-rs2740574; 26.8% (AG/CC), 23.9% (AA/CC), 19.1% (AG/CT), and 11% (AA/CT) in the combination CYP2B6-rs2279343-CYP3A4-rs2740574, respectively. The most common triple genotype was GT/AG/CC with 24.9%, followed by GG/AA/CC with 23.9%, GT/AG/CT with 16.7%, and GG/AA/CT with 10%. Our results provide new insights into the distribution of these pharmacogenetically relevant genes in the Malian population. Moreover, these data will be useful for studies of individual genetic variability to drugs and genetic predisposition to diseases.

Rising Prostate Cancer Incidence in Sub-Saharan Africa: A Trend Analysis of Data from the African Cancer Registry Network.

BACKGROUND: Prostate cancer is the leading cancer in men in sub-Saharan Africa (SSA) regarding incidence and mortality. Published data from a few registries in SSA suggest that the rates are still rising, but there is little comprehensive information on the time trends of prostate cancer incidence. METHODS: We analyzed registry data on 13,170 incident prostate cancer cases in men aged 40 years or above, from 12 population-based cancer registries in 11 SSA countries, with at least a 10-year time span of comparable data. RESULTS: We observed an increase in cumulative risks (CR) and age-standardized incidence rates (ASR) over time in all registries (statistically significant in all but one). The highest values of CR were found in Seychelles and Harare (Zimbabwe). The highest annual increase in the ASRs was seen in Seychelles and Eastern Cape (South Africa), whereas the lowest was seen in Mauritius. We mainly found a steady increase in incidence with age and during successive periods. CONCLUSIONS: This analysis reveals that prostate cancer incidence rates are rising in many populations in SSA-often very rapidly-which is in contrast to recent observations worldwide. We acknowledge that the reasons are multifactorial and largely remain unclear, but believe that they are primarily associated with improvements in health care systems, for example, a broader use of prostate-specific antigen testing. IMPACT: This study is the first to compare population-level data on time trends of prostate cancer incidence between multiple countries of SSA, presenting the different rates of increase in 11 of them.

p.Arg72Pro polymorphism of P53 and breast cancer risk: a meta-analysis of case-control studies.

BACKGROUND: The effect of the p.Arg72Pro variant of the P53 gene on the risk of development ofbreast cancer remains variable in populations. However, the use ofstrategies such aspoolingage-matched controls with disease may provide a consistent meta-analysis. Our goal was to perform a meta-analysis in order to assess the association of p.Arg72Pro variant of P53 gene with the risk of breast cancer. METHODS: Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Case-control studies with age-matched on breast cancer havingevaluated the genotype frequencies of the TP53 p.Arg72Pro polymorphism were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. RESULTS: Twenty-one publications with 7841 cases and 8876 controls were evaluated in this meta-analysis. Overall, our results suggested that TP53 p.Arg72Pro was associated with the risk of breast cancer for the dominant model (OR = 1.09, 95% CI = 1.02-1.16, P = 0.01) and the additive model (OR = 1.09, 95% CI = 1.01-1.17, P = 0.03), but not for the recessive model (OR = 1.07, 95% CI = 0.97-1.18, P = 0.19). According to the ethnic group analysis, Pro allele was associated with the risk of breast cancer in Caucasians for the dominant model and additive model (P = 0.02), and Africans for the recessive model and additive model (P = 0.03). CONCLUSIONS: This meta-analysis found a significant association between TP53 p.Arg72Pro polymorphism and the risk of breast cancer. Individuals carrying at least one Pro allele were more likely to have breast cancer than individuals harboring the Arg allele.

Prevalence and determinants of breast cancer screening in four sub-Saharan African countries: a population-based study.

OBJECTIVES: Breast cancer is the most prevalent cancer and the second leading cause of cancer-related deaths among women after cervical cancer in much of sub-Saharan Africa. This study aims to examine the prevalence and sociodemographic-socioeconomic factors associated with breast cancer screening among women of reproductive age in sub-Saharan Africa. DESIGN: A weighted population-based cross-sectional study using Demographic and Health Surveys (DHS) data. We used all available data on breast cancer screening from the DHS for four sub-Saharan African countries (Burkina Faso, Ivory Coast, Kenya and Namibia). Breast cancer screening was the outcome of interest for this study. Multivariable Poisson regression was used to identify independent factors associated with breast cancer screening. SETTING: Four countries participating in the DHS from 2010 to 2014 with data on breast cancer screening. PARTICIPANTS: Women of reproductive age 15-49 years (N=39 646). RESULTS: The overall prevalence of breast cancer screening was only 12.9% during the study period, ranging from 5.2% in Ivory Coast to 23.1% in Namibia. Factors associated with breast cancer screening were secondary/higher education with adjusted prevalence ratio (adjusted PR)=2.33 (95% CI: 2.05 to 2.66) compared with no education; older participants, 35-49 years (adjusted PR=1.73, 95% CI : 1.56 to 1.91) compared with younger participants 15-24 years; health insurance coverage (adjusted PR=1.57, 95% CI: 1.47 to 1.68) compared with those with no health insurance and highest socioeconomic status (adjusted PR=1.33, 95% CI : 1.19 to 1.49) compared with lowest socioeconomic status. CONCLUSION: Despite high breast cancer mortality rates in sub-Saharan Africa, the prevalence of breast cancer screening is substantially low and varies gradually across countries and in relation to factors such as education, age, health insurance coverage and household wealth index level. These results highlight the need for increased efforts to improve the uptake of breast cancer screening in sub-Saharan Africa.

Breast cancer pathology services in sub-Saharan Africa: a survey within population-based cancer registries.

BACKGROUND: Pathologists face major challenges in breast cancer diagnostics in sub-Saharan Africa (SSA). The major problems identified as impairing the quality of pathology reports are shortcomings of equipment, organization and insufficiently qualified personnel. In addition, in the context of breast cancer, immunohistochemistry (IHC) needs to be available for the evaluation of biomarkers. In the study presented, we aim to describe the current state of breast cancer pathology in order to highlight the unmet needs. METHODS: We obtained information on breast cancer pathology services within population-based cancer registries in SSA. A survey of 20 participating pathology centres was carried out. These centres represent large, rather well-equipped pathologies. The data obtained were related to the known population and breast cancer incidence of the registry areas. RESULTS: The responding pathologists served populations of between 30,000 and 1.8 million and the centres surveyed dealt with 10-386 breast cancer cases per year. Time to fixation and formalin fixation time varied from overnight to more than 72 h. Only five centres processed core needle biopsies as a daily routine. Technical problems were common, with 14 centres reporting temporary power outages and 18 centres claiming to own faulty equipment with no access to technical support. Only half of the centres carried out IHC in their own laboratory. For three centres, IHC was only accessible outside of the country and one centre could not obtain any IHC results. A tumour board was established in 13 centres. CONCLUSIONS: We conclude that breast cancer pathology services ensuring state-of-the-art therapy are only available in a small fraction of centres in SSA. To overcome these limitations, many of the centres require larger numbers of experienced pathologists and technical staff. Furthermore, equipment maintenance, standardization of processing guidelines and establishment of an IHC service are needed to comply with international standards of breast cancer pathology.

Association of PIN3 16-bp duplication polymorphism of TP53 with breast cancer risk in Mali and a meta-analysis.

BACKGROUND: Breast cancer, the most common tumor in women in Mali and worldwide has been linked to several risk factors, including genetic factors, such as the PIN3 16-bp duplication polymorphism of TP53. The aim of our study was to evaluate the role of the PIN3 16-bp duplication polymorphism in the susceptibility to breast cancer in the Malian population and to perform a meta-analysis to better understand the correlation with data from other populations. METHODS: We analyzed the PIN3 16-bp duplication polymorphism in blood samples of 60 Malian women with breast cancer and 60 healthy Malian women using PCR. In addition, we performed a meta-analysis of case-control study data from international databases, including Pubmed, Harvard University Library, Genetics Medical Literature Database, Genesis Library and Web of Science. Overall, odds ratio (OR) with 95% CI from fixed and random effects models were determined. Inconsistency was used to assess heterogeneity between studies and publication bias was estimated using the funnel plot. RESULTS: In the studied Malian patients, a significant association of PIN3 16-bp duplication polymorphism with breast cancer risk was observed in dominant (A1A2 + A2A2 vs. A1A1: OR = 2.26, CI 95% = 1.08-4.73; P = 0.02) and additive (A2 vs. A1: OR = 1.87, CI 95% = 1.05-3.33; P = 0.03) models, but not in the recessive model (P = 0.38). In the meta-analysis, nineteen (19) articles were included with a total of 6018 disease cases and 4456 controls. Except for the dominant model (P = 0.15), an increased risk of breast cancer was detected with the recessive (OR = 1.46, 95% CI = 1.15-1.85; P = 0.002) and additive (OR = 1.11, 95% CI = 1.02-1.19; P = 0.01) models. CONCLUSION: The case-control study showed that PIN3 16-bp duplication polymorphism of TP53 is a significant risk factor for breast cancer in Malian women. These findings are supported by data from the meta-analysis carried out on different ethnic groups around the world.

Breast cancer survival in sub-Saharan Africa by age, stage at diagnosis and human development index: A population-based registry study.

Breast cancer is the leading cancer diagnosis and second most common cause of cancer deaths in sub-Saharan Africa (SSA). Yet, there are few population-level survival data from Africa and none on the survival differences by stage at diagnosis. Here, we estimate breast cancer survival within SSA by area, stage and country-level human development index (HDI). We obtained data on a random sample of 2,588 breast cancer incident cases, diagnosed in 2008-2015 from 14 population-based cancer registries in 12 countries (Benin, Cote d'Ivoire, Ethiopia, Kenya, Mali, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Uganda and Zimbabwe) through the African Cancer Registry Network. Of these, 2,311 were included for survival analyses. The 1-, 3- and 5-year observed and relative survival (RS) were estimated by registry, stage and country-level HDI. We equally estimated the excess hazards adjusting for potential confounders. Among patients with known stage, 64.9% were diagnosed in late stages, with 18.4% being metastatic at diagnosis. The RS varied by registry, ranging from 21.6%(8.2-39.8) at Year 3 in Bulawayo to 84.5% (70.6-93.5) in Namibia. Patients diagnosed at early stages had a 3-year RS of 78% (71.6-83.3) in contrast to 40.3% (34.9-45.7) at advanced stages (III and IV). The overall RS at Year 1 was 86.1% (84.4-87.6), 65.8% (63.5-68.1) at Year 3 and 59.0% (56.3-61.6) at Year 5. Age at diagnosis was not independently associated with increased mortality risk after adjusting for the effect of stage and country-level HDI. In conclusion, downstaging breast cancer at diagnosis and improving access to quality care could be pivotal in improving breast cancer survival outcomes in Africa.

Health system organisation and patient pathways: breast care patients' trajectories and medical doctors' practice in Mali.

BACKGROUND: Information on pathways of women seeking diagnostic services due to breast- related symptoms can help highlight challenges related to the healthcare system in improving early diagnosis of breast cancer. METHODS: We retrospectively analysed the entire patient pathway, from first symptom recognition via initial healthcare visit up to final diagnosis at the pathology service in Mali. Data from questionnaire-based structured patient interviews (n = 124) were used to calculate time to first healthcare visit (median 91 days) and consecutive time to diagnosis (median 21 days) and to extract information on type of initially visited healthcare facility (community healthcare centre, referral hospital, tertiary hospital, private clinic). Median time to first healthcare visit and time to diagnosis and type of initially-visited healthcare facility were cross-tabulated with patient characteristics. An additional survey among (n = 30) medical doctors in the community healthcare centres and referral hospitals in Bamako was conducted to understand current knowledge and referral practice with respect to female patients with breast-related symptoms. RESULTS: Patients who initially visited private clinics had the shortest time to first healthcare visit (median 44 days), but the longest time to diagnosis (median 170 days). Patients visiting community healthcare centres and referral hospitals took longest for a first healthcare visit (median 153 and 206 days, respectively), but the time to diagnosis was shorter (median 95 and 7 days, respectively). The majority of patients (45%) initially visited a tertiary hospital; these patients had shortest total time to diagnosis (median 56 days health seeking and 8 days diagnostic time), but did not follow the recommended pathway for patients in the pyramidal healthcare system in Mali. The doctors' survey showed lower breast cancer knowledge in the community healthcare centres than in the referral hospitals. However, most doctors felt able to recognise suspected cases of cancer and referred patients directly to a hospital. CONCLUSIONS: The role of different healthcare facilities in ensuring triage of patients with breast-related symptoms needs to be defined before any early detection initiatives are implemented. Especially at the entry level of the healthcare system, the access and quality of health services need to be strengthened.

Factors associated with time to first healthcare visit, diagnosis and treatment, and their impact on survival among breast cancer patients in Mali.

OBJECTIVE: To analyse patient and healthcare system related factors influencing the time to first healthcare visit, diagnosis and treatment of breast cancer patients in sub-Saharan Africa and the impact on survival in order to advise on early detection strategies. METHODS: A prospective hospital cohort study was conducted at the only pathology department in Mali, at the University Hospital in Bamako. All the female patients with a breast cancer diagnosis between January and April 2016 were interviewed with a structured questionnaire (N = 64) to gather information about breast symptom recognition and first healthcare visit. Information on beginning of treatment and survival were collected at 18-months follow-up. Simple Cox regression analyses were performed. RESULTS: The median time to first healthcare visit was 4.8 months, from first healthcare visit to diagnosis was 0.9 months and for the patients who started treatment (N = 46) the time from diagnosis to treatment was 1.3 months. Knowledge of breast-self-examination and correct symptom interpretation increased the chance of an earlier healthcare visit. Prolonged time to diagnosis was found with shorter duration to first healthcare visit, for working women compared to housewives and for those living within Bamako. Living outside Bamako and smaller tumour size (T1/T2) prolonged time to treatment. Visit of a traditional healer and larger tumour size (T3/T4) shortened survival time, whereas time to first healthcare visit and subsequent time to diagnosis had no influence on survival. CONCLUSIONS: Down-staging strategies are only useful if the continuum of breast cancer care is warranted for the majority of patients.

Why Do Women with Breast Cancer Get Diagnosed and Treated Late in Sub-Saharan Africa? Perspectives from Women and Patients in Bamako, Mali.

BACKGROUND: Breast cancer, the most common cancer among women worldwide, has a high mortality rate in low-income countries. In sub-Saharan Africa, most breast cancer patients are diagnosed with advanced disease. Some studies have quantified the time delay to diagnosis in sub-Saharan Africa, but very few have used qualitative methods to understand barriers leading to delay. This study analyses barriers throughout a breast cancer patient's pathway from symptom recognition to treatment in Mali. METHOD: Three focus group discussions were conducted. The model of pathways to treatment was used to structure the results into 4 time intervals: appraisal, help-seeking, diagnosis, and treatment, with a focus on barriers during each interval. RESULTS: The main barriers during the appraisal interval were a low level of breast cancer knowledge among women, their families, and medical professionals, and during the help-seeking interval, mistrust in the community health care centers and economic hardship. Barriers during the diagnosis interval were low quality of health care services and lack of social support, and during the pretreatment interval high costs and lack of specialized services. CONCLUSION: Multilevel interventions are needed to ensure access, availability, and affordability of a minimum standard of care for breast cancer patients in sub-Saharan Africa.