Risk Factors for Breast Cancer, Overall and by Tumor Subtype, among Women from Mozambique, Sub-Saharan Africa.

BACKGROUND: Breast cancer incidence is rising in Africa, but there are scare data regarding risk factors in this region. We assessed the relation between risk factors and the occurrence of breast cancer, overall and by tumor subtype in women from Mozambique. METHODS: The associations between education, number of births, height, weight, body mass index (BMI), and breast cancer risk among 138 cases (participants from the Moza-BC cohort) and 638 controls from the general population (from a World Health Organization stepwise approach to surveillance survey), recruited during 2014 to 2017, were investigated. Adjusted ORs (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. RESULTS: Multiparity (≥6 vs. 0-1 live births) was a protective factor for the development of hormone receptor (HR)-positive (aOR = 0.22; 95% CI, 0.08-0.64) and HR-positive/HER2-negative tumors (aOR = 0.20; 95% CI, 0.06-0.68), whereas a higher educational level (≥8 vs. 0 schooling years) increased breast cancer risk across all subtypes (overall aOR = 1.98; 95% CI, 1.04-3.80). Higher weight and BMI were associated with a higher breast cancer risk among postmenopausal women (per 1-kg increase: aOR = 1.05; 95% CI, 1.02-1.08; per 1-kg/m2 increase: aOR = 1.11; 95% CI, 1.04-1.18, respectively), but were protective in premenopausal women (aOR = 0.98; 95% CI, 0.96-0.99; aOR = 0.95; 95% CI, 0.91-0.99, respectively), regardless of subtype. Higher height increased the risk of HR-negative tumors in postmenopause (per 10-cm increase: aOR = 2.81; 95% CI, 1.41-6.03). CONCLUSION: These results demonstrate the etiological heterogeneity of breast cancer among native African women, namely regarding the differential effect of multiparity, education, and body parameters in breast cancer risk. IMPACT: As the prevalence of obesity grows, these findings are important to inform public health policies on cancer prevention, by highlighting obesity as a modifiable risk factor for breast cancer among African women.

Comparing the cost of non-metastatic breast cancer care in a low-income vs a high-income country: A plea for an optimal allocation of health resources in Sub-Saharan Africa.

Breast cancer incidence is rising in low-income countries, but there is limited information regarding health resource allocation for its care. We assessed the cost of care during the first three years after diagnosis in a low-income country (Mozambique; n = 162 women) and compared it with a high-income country (Portugal, n = 703 women). Local currency prices were converted to 2019 international dollars (Int$). In Mozambique, the median cost was lower than in Portugal (2888 vs 18,533 Int$, respectively) and did not vary across stage or tumor subtype. These findings may help improving resource allocation for breast cancer care in Sub-Saharan Africa, despite reflecting an underfunding of treatment in this setting.

Survival Impact and Cost-Effectiveness of a Multidisciplinary Tumor Board for Breast Cancer in Mozambique, Sub-Saharan Africa.

BACKGROUND: Despite the international endorsement of multidisciplinary tumor boards (MTBs) for breast cancer care, implementation is suboptimal worldwide, and evidence regarding their effectiveness in developing countries is lacking. We assessed the impact on survival and the cost-effectiveness of implementing an MTB in Mozambique, sub-Saharan Africa. MATERIALS AND METHODS: This prospective cohort study included 205 patients with breast cancer diagnosed between January 2015 and August 2017 (98 before and 107 after MTB implementation), followed to November 2019. Pre- and post-MTB implementation subcohorts were compared for clinical characteristics, treatments, and overall survival. We used hazard ratios and 95% confidence intervals (CI), computed by Cox proportional hazards regression. The impact of MTB implementation on the cost per quality-adjusted life year (QALY) was estimated from the provider perspective. RESULTS: We found no significant differences between pre- and post-MTB subcohorts regarding clinical characteristics or treatments received. Among patients with early breast cancer (stage 0-III; n = 163), the 3-year overall survival was 48.0% (95% CI, 35.9-59.1) in the pre-MTB and 73.0% (95% CI, 61.3-81.6) in the post-MTB subcohort; adjusted hazard ratio, 0.47 (95% CI, 0.27-0.81). The absolute 3-year mean cost increase was $119.83 per patient, and the incremental cost-effectiveness ratio was $802.96 per QALY, corresponding to 1.6 times the gross domestic product of Mozambique. CONCLUSION: The implementation of a MTB in Mozambique led to a 53% mortality decrease among patients with early breast cancer, and it was cost-effective. These findings highlight the feasibility of implementing this strategy and the need for scaling-up MTBs in developing countries, as a way to improve patient outcomes. IMPLICATIONS FOR PRACTICE: Currently, more than half of the deaths from breast cancer in the world occur in developing countries. Strategies that optimize care and that are adjusted for available resources are needed to improve the outcomes of patients with breast cancer in these regions. The discussion of cases at multidisciplinary tumor boards (MTBs) may improve survival outcomes, but implementation is suboptimal worldwide, and evidence regarding their effectiveness in developing countries is lacking. This study evaluated the impact of implementing an MTB on the care and survival of patients with breast cancer in Mozambique, sub-Saharan Africa and its cost-effectiveness in this low-income setting.

Breast cancer subtypes: implications for the treatment and survival of patients in Africa-a prospective cohort study from Mozambique.

BACKGROUND: Data regarding breast cancer epidemiology, treatment and survival in Africa are scarce. We aimed to assess the distribution of breast cancer subtypes in Mozambique and its impact on patients' treatment and survival. The concordance of biomarker assessment between cytological and histological samples was also evaluated. METHODS: Prospective cohort study including 210 patients diagnosed between January 2015 and August 2017, followed to November 2019. Clinicopathological characteristics, treatment, 3-year overall survival (OS) and disease-free survival (DFS) were compared across classic tumour subtypes (oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive and triple-negative breast cancer (TNBC)) and surrogate intrinsic subtypes (St. Gallen classification). Concordance was measured using Cohen's κ statistics. RESULTS: A total of 51% of patients had ER-positive/HER2-negative tumours, 24% HER2-positive and 25% TNBC. Concordance between cytological and histological samples regarding ER and HER2 status was substantial (κ=0.762 and κ=0.603, respectively). There were no significant differences across subtypes regarding clinical characteristics and treatment, except for HIV positivity and high histological grade (more prevalent among TNBC) or endocrine therapy (higher use among ER-positive/HER2-negative and HER2-positive patients). Three-year OS was 52.5% (95% CI, 44.3% to 60.0%), being higher in ER-positive/HER2-negative (61.1%) compared with HER2-positive (53.2%) and TNBC (31.9%) patients. Adjusted HRs were 1.96 (95% CI, 1.13 to 3.39) among HER2-positive and 3.10 (95% CI, 1.81 to 5.31) among TNBC versus ER-positive/HER2-negative patients. Three-year DFS was 46.6% (95% CI, 38.0% to 54.8%), being lower among TNBC versus ER-positive/HER2-negative patients (HR 2.91; 95% CI, 1.64 to 5.16). Results were similar between surrogate intrinsic subtypes. CONCLUSION: There was a high proportion of HER2-positive and TNBC among Mozambican patients and their survival was poor compared with ER-positive/HER2-negative patients, partly due to the limited treatment options. A systematic assessment of ER, PR and HER2 status is feasible and may help tailoring and optimise the treatment of patients with breast cancer in low-resource settings, potentially leading to survival gains in this underserved population.

Clinico-pathological discrepancies in the diagnosis of causes of death in adults in Mozambique: A retrospective observational study.

BACKGROUND: Clinico-pathological discrepancies are more frequent in settings in which limited diagnostic techniques are available, but there is little information on their actual impact. AIM: We assessed the accuracy of the clinical diagnoses in a tertiary referral hospital in sub-Saharan Africa by comparison with post-mortem findings. We also identified potential risk factors for misdiagnoses. METHODS: One hundred and twelve complete autopsy procedures were performed at the Maputo Central Hospital (Mozambique), from November 2013 to March 2015. We reviewed the clinical records. Major clinico-pathological discrepancies were assessed using a modified version of the Goldman and Battle classification. RESULTS: Major diagnostic discrepancies were detected in 65/112 cases (58%) and were particularly frequent in infection-related deaths (56/80 [70%] major discrepancies). The sensitivity of the clinical diagnosis for toxoplasmosis was 0% (95% CI: 0-37), 18% (95% CI: 2-52) for invasive fungal infections, 25% (95% CI: 5-57) for bacterial sepsis, 34% (95% CI: 16-57), for tuberculosis, and 46% (95% CI: 19-75) for bacterial pneumonia. Major discrepancies were more frequent in HIV-positive than in HIV-negative patients (48/73 [66%] vs. 17/39 [44%]; p = 0.0236). CONCLUSIONS: Major clinico-pathological discrepancies are still frequent in resource constrained settings. Increasing the level of suspicion for infectious diseases and expanding the availability of diagnostic tests could significantly improve the recognition of common life-threatening infections, and thereby reduce the mortality associated with these diseases. The high frequency of clinico-pathological discrepancies questions the validity of mortality reports based on clinical data or verbal autopsy.

Clinico-pathological discrepancies in the diagnosis of causes of death in adults in Mozambique: A retrospective observational study

Background Clinico-pathological discrepancies are more frequent in settings in which limited diagnostic techniques are available, but there is little information on their actual impact. Aim We assessed the accuracy of the clinical diagnoses in a tertiary referral hospital in sub-Saharan Africa by comparison with post-mortem findings. We also identified potential risk factors for misdiagnoses. Methods One hundred and twelve complete autopsy procedures were performed at the Maputo Central Hospital (Mozambique), from November 2013 to March 2015. We reviewed the clinical records. Major clinico-pathological discrepancies were assessed using a modified version of the Goldman and Battle classification. Results Major diagnostic discrepancies were detected in 65/112 cases (58%) and were particularly frequent in infection-related deaths (56/80 [70%] major discrepancies). The sensitivity of the clinical diagnosis for toxoplasmosis was 0% (95% CI: 0­37), 18% (95% CI: 2­52) for invasive fungal infections, 25% (95% CI: 5­57) for bacterial sepsis, 34% (95% CI: 16­57), for tuberculosis, and 46% (95% CI: 19­75) for bacterial pneumonia. Major discrepancies were more frequent in HIV-positive than in HIV-negative patients (48/73 [66%] vs. 17/39 [44%]; p = 0.0236). Conclusions Major clinico-pathological discrepancies are still frequent in resource constrained settings. Increasing the level of suspicion for infectious diseases and expanding the availability of diagnostic tests could significantly improve the recognition of common life-threatening infections, and thereby reduce the mortality associated with these diseases. The high frequency of clinico-pathological discrepancies questions the validity of mortality reports based on clinical data or verbal autopsy.

Hepatocellular carcinoma: Clinical-pathological features and HIV infection in Mozambican patients.

BACKGROUND AND AIMS: Mozambique had been ranked among the countries with the highest global incidence of HCC with chronic hepatitis B infection and high exposure to aflatoxin-B1 (AFB1) being major risk factors. Indeed, HCC remains one of the most frequent cancer in Maputo. On the other hand, Mozambique has a high prevalence of infection with Human Immunodeficiency virus (HIV). Our study aims to describe the epidemiology, clinicopathological and serological features of patients with HCC in Maputo Central Hospital and its relationship with HIV. METHODS: A series of 206 patients, diagnosed with HCC via fine needle aspiration, were consecutively included in the study. Patient data was collected using a questionnaire and all patients were tested for HBV, HCV, HIV. RESULTS: Median age was 49 years old and the M: F sex ratio was 2.4. A total of 114 (56.2%) of the patients were HBsAg positive. Hepatitis C antibodies were present in 8.9% of cases, and co-infection with HBV and HCV (HBsAg/anti-HCV) was observed in 4 (2.0%) cases. The remainder, 36.3%, were neither hepatitis B- nor C-related. HIV was detected in 34 cases (18.0%) cases. HIV-HBV or HIV-HCV co-infections were observed in 22 (68.8%) and 2 (6.2%) cases. Overall, positivity for HIV was associated with younger age, and especially in patients with HBsAg+/anti-HCV+. CONCLUSIONS: Our data emphasize the need for a reinforcement of secondary prevention measures in Mozambique. Serological screening for HBV in people born before universal anti-hepatitis B immunization (2001), effective screening, and specific management in HIV(+) patients are urgently needed.

Hepatocellular Carcinoma: Clinical-pathological features and HIV infection in Mozambican patients

Mozambique had been ranked among the countries with the highest global incidence of HCC with chronic hepatitis B infection and high exposure to aflatoxin-B1 (AFB1) being major risk factors. Indeed, HCC remains one of the most frequent cancer in Maputo. On the other hand, Mozambique has a high prevalence of infection with Human Immunodeficiency virus (HIV). Our study aims to describe the epidemiology, clinicopathological and serological features of patients with HCC in Maputo Central Hospital and its relationship with HIV. A series of 206 patients, diagnosed with HCC via fine needle aspiration, were consecutively included in the study. Patient data was collected using a questionnaire and all patients were tested for HBV, HCV, HIVMedian age was 49 years old and the M: F sex ratio was 2.4. A total of 114 (56.2%) of the patients were HBsAg positive. Hepatitis C antibodies were present in 8.9% of cases, and coinfection with HBV and HCV (HBsAg/anti-HCV) was observed in 4 (2.0%) cases. The remainder, 36.3%, were neither hepatitis B- nor C-related. HIV was detected in 34 cases (18.0%) cases. HIVHBV or HIV-HCV co-infections were observed in 22 (68.8%) and 2 (6.2%) cases. Overall, positivity for HIV was associated with younger age, and especially in patients with HBsAg+/antiHCV+. Our data emphasize the need for a reinforcement of secondary prevention measures in Mozambique. Serological screening for HBV in people born before universal antihepatitis B immunization (2001), effective screening, and specific management in HIV(+) patients are urgently needed.

Postmortem Interval and Diagnostic Performance of the Autopsy Methods.

Postmortem studies, including the complete diagnostic autopsy (CDA) and the minimally invasive autopsy (MIA), an innovative approach to post-mortem sampling and cause of death investigation, are commonly performed within 24 hours after death because the quality of the tissues deteriorates over time. This short timeframe may hamper the feasibility of the procedure. In this study, we compared the diagnostic performance of the two postmortem procedures when carried out earlier and later than 24 hours after death, as well as the impact of increasing postmortem intervals (PMIs) on the results of the microbiological tests in a series of 282 coupled MIA/CDA procedures performed at the Maputo Central Hospital in Mozambique between 2013 and 2015. 214 procedures were conducted within 24 hours of death (early autopsies), and 68 after 24 hours of death (late autopsies). No significant differences were observed in the number of non-conclusive diagnoses (2/214 [1%] vs. 1/68 [1%] p = 0.5645 for the CDA; 27/214 [13%] vs. 5/68 [7%] p = 0.2332 for the MIA). However, increasing PMIs were associated with a raise in the number of bacteria identified (rate: 1.014 per hour [95%CI: 1.002-1.026]; p = 0.0228). This increase was mainly due to rising numbers of bacteria of the Enterobacteriaceae family and Pseudomonas genus strains. Thus, performing MIA or CDA more than 24 hours after death can still render reliable diagnostic results, not only for non-infectious conditions but also for many infectious diseases, although, the contribution of Enterobacteriaceae and Pseudomonas spp. as etiological agents of infections leading to death may be overestimated.

Descrição das características clínico-patológicas e de expressão do hhv-8 em pacientes com sarcoma de kaposi atendidos no serviço de dermatologia do hospital central de maputo, moçambique / Description of hhv-8 clinical-pathological and expression characteristics in kaposi sarcoma patients attended in the dermatology service of maputo central hospital, mozambique

Resumo O Sarcoma de Kaposi (SK) é um tumor vascular de baixo grau do sangue e dos vasos linfáticos, com evolução clínica muito variável, que frequentemente se apresenta na forma de lesões cutâneas; Histologicamente caracteriza-se por proliferação de vasos sanguíneos, de células fusiformes, inflamação e edema. A incidência deste tumor está aumentada em indivíduos HIV positivos. Nestes doentes, o HIV tem mudado a forma de apresentação do SK, tornando numa doença agressiva que se caracteriza por disseminação, mudanças de apresentação histológicas das lesões, aumento da carga viral do HHV-8 e progressão rápida. Com a descoberta do HHV-8, o genoma viral tem sido detectado em todas as formas de SK. O antígeno associado a latência (LANA) é usada como marcador de infecção pelo HHV-8, e a sua presença é demonstrada nas biópsias das lesões do SK. No nosso estudo utilizamos a técnica de imuno - histoquímica para caracterizar e quantificar o HHV-8 nas lesões, de forma a caracterizar a agressividade clínica e morfológica do SK. Os doentes incluídos no estudo apresentaram na sua maioria Sarcoma de Kaposi associado ao HIV (n=109; 94,8%) e sem TARV (n=88; 80.7%), apesar de estarem imunologicamente comprometidos. A imunodeficiência verificada foi caracterizada pela diminuição no número de células TCD4+ (mediana - 284.5 células/mm3) e carga viral do HIV (mediana - 7741.73cópias /ml). As lesões de SK foram maioritariamente observadas nos membros inferiores (n=105; 91.3%) e com disseminação múltipla pelo corpo. O diagnóstico histológico foi marcado pelos estágios precoces, com maior representação de lesões em placa (n=56; 48.7%). A expressão imunohistoquímica do LANA/HHV-8 nestas lesões foi aumentada nos estágios tumorais (nódulo), quando comparadas com outros estágios. No entanto, a expressão do HHV-8 não se correlacionou com estado de imunodeficiência, mas está inversamente relacionada com a agressividade clínica observada, o que sugere que uma pequena quantidade de vírus no tecido possa ser suficiente para fazer com que o SK tome características agressivas em indivíduos co - infectados com HIV e com grau de imunodeficiência grave. O nosso estudo mostra que apesar da agressividade clínica dada pelo número de lesões do SK se relacionar com a menor densidade do vírus no tecido com lesão, esta está associada com o tempo de aparecimento das lesões em relação ao tempo de diagnóstico ou inclusão no estudo. Palavras chave ­ LANA, HHV-8, Sarcoma de Kaposi (SK), Imunohistoquímica

Kaposi's sarcoma (KS) is a vascular tumor of low grade blood and lymphatic vessels, with highly variable clinical course, also presenting skin lesions; histologically it is characterized by proliferation of blood vessels, spindle cells, inflammation and edema. The incidence of this tumor is high in people affected with HIV. In these patients, HIV has changed the format of the SK, becoming an aggressive disease that is characterized by spreading and changes in the histological appearance of the lesions, increased viral load of HHV-8 and rapid progression. With the discovery of HHV-8, this viral genome has been detected in all forms of SK. The latency-associated antigen (LANA) is used as a marker of infection with HHV-8, and its presence is demonstrated in biopsies of KS lesions. In our study, we used Immunohistochemistry to characterize and quantify HHV-8 in the lesions in order to characterize the morphological and clinical aggressiveness of KS. Most of the patients enrolled in this study presents Kaposi's sarcoma associated with HIV (n = 109, 94.8%) and without antiretroviral therapy(n = 88, 80.7%), although they are immunologically compromised. The verified immunodeficiency was characterized by reduction in the number of CD4 + level (median -284.5 cells/mm3) and HIV viral load (median -7741.73cop/ ml). The KS lesions were mostly seen in the lower limbs (n = 105, 91.3%) and multiple spreads over the body. The histological diagnostic was scored by the early stages, with higher representation of lesions in plaque (n=56,48.7%). The Immune histochemical expression of LANA/HHV-8 in these lesions was high in tumor stage (node), when compared with other stages. However, the expression of HHV-8 did not correlate with immunodeficiency state, but is inversely related to the observed clinical aggressiveness, suggesting that a small amount of virus in tissue can be sufficient for SK to present aggressive characteristics in individual's co -infected with HIV and severe degree of immunodeficiency. This study shows that despite the clinical aggressiveness given by the number of KS lesions be related to the lower density of the virus in tissue with injury, this is associated with the time of lesions appearance in relation to the time of diagnosis or enrollment.