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.

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.

Fine needle aspiration cytology in Mozambique: Report of a 15-year experience.

BACKGROUND: Fine needle aspiration cytology (FNAC) is an important diagnostic tool in a range of medical settings. It is fast, quick and a highly accurate diagnostic method and can be used, in settings with minimal laboratory infrastructures. METHODS: In this report, we describe the experience in the use of FNAC since it is introduction in 1996 in the Anatomical Pathology Service of the Maputo Central Hospital (MCH), along with more detailed data referring to 2009-2010. RESULTS: The number of FNAC analyses increased gradually from 269 (4.1% of all pathologic tests of the Service) in 1996, when it was introduced in Mozambique, to 3234 (17% of all tests) in 2010. Lymph nodes were the organs most frequently biopsied, followed by breast and soft tissues. Inflammatory conditions, especially tuberculosis, were the most frequent diagnoses (22.2% of the cases), followed by hyperplastic conditions (20.6%), benign tumors (13.4%) and malignant tumors (12.3%). CONCLUSION: Our results clearly demonstrate that even in an environment with poor laboratory resources, it is possible to establish a FNAC clinic that can provide a quick and precise diagnosis for clinicians to aid in early treatment interventions, especially in inflammatory diseases which were the majority of our cases.

Mycobacterium tuberculosis causing tuberculous lymphadenitis in Maputo, Mozambique.

BACKGROUND: The zoonosis bovine tuberculosis (TB) is known to be responsible for a considerable proportion of extrapulmonary TB. In Mozambique, bovine TB is a recognised problem in cattle, but little has been done to evaluate how Mycobacterium bovis has contributed to human TB. We here explore the public health risk for bovine TB in Maputo, by characterizing the isolates from tuberculous lymphadenitis (TBLN) cases, a common manifestation of bovine TB in humans, in the Pathology Service of Maputo Central Hospital, in Mozambique, during one year. RESULTS: Among 110 patients suspected of having TBLN, 49 had a positive culture result. Of those, 48 (98%) were positive for Mycobacterium tuberculosis complex and one for nontuberculous mycobacteria. Of the 45 isolates analysed by spoligotyping and Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR), all were M. tuberculosis. No M. bovis was found. Cervical TBLN, corresponding to 39 (86.7%) cases, was the main cause of TBLN and 66.7% of those where from HIV positive patients. We found that TBLN in Maputo was caused by a variety of M. tuberculosis strains. The most prevalent lineage was the EAI (n = 19; 43.2%). Particular common spoligotypes were SIT 48 (EAI1_SOM sublineage), SIT 42 (LAM 9), SIT 1 (Beijing) and SIT53 (T1), similar to findings among pulmonary cases. CONCLUSIONS: M. tuberculosis was the main etiological agent of TBLN in Maputo. M. tuberculosis genotypes were similar to the ones causing pulmonary TB, suggesting that in Maputo, cases of TBLN arise from the same source as pulmonary TB, rather than from an external zoonotic source. Further research is needed on other forms of extrapulmonary TB and in rural areas where there is high prevalence of bovine TB in cattle, to evaluate the risk of transmission of M. bovis from cattle to humans.

Keratins 8, 10, 13, and 17 are useful markers in the diagnosis of human cervix carcinomas.

Several candidate tumor markers for cervical neoplasia have been identified. Among those are keratin markers, whose precise implications in the diagnosis are still under debate. In the present study, we aimed to clarify the usefulness of studying the expression of keratins 8, 10, 13, and 17 for diagnostic purposes in human cervix carcinomas. Forty-four invasive squamous carcinomas, 10 cervical intraepithelial neoplasia grade III (CIN III), and 10 reference cervix were examined immunohistochemically with monoclonal antibodies. Expression of keratins in reference exocervix, CIN III, and invasive carcinomas was as follows: keratin 8--0, 44.4%, and 57.1%, respectively; keratin 10-77.8%, 40%, and 19%, respectively; keratin 13--100%, 22.2%, and 25%, respectively; keratin 17-0, 40%, and 73.2%, respectively. In invasive carcinomas, expression of keratin 10 was significantly associated with keratinizing carcinomas. In conclusion, we observed that expression of keratins 8 and 17 and loss of keratins 10 and 13 are good markers of malignant transformation in human cervix. Keratin expression patterns, namely expression of keratin 10, can be useful for subtyping and grading squamous cell carcinomas of the cervix.

Characterization of human papillomavirus infection, P53 and Ki-67 expression in cervix cancer of Mozambican women.

In this study, we aimed at evaluating the distribution of HPV types and the expression of P53 and Ki-67 in cervix carcinomas of Mozambican women. Fourty-seven invasive carcinomas, 10 CIN III, and 10 normal cervix were studied. P53 and Ki-67 expression was examined immunohistochemically. HPV infection and HPV types were detected by PCR (GP5+/bio-GP6+) and enzyme-immunoassay, respectively. Expression of P53 and Ki-67 and detection of HPV were as follows: normal cervix--0%, 10%, and 0%, respectively; CIN III--10%, 0%, and 100%, respectively; invasive carcinomas--50%, 55.5%, and 70%, respectively. HPV 16 was identified in 54% of invasive carcinomas, HPV 31, 33, 35, and 45 in 23%, "unidentified" HPV in 19%, and HPV 18 in 4% of invasive carcinomas. No significant associations were observed between P53 expression, Ki-67 expression, and HPV infection. In conclusion, we observed a high frequency of HPV infection in CIN III lesions and invasive carcinomas from Mozambican women, with HPV 16 representing the most frequent viral type. HPV status was not related to P53 and Ki-67 expression. Both P53 and Ki-67 are associated with invasive cervix carcinomas, mainly of the squamous keratinizing histotype.

Oftalmoplegia por toxoplasmose em paciente com AIDS: relato de caso e revisäo da literatura / Ophthalmoplegy by toxoplasmosis in patients with AIDS: a case report and literature review

Os autores relatam um caso de oftalmoplegia bilateral decorrente de provável toxoplasmose no tronco cerebral, em um paciente de 37 anos, com sorologia positiva para HIV, que respondeu favoravelmente ao tratamento com sulfadiazina e pirimetamina