scholarly journals Difference in Risk Factors for Breast Cancer by ER Status in an Indigenous African Population

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
M. Galukande ◽  
H. Wabinga ◽  
F. Mirembe ◽  
C. Karamagi ◽  
A. Asea

Introduction. Breast cancer is the commonest cancer among women globally. In Uganda, it is on the rise, projected at a 4.5% annual ASR increase (age standardized incidence rate). The reasons for this steep increase are not fully established. In the recent past, gene profiling in tumor tissues suggests that breast cancers are divided into subtypes dependent on the presence or absence of oestrogen receptor, progesterone, and human epidermal growth factor receptor 2 (HER 2). These subtypes do have distinctive clinical outcomes and perhaps risk factors from past studies. There is paucity of data on hormonal receptor status and the traditionally known risk factors in sub-Saharan Africa. The purpose of this study therefore was to establish the differences between ER status and the traditionally known risk factors for breast cancer in Uganda. Methods. An observational analytical hospital, based study, carried out at Makerere University, College of Health Sciences. Formalin fixed and paraffin imbedded sections were prepared for haemotoxylin and eosin (H&E) stains and immunohistochemistry (IHC). Ethical approval was obtained. Results. A total of 113 women were recruited. Mean age was 45 years (SD14). There were no significant differences in selected risk factors (setting, age, contraceptive use, parity, breast feeding, or menarche) by ER status although ER negative tumors had significantly higher grade tumors (by a factor of two) compared to ER positive tumors. Conclusion. There were no significant differences among risk factors by ER status contrary to what several other studies suggest. The manifestation of breast cancer in Africa warrants further extensive inquiry.

Author(s):  
Mariana Brandão ◽  
Assucena Guisseve ◽  
Albertino Damasceno ◽  
Genoveva Bata ◽  
Carla Silva-Matos ◽  
...  

2021 ◽  
pp. 153537022110060
Author(s):  
Claudia A Anyigba ◽  
Gordon A Awandare ◽  
Lily Paemka

Breast cancer is the commonest cause of global cancer-related deaths in women and a public health burden in sub-Saharan Africa (SSA). Although the disease incidence in SSA seems lower, mortality rates are disproportionately high in comparison to high-income countries. The global disease burden is growing, with SSA reporting the majority of cases; however, the dearth of information results in insufficient data which is barely representative of the actual disease burden in this population. Future incidence predictions assign the subregion with a majority of the cases and associated deaths. Breast cancer presents with racial and ethnic variations, and available evidence suggests geographical diversity and persistent risk factors that have barely been explored in SSA. Breast cancer is a complex genetic disease, but the genetic risk factors in the extant African population, which is the most genetically diverse population, is scant and of low quality. This review focuses on the burden, prevalence, detection, treatment, survival, biology, as well as risk factors, and reinforces the need for breast cancer-associated risk factor investigation and population-specific studies in SSA.


2020 ◽  
Vol 12 ◽  
pp. 175883592094625
Author(s):  
Priyakshi Kalita-de Croft ◽  
Malcolm Lim ◽  
Haarika Chittoory ◽  
Xavier M. de Luca ◽  
Jamie R. Kutasovic ◽  
...  

Background: Human epidermal growth factor receptor-4 (HER4) and yes-associated protein-1 (YAP) are candidate therapeutic targets in oncology. YAP’s transcriptional coactivation function is modulated by the HER4 intracellular domain (HER4-ICD) in vitro, but the clinical relevance of this has not been established. This study investigated the potential for targeting the HER4-YAP pathway in brain metastatic breast cancer. Methods: We performed immuno-phenotypic profiling of pathway markers in a consecutive breast cancer series with 25 years of clinical follow up ( n = 371), and patient-matched breast and metastatic brain tumours ( n = 91; 30 pairs). Results: Membrane localisation of phospho-HER4 [pHER4(Y1162)] was infrequent in primary breast cancer, but very frequent in brain metastases (5.9% versus 75% positive), where it was usually co-expressed with pHER3(Y1289) ( p < 0.05). The presence of YAP in tumour cell nuclei was associated directly with nuclear pERK5(T218/Y210) ( p = 0.003). However, relationships with disease-specific survival depended on oestrogen receptor (ER) status. Nuclear pYAP(S127) was associated with smaller, good prognostic ER+ breast tumours (log-rank hazard-ratio 0.53; p = 9.6E−03), but larger, poor prognostic triple-negative cancers (log-rank hazard-ratio 2.78; p = 1.7E−02), particularly when co-expressed with nuclear HER4-ICD ( p = 0.02). This phenotype was associated with stemness and mitotic instability markers (vimentin, SOX9, ID1, SPAG5, TTK, geminin; p < 0.05). YAP expression in brain metastases was higher than matched primary tumours; specifically, nuclear pYAP(S127) in ER-negative cases ( p < 0.05). Nuclear YAP was detected in ~70% of ER-negative, HER4-activated brain metastases. Discussion: Our findings suggest that the canonical-mechanism where Hippo pathway-mediated phosphorylation of YAP ostensibly excludes it from the nucleus is dysfunctional in breast cancer. The data are consistent with pYAP(S127) having independent transcriptional functions, which may include transducing neuregulin signals in brain metastases. Consistent with mechanistic studies implicating it as an ER co-factor, nuclear pYAP(S127) associations with breast cancer clinical outcomes were dependent on ER status. Conclusion: Preclinical studies investigating HER4 and nuclear YAP combination therapy strategies are warranted.


2015 ◽  
Vol 33 (9) ◽  
pp. 1030-1037 ◽  
Author(s):  
Johanna Holm ◽  
Keith Humphreys ◽  
Jingmei Li ◽  
Alexander Ploner ◽  
Abbas Cheddad ◽  
...  

Purpose To compare tumor characteristics and risk factors of interval breast cancers and screen-detected breast cancers, taking mammographic density into account. Patients and Methods Women diagnosed with invasive breast cancer from 2001 to 2008 in Stockholm, Sweden, with data on tumor characteristics (n = 4,091), risk factors, and mammographic density (n = 1,957) were included. Logistic regression was used to compare interval breast cancers with screen-detected breast cancers, overall and by highest and lowest quartiles of percent mammographic density. Results Compared with screen-detected breast cancers, interval breast cancers in nondense breasts (≤ 20% mammographic density) were significantly more likely to exhibit lymph node involvement (odds ratio [OR], 3.55; 95% CI, 1.74 to 7.13) and to be estrogen receptor negative (OR, 4.05; 95% CI, 2.24 to 7.25), human epidermal growth factor receptor 2 positive (OR, 5.17; 95% CI, 1.64 to 17.01), progesterone receptor negative (OR, 2.63; 95% CI, 1.58 to 4.38), and triple negative (OR, 5.33; 95% CI, 1.21 to 22.46). In contrast, interval breast cancers in dense breasts (> 40.9% mammographic density) were less aggressive than interval breast cancers in nondense breasts (overall difference, P = .008) and were phenotypically more similar to screen-detected breast cancers. Risk factors differentially associated with interval breast cancer relative to screen-detected breast cancer after adjusting for age and mammographic density were family history of breast cancer (OR, 1.32; 95% CI, 1.02 to 1.70), current use of hormone replacement therapy (HRT; OR, 1.84; 95% CI, 1.38 to 2.44), and body mass index more than 25 kg/m2 (OR, 0.49; 95% CI, 0.29 to 0.82). Conclusion Interval breast cancers in women with low mammographic density have the most aggressive phenotype. The effect of HRT on interval breast cancer risk is not fully explained by mammographic density. Family history is associated with interval breast cancers, possibly indicating disparate genetic background of screen-detected breast cancers and interval breast cancers.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Hafte Kahsay Kebede ◽  
Lillian Mwanri ◽  
Paul Ward ◽  
Hailay Abrha Gesesew

Abstract Background It is known that ‘drop out’ from human immunodeficiency virus (HIV) treatment, the so called lost-to-follow-up (LTFU) occurs to persons enrolled in HIV care services. However, in sub-Saharan Africa (SSA), the risk factors for the LTFU are not well understood. Methods We performed a systematic review and meta-analysis of risk factors for LTFU among adults living with HIV in SSA. A systematic search of literature using identified keywords and index terms was conducted across five databases: MEDLINE, PubMed, CINAHL, Scopus, and Web of Science. We included quantitative studies published in English from 2002 to 2019. The Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used for methodological validity assessment and data extraction. Mantel Haenszel method using Revman-5 software was used for meta-analysis. We demonstrated the meta-analytic measure of association using pooled odds ratio (OR), 95% confidence interval (CI) and heterogeneity using I2 tests. Results Thirty studies met the search criteria and were included in the meta-analysis. Predictors of LTFU were: demographic factors including being: (i) a male (OR = 1.2, 95% CI 1.1–1.3, I2 = 59%), (ii) between 15 and 35 years old (OR = 1.3, 95% CI 1.1–1.3, I2 = 0%), (iii) unmarried (OR = 1.2, 95% CI 1.2–1.3, I2 = 21%), (iv) a rural dweller (OR = 2.01, 95% CI 1.5–2.7, I2 = 40%), (v) unemployed (OR = 1.2, 95% CI 1.04–1.4, I2 = 58%); (vi) diagnosed with behavioral factors including illegal drug use(OR = 13.5, 95% CI 7.2–25.5, I2 = 60%), alcohol drinking (OR = 2.9, 95% CI 1.9–4.4, I2 = 39%), and tobacco smoking (OR = 2.6, 95% CI 1.6–4.3, I2 = 74%); and clinical diagnosis of mental illness (OR = 3.4, 95% CI 2.2–5.2, I2 = 1%), bed ridden or ambulatory functional status (OR = 2.2, 95% CI 1.5–3.1, I2 = 74%), low CD4 count in the last visit (OR = 1.4, 95% CI 1.1–1.9, I2 = 75%), tuberculosis co-infection (OR = 1.2, 95% CI 1.02–1.4, I2 = 66%) and a history of opportunistic infections (OR = 2.5, 95% CI 1.7–2.8, I2 = 75%). Conclusions The current review identifies demographic, behavioral and clinical factors to be determinants of LTFU. We recommend strengthening of HIV care services in SSA targeting the aforementioned group of patients. Trial registration Protocol: the PROSPERO Registration Number is CRD42018114418


BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e039456
Author(s):  
Leolin Katsidzira ◽  
Wisdom F Mudombi ◽  
Rudo Makunike-Mutasa ◽  
Bahtiyar Yilmaz ◽  
Annika Blank ◽  
...  

IntroductionThe epidemiology of inflammatory bowel disease (IBD) in sub-Saharan Africa is poorly documented. We have started a registry to determine the burden, phenotype, risk factors, disease course and outcomes of IBD in Zimbabwe.Methods and analysisA prospective observational registry with a nested case–control study has been established at a tertiary hospital in Harare, Zimbabwe. The registry is recruiting confirmed IBD cases from the hospital, and other facilities throughout Zimbabwe. Demographic and clinical data are obtained at baseline, 6 months and annually. Two age and sex-matched non-IBD controls per case are recruited—a sibling or second-degree relative, and a randomly selected individual from the same neighbourhood. Cases and controls are interviewed for potential risk factors of IBD, and dietary intake using a food frequency questionnaire. Stool is collected for 16S rRNA-based microbiota profiling, and along with germline DNA from peripheral blood, is being biobanked. The estimated sample size is 86 cases and 172 controls, and the overall registry is anticipated to run for at least 5 years. Descriptive statistics will be used to describe the demographic and phenotypic characteristics of IBD, and incidence and prevalence will be estimated for Harare. Risk factors for IBD will be analysed using conditional logistic regression. For microbial analysis, alpha diversity and beta diversity will be compared between cases and controls, and between IBD phenotypes. Mann-Whitney U tests for alpha diversity and Adonis (Permutational Multivariate Analysis of Variance) for beta diversity will be computed.Ethics and disseminationEthical approval has been obtained from the Parirenyatwa Hospital’s and University of Zimbabwe’s research ethics committee and the Medical Research Council of Zimbabwe. Findings will be discussed with patients, and the Zimbabwean Ministry of Health. Results will be presented at scientific meetings, published in peer reviewed journals, and on social media.Trial registration numberNCT04178408.


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