Mosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study.

Epidemiologic data on insecticide exposures and breast cancer risk are inconclusive and mostly from high-income countries. Using data from 1071 invasive pathologically confirmed breast cancer cases and 2096 controls from the Ghana Breast Health Study conducted from 2013 to 2015, we investigated associations with mosquito control products to reduce the spread of mosquito-borne diseases, such as malaria. These mosquito control products were insecticide-treated nets, mosquito coils, repellent room sprays, and skin creams for personal protection against mosquitos. Multivariable and polytomous logistic regression models were used to estimate odds ratios (ORadj) and 95% confidence intervals (CI) with breast cancer risk-adjusted for potential confounders and known risk factors. Among controls, the reported use of mosquito control products were mosquito coils (65%), followed by insecticide-treated nets (56%), repellent room sprays (53%), and repellent skin creams (15%). Compared to a referent group of participants unexposed to mosquito control products, there was no significant association between breast cancer risk and mosquito coils. There was an association in breast cancer risk with reported use of insecticide-treated nets; however, that association was weak and not statistically significant. Participants who reported using repellent sprays were at elevated risks compared to women who did not use any mosquito control products, even after adjustment for all other mosquito control products (OR = 1.42, 95% CI=1.15-1.75). We had limited power to detect an association with repellent skin creams. Although only a few participants reported using repellent room sprays weekly/daily or < month-monthly, no trends were evident with increased frequency of use of repellent sprays, and there was no statistical evidence of heterogeneity by estrogen receptor (ER) status (p-het > 0.25). Our analysis was limited when determining if an association existed with repellent skin creams; therefore, we cannot conclude an association. We found limited evidence of risk associations with widely used mosquito coils and insecticide-treated nets, which are reassuring given their importance for malaria prevention. Our findings regarding specific breast cancer risk associations, specifically those observed between repellent sprays, require further study.

Measured body size and serum estrogen metabolism in postmenopausal women: the Ghana Breast Health Study.

BACKGROUND: Several anthropometric measures have been associated with hormone-related cancers, and it has been shown that estrogen metabolism in postmenopausal women plays an important role in these relationships. However, little is known about circulating estrogen levels in African women, and the relevance to breast cancer or breast cancer risk factors. To shed further light on the relationship of anthropometric factors and estrogen levels in African women, we examined whether measured body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported body size were associated with serum estrogens/estrogen metabolites in a cross-sectional analysis among postmenopausal population-based controls of the Ghana Breast Health Study. METHODS: Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry in serum samples collected from postmenopausal female controls enrolled in the Ghana Breast Health Study, a population-based case-control study conducted in Accra and Kumasi. Geometric means (GMs) of estrogens/estrogen metabolites were estimated using linear regression, adjusting for potential confounders. RESULTS: Measured BMI (≥ 30 vs. 18.5-24.9 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM for unconjugated estrone: 78.90 (66.57-93.53) vs. 50.89 (43.47-59.59), p-value < 0.0001; and unconjugated estradiol: 27.83 (21.47-36.07) vs. 13.26 (10.37-16.95), p-value < 0.0001). Independent of unconjugated estradiol, measured BMI was associated with lower levels of 2-pathway metabolites and higher levels of 16-ketoestradriol. Similar patterns of association were found with WHR; however, the associations were not entirely independent of BMI. Height was not associated with postmenopausal estrogens/estrogen metabolite levels in African women. CONCLUSIONS: We observed strong associations between measured BMI and parent estrogens and estrogen metabolite patterns that largely mirrored relations that have previously been associated with higher breast cancer risk in postmenopausal White women. The consistency of the BMI-estrogen metabolism associations in our study with those previously noted among White women suggests that estrogens likely explain part of the BMI-postmenopausal breast cancer risk in both groups. These findings merit evaluation in Black women, including prospective studies.

The oral microbiome and breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in the Ghana Breast Health Study.

The oral microbiome, like the fecal microbiome, may be related to breast cancer risk. Therefore, we investigated whether the oral microbiome was associated with breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in a case-control study in Ghana. A total of 881 women were included (369 breast cancers, 93 nonmalignant cases and 419 population-based controls). The V4 region of the 16S rRNA gene was sequenced from oral and fecal samples. Alpha-diversity (observed amplicon sequence variants [ASVs], Shannon index and Faith's Phylogenetic Diversity) and beta-diversity (Bray-Curtis, Jaccard and weighted and unweighted UniFrac) metrics were computed. MiRKAT and logistic regression models were used to investigate the case-control associations. Oral sample alpha-diversity was inversely associated with breast cancer and nonmalignant breast disease with odds ratios (95% CIs) per every 10 observed ASVs of 0.86 (0.83-0.89) and 0.79 (0.73-0.85), respectively, compared to controls. Beta-diversity was also associated with breast cancer and nonmalignant breast disease compared to controls (P ≤ .001). The relative abundances of Porphyromonas and Fusobacterium were lower for breast cancer cases compared to controls. Alpha-diversity and presence/relative abundance of specific genera from the oral and fecal microbiome were strongly correlated among breast cancer cases, but weakly correlated among controls. Particularly, the relative abundance of oral Porphyromonas was strongly, inversely correlated with fecal Bacteroides among breast cancer cases (r = -.37, P ≤ .001). Many oral microbial metrics were strongly associated with breast cancer and nonmalignant breast disease, and strongly correlated with fecal microbiome among breast cancer cases, but not controls.

Unmet Needs in Oncology Clinical Research and Treatment in Africa: Focus on Ghana.

Cancer incidence is increasing worldwide and is a major cause of mortality. The relative magnitude of the increase is remarkably high in low human development index (HDI; 95%) and medium HDI (64%) countries. On the African continent, a corresponding increase in cancer burden is predicted, particularly for sub-Saharan Africa. Current epidemiologic data indicate that mortality rates of certain cancers, such as breast and cervical cancers, in sub-Saharan Africa are the highest in the world, and the cancer risks are broadly comparable to the risks in high-income countries, such as the United States and Europe. Although emerging data alludes to the unique genetic profile of cancer in African populations, most cancer therapies are introduced to Africa without confirmatory clinical trials. Therefore, there is an increasing need for clinical trials directed toward prevention, screening, diagnosis, and identification of innovative treatments in the African context. This review will discuss the increasing cancer burden in Africa, with a particular focus on Ghana, unmet clinical needs in cancer, current medical systems, clinical trial regulatory systems, and challenges to clinical trial recruitment.

Associations of fecal microbial profiles with breast cancer and nonmalignant breast disease in the Ghana Breast Health Study.

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray-Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; Ptrend < .001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen-conjugating and immune-related functions were strongly associated with breast cancer (all Ps < .001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially-mediated mechanisms of breast disease.

Reproductive factors and risk of breast cancer by tumor subtypes among Ghanaian women: A population-based case-control study.

Higher proportions of early-onset and estrogen receptor (ER) negative cancers are observed in women of African ancestry than in women of European ancestry. Differences in risk factor distributions and associations by age at diagnosis and ER status may explain this disparity. We analyzed data from 1,126 cases (aged 18-74 years) with invasive breast cancer and 2,106 controls recruited from a population-based case-control study in Ghana. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for menstrual and reproductive factors using polytomous logistic regression models adjusted for potential confounders. Among controls, medians for age at menarche, parity, age at first birth, and breastfeeding/pregnancy were 15 years, 4 births, 20 years and 18 months, respectively. For women ≥50 years, parity and extended breastfeeding were associated with decreased risks: >5 births vs. nulliparous, OR 0.40 (95% CI 0.20-0.83) and 0.71 (95% CI 0.51-0.98) for ≥19 vs. <13 breastfeeding months/pregnancy, which did not differ by ER. In contrast, for earlier onset cases (<50 years) parity was associated with increased risk for ER-negative tumors (p-heterogeneity by ER = 0.02), which was offset by extended breastfeeding. Similar associations were observed by intrinsic-like subtypes. Less consistent relationships were observed with ages at menarche and first birth. Reproductive risk factor distributions are different from European populations but exhibited etiologic heterogeneity by age at diagnosis and ER status similar to other populations. Differences in reproductive patterns and subtype heterogeneity are consistent with racial disparities in subtype distributions.

Health system strengthening: Integration of breast cancer care for improved outcomes.

The adoption of the goal of universal health coverage and the growing burden of cancer in low- and middle-income countries makes it important to consider how to provide cancer care. Specific interventions can strengthen health systems while providing cancer care within a resource-stratified perspective (similar to the World Health Organization-tiered approach). Four specific topics are discussed: essential medicines/essential diagnostics lists; national cancer plans; provision of affordable essential public services (either at no cost to users or through national health insurance); and finally, how a nascent breast cancer program can build on existing programs. A case study of Zambia (a country with a core level of resources for cancer care, using the Breast Health Global Initiative typology) shows how a breast cancer program was built on a cervical cancer program, which in turn had evolved from the HIV/AIDS program. A case study of Brazil (which has enhanced resources for cancer care) describes how access to breast cancer care evolved as universal health coverage expanded. A case study of Uruguay shows how breast cancer outcomes improved as the country shifted from a largely private system to a single-payer national health insurance system in the transition to becoming a country with maximal resources for cancer care. The final case study describes an exciting initiative, the City Cancer Challenge, and how that may lead to improved cancer services.

Hereditary Susceptibility for Triple Negative Breast Cancer Associated With Western Sub-Saharan African Ancestry: Results From an International Surgical Breast Cancer Collaborative.

OBJECTIVE: To investigate subtype-specific risk of germline alleles associated with triple negative breast cancer (TNBC) in African ancestry populations. BACKGROUND: Breast cancer (BC) mortality is higher in African American (AA) compared to White American (WA) women; this disparity is partly explained by 2-fold higher TNBC incidence. METHODS: We used a surgically maintained biospecimen cohort of 2884 BC cases. Subsets of the total (760 AA; 962 WA; 910 West African/Ghanaian; 252 East African/Ethiopian) were analyzed for genotypes of candidate alleles. A subset of 417 healthy controls were also genotyped, to measure associations with overall BC risk and TNBC. RESULTS: TNBC frequency was highest in Ghanaian and AA cases (49% and 44% respectively; P < 0.0001) and lowest in Ethiopian and WA cases (17% and 24% respectively; P < 0.0001). TNBC cases had higher West African ancestry than non-TNBC (P < 0.0001). Frequency of the Duffy-null allele (rs2814778; an African ancestral variant adopted under selective pressure as protection against malaria) was associated with TNBC-specific risk (P < 0.0001), quantified West African Ancestry (P < 0.0001) and was more common in AA, Ghanaians, and TNBC cases. Additionally, rs4849887 was significantly associated with overall BC risk, and both rs2363956 and rs13000023 were associated with TNBC-specific risk, although none as strongly as the Duffy-null variant. CONCLUSIONS: West African ancestry is strongly correlated with TNBC status, as well as germline variants related to BC risk. The Duffy-null allele was associated with TNBC risk in our cohort.

Malignant tumours in urban Ghana: evidence from the city of Kumasi.

BACKGROUND: Data from population-based cancer registries (PBCRs) are a useful resource for estimating the incidence of cancers. PBCR data is useful in the planning and implementation of cancer prevention and control strategies. Ghana's plan for control of non-communicable diseases recognises the need for good quality data to facilitate the attainment of set goals. METHODS: We reviewed data from the Kumasi Cancer Registry for the year 2015. Data collected included clinical and demographic information, laboratory reports and source of case information. Data was entered into the Canreg-5 software. Data was initially analysed using Canreg-5 to estimate the incidence and age standardised rates (ASR) for various tumours. Data was also exported to Microsoft Excel for further analysis using Epi Info version 7.1.4. Microsoft Excel was used to generate charts and graphs. Aggregated data for the years 2013 and 2014 were also analysed for trends in cancer incidence and ASR. RESULTS: A total of 736 cancer cases were recorded among the residents of Kumasi for the year 2015. Females accounted for 62.4% of all cases. The overall incidence of cancer in Kumasi for 2015 was 46.1 per 100,000. The mean age of all cases was 51.3 years (with a range of 1 to 99 years). The incidence among female residents was estimated at 54.1 per 100,000 compared with 37.1 per 100,000 in males. Among females, breast and cervical cancers recorded the highest incidences of 16.1 per 100,000 and 13.7 per 100,000 respectively. Among males, prostate cancer had the highest incidence of 10.5 per 100,000. Breast, cervical and liver cancers were the commonest in both sexes accounting for 19.7, 14.7 and 11.4% of cases respectively. CONCLUSION: There has been significant improvement in data quality and coverage since the inception of our PBCR in 2012. PBCRs are feasible; therefore there is the need for more such registries to improve data on cancers in Ghana. Consistent with other evidence, we found breast cancer as the commonest female cancer in Ghana.

Skin lighteners and hair relaxers as risk factors for breast cancer: results from the Ghana breast health study.

Skin lighteners and hair relaxers, both common among women of African descent, have been suggested as possibly affecting breast cancer risk. In Accra and Kumasi, Ghana, we collected detailed information on usage patterns of both exposures among 1131 invasive breast cancer cases and 2106 population controls. Multivariate analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for breast cancer risk factors. Control usage was 25.8% for ever use of skin lighteners and 90.0% for use of hair relaxers for >1 year. The OR for skin lighteners was 1.10 (95% CI 0.93-1.32), with higher risks for former (1.21, 0.98-1.50) than current (0.96, 0.74-1.24) users. No significant dose-response relations were seen by duration, age at first use or frequency of use. In contrast, an OR of 1.58 (95% CI 1.15-2.18) was associated with use of hair relaxers, with higher risks for former (2.22, 1.56-3.16) than current (1.39, 1.00-1.93) users. Although numbers of burns were inconsistently related to risk, associations increased with duration of use, restricted to women who predominately used non-lye products (P for trend < 0.01). This was most pronounced among women with few children and those with smaller tumors, suggesting a possible role for other unmeasured lifestyle factors. This study does not implicate a substantial role for skin lighteners as breast cancer risk factors, but the findings regarding hair relaxers were less reassuring. The effects of skin lighteners and hair relaxers on breast cancer should continue to be monitored, especially given some biologic plausibility for their affecting risk.

Design considerations for identifying breast cancer risk factors in a population-based study in Africa.

Although breast cancer is becoming more prevalent in Africa, few epidemiologic studies have been undertaken and appropriate methodologic approaches remain uncertain. We therefore conducted a population-based case-control study in Accra and Kumasi, Ghana, enrolling 2,202 women with lesions suspicious for breast cancer and 2,161 population controls. Biopsy tissue for cases prior to neoadjuvant therapy (if given), blood, saliva and fecal samples were sought for study subjects. Response rates, risk factor prevalences and odds ratios for established breast cancer risk factors were calculated. A total of 54.5% of the recruited cases were diagnosed with malignancies, 36.0% with benign conditions and 9.5% with indeterminate diagnoses. Response rates to interviews were 99.2% in cases and 91.9% in controls, with the vast majority of interviewed subjects providing saliva (97.9% in cases vs. 98.8% in controls) and blood (91.8% vs. 82.5%) samples; lower proportions (58.1% vs. 46.1%) provided fecal samples. While risk factor prevalences were unique as compared to women in other countries (e.g., less education, higher parity), cancer risk factors resembled patterns identified elsewhere (elevated risks associated with higher levels of education, familial histories of breast cancer, low parity and larger body sizes). Subjects with benign conditions were younger and exhibited higher socioeconomic profiles (e.g., higher education and lower parity) than those with malignancies, suggesting selective referral influences. While further defining breast cancer risk factors in Africa, this study showed that successful population-based interdisciplinary studies of cancer in Africa are possible but require close attention to diagnostic referral biases and standardized and documented approaches for high-quality data collection, including biospecimens.

Factors contributing to delays in diagnosis of breast cancers in Ghana, West Africa.

BACKGROUND: Late diagnoses and poor prognoses of breast cancer are common throughout Africa. METHODS: To identify responsible factors, we utilized data from a population-based case-control study involving 1184 women with breast malignancies conducted in three hospitals in Accra and Kumasi, Ghana. Interviews focused on potential breast cancer risk factors as well as factors that might contribute to presentation delays. We calculated odds ratios (OR) and 95% confidence intervals (CI) comparing malignances with biopsy masses larger than 5 cm. (62.4% of the 1027 cases with measurable lesions) to smaller lesions. RESULTS: In multivariate analyses, strong predictors of larger masses were limited education (OR 1.96, 95% CI 1.32-2.90

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition.

BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. FUNDING: Bill & Melinda Gates Foundation.

Comparative Analysis of Breast Cancer Phenotypes in African American, White American, and West Versus East African patients: Correlation Between African Ancestry and Triple-Negative Breast Cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC) is more common among African American (AA) and western sub-Saharan African breast cancer (BC) patients compared with White/Caucasian Americans (WA) and Europeans. Little is known about TNBC in east Africa. METHODS: Invasive BC diagnosed 1998-2014 were evaluated: WA and AA patients from the Henry Ford Health System in Detroit, Michigan; Ghanaian/west Africans from the Komfo Anokye Teaching Hospital in Kumasi, Ghana; and Ethiopian/east Africans from the St. Paul's Hospital Millennium Medical College in Addis Ababa, Ethiopia. Histopathology and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), and HER2/neu expression was performed in Michigan on formalin-fixed, paraffin-embedded samples from all cases. RESULTS: A total of 234 Ghanaian (mean age 49 years), 94 Ethiopian (mean age 43 years), 272 AA (mean age 60 years), and 321 WA (mean age 62 years; p = 0.001) patients were compared. ER-negative and TNBC were more common among Ghanaian and AA compared with WA and Ethiopian cases (frequency ER-negativity 71.1 and 37.1 % vs. 19.8 and 28.6 % respectively, p < 0.0001; frequency TNBC 53.2 and 29.8 % vs. 15.5 and 15.0 %, respectively, p < 0.0001). Among patients younger than 50 years, prevalence of TNBC remained highest among Ghanaians (50.8 %) and AA (34.3 %) compared with WA and Ethiopians (approximately 16 % in each; p = 0.0002). CONCLUSIONS: This study confirms an association between TNBC and West African ancestry; TNBC frequency among AA patients is intermediate between WA and Ghanaian/West Africans consistent with genetic admixture following the west Africa-based trans-Atlantic slave trade. TNBC frequency was low among Ethiopians/East Africans; this may reflect less shared ancestry between AA and Ethiopians.

Global surgical oncology disease burden: addressing disparities via global surgery initiatives: the University of Michigan International Breast Cancer Registry.

BACKGROUND: Disparities in breast cancer incidence and outcome between African American and white American women are multifactorial in etiology. The increased frequency of triple-negative breast cancers (TNBC) in African American patients suggests the possible contribution of hereditary factors related to African ancestry. METHODS: The University of Michigan (UM)-Komfo Anoyke Teaching Hospital (KATH) Breast Cancer Research Collaborative and International Breast Registry was established in 2004. It features epidemiologic information, tumor tissue, and germline DNA specimens from African American, white American, and Ghanaian women. RESULTS: This research collaborative has generated valuable findings regarding the pathogenesis and patterns of TNBC while concomitantly improving the standard of breast oncology care in Ghana. This partnership has also yielded important opportunities for academic and educational exchange. It has expanded to involve other sites in Africa and Haiti. CONCLUSIONS: The UM-KATH collaborative is a model for demonstrating the research and academic exchange value of international partnerships.

Characterizing Breast Cancer in a Population with Increased Prevalence of Triple-Negative Breast Cancer: Androgen Receptor and ALDH1 Expression in Ghanaian Women.

BACKGROUND: The androgen receptor (AR) is a commonly-expressed hormone receptor in breast cancer and may be a marker of response to targeted anti-androgen therapy, a particularly attractive option for triple-negative breast cancer (TNBC). Gene expression studies suggest that ARs may distinguish a luminal/AR TNBC subtype from stem cell-like subtypes. TNBC frequency is two to three times higher in African American and African breast cancers compared with White American and European breast cancers, yet little is known regarding TNBC subtypes in high-frequency African-ancestry populations. We evaluated ARs and the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) among breast cancers from Ghana, Africa. METHODS: Overall, 147 formalin-fixed, paraffin-embedded invasive breast cancers from the Komfo Anoyke Teaching Hospital in Ghana were studied at the University of Michigan, and analyzed immunohistochemically for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, ALDH1, and AR expression. RESULTS: The median age of patients was 45 years. Only 31 cases (21 %) were ER-positive, and 14 (10 %) were HER2-positive; 89 (61 %) were TNBCs. For the entire group, 44 % were AR-positive and 45 % were ALDH1-positive. ER/PR-positive tumors were more likely to be AR-positive compared with ER/PR-negative tumors (87 vs. 26 %; p < 0.0001), but there was no association between ALDH1 and AR expression. Among the TNBC cases, 45 % were ALDH1-positive and 24 % were AR-positive. ALDH1 positivity was associated with AR positivity within the subset of TNBC (36 vs. 14 %; p = 0.019). CONCLUSION: We confirmed other studies showing a high frequency of TNBC in Africa. Surprisingly, ALDH1 was found to correlate with AR expression among TNBC, suggesting that novel TNBC subtypes may exist among populations with African ancestry.

Breast cancer in Sub-Saharan Africa: opportunities for prevention.

Although breast cancer is a growing health problem in sub-Saharan Africa, reasons for its increased occurrence remain unclear. We reviewed the published literature to determine the magnitude of the increase in breast cancer, associated risk factors (including for breast cancer subtypes), and ways to reduce incidence and mortality. Some of the increased breast cancer occurrence likely reflects that women are living longer and adopting lifestyles that favor higher incidence rates. However, a greater proportion of breast cancers occur among premenopausal women as compared to elsewhere, which may reflect unique risk factors. Breast cancers diagnosed among African women reportedly include a disproportionate number of poor prognosis tumors, including hormone receptor negative, triple negative, and core basal phenotype tumors. However, it is unclear how lack of standardized methods for tissue collection, fixation, and classification contribute to these rates. Given appropriate classifications, it will be of interest to compare rates with other populations and to identify risk factors that relate to specific tumor subtypes. This includes not only risk factors that have been recognized in other populations but also some that may play unique roles among African women, such as genetic factors, microbiomata, xenoestrogens, hair relaxers, and skin lighteners. With limited opportunities for effective treatment, a focus is needed on identifying etiologic factors that may be amenable to intervention. It will also be essential to understand reasons why women delay seeking care after the onset of symptoms and for there to be educational campaigns about the importance of early detection.

Cancer incidence in Ghana, 2012: evidence from a population-based cancer registry.

BACKGROUND: Data on cancers is a challenge in most developing countries. Population-based cancer registries are also not common in developing countries despite the usefulness of such registries in informing cancer prevention and control programmes. The availability of population-based data on cancers in Africa varies across different countries. In Ghana, data and research on cancer have focussed on specific cancers and have been hospital-based with no reference population. The Kumasi Cancer Registry was established as the first population-based cancer registry in Ghana in 2012 to provide information on cancer cases seen in the city of Kumasi. METHODS: This paper reviews data from the Kumasi Cancer Registry for the year 2012. The reference geographic area for the registry is the city of Kumasi as designated by the 2010 Ghana Population and Housing Census. Data was from all clinical departments of the Komfo Anokye Teaching Hospital, Pathology Laboratory Results, Death Certificates and the Kumasi South Regional Hospital. Data was abstracted and entered into Canreg 5 database. Analysis was conducted using Canreg 5, Microsoft Excel and Epi Info Version 7.1.2.0. RESULTS: The majority of cancers were recorded among females accounting for 69.6% of all cases. The mean age at diagnosis for all cases was 51.6 years. Among males, the mean age at diagnosis was 48.4 compared with 53.0 years for females. The commonest cancers among males were cancers of the Liver (21.1%), Prostate (13.2%), Lung (5.3%) and Stomach (5.3%). Among females, the commonest cancers were cancers of the Breast (33.9%), Cervix (29.4%), Ovary (11.3%) and Endometrium (4.5%). Histology of the primary tumour was the basis of diagnosis in 74% of cases with clinical and other investigations accounting for 17% and 9% respectively. The estimated cancer incidence Age Adjusted Standardised Rate for males was 10.9/100,000 and 22.4/100, 000 for females. CONCLUSION: This first attempt at population-based cancer registration in Ghana indicates that such registries are feasible in resource limited settings as ours. Strengthening Public Health Surveillance and establishing more Population-based Cancer Registries will help improve data quality and national efforts at cancer prevention and control in Ghana.

Fourteen-year experience of a tertiary hospital transfusion committee in West Africa.

BACKGROUND: Hospital transfusion committees (HTCs) have been established in the United States to link producers and users as well as to ensure appropriate use of blood. The HTC has been little reported in sub-Saharan Africa (SSA), although it has been established in some hospitals. STUDY DESIGN AND METHODS: The minutes of three to four HTC meetings per year in a tertiary hospital hosting its own blood service have been reviewed to examine the HTC role over a period of 14 years. Minutes were broken down into themes and indexes, and incomplete data were reinforced by other information sources. Specific data on progress over time were reviewed. RESULTS: The HTC systematically scrutinized the blood supply, blood safety, donor care, clinical use of blood products, and costs. It operated more as a blood transfusion service supervisory board than the limited function allocated to western HTCs. Clinicians and hospital administration were directly involved in decision making and directing investigations to support potential changes and advances in the role and function of the blood transfusion service. The close relation with a UK major blood center and university laboratory provided the impetus and support for research and investigations preliminary to decision making. Data collected and analyzed were reported in the international literature and contributed to disseminate progress made. CONCLUSIONS: The HTC in a major SSA tertiary hospital inclusive of all sections of hospital organization was critically instrumental in decision making, funding, and implementing measures improving the amount and quality of blood products on the basis of evidence collected despite lack of resources. Steps are taken to ensure sustainability of the HTC.

Hormone receptors and Her2 expression in breast cancer in sub-Saharan Africa. A comparative study of biopsies from Ghana and Norway.

Hormonal treatment of breast cancer is effective only in patients whose tumors express estrogen and/or progesterone receptors (ER, PR). Receptor assessment is often not available in low-resource areas, and the choice may be to apply endocrine therapy to all or none of breast cancer patients, depending on the proportion of patients that can be expected to respond. Fifty-one invasive breast cancers from Ghana and 100 from Norway diagnosed in the same laboratory during the same time period were reexamined in a blinded slide review. Of Ghanaian tumors, 76% were ER+ (≥1% ER+ tumor cells). Of Norwegian tumors, 85% were ER+. Triple-negative tumors were seen in 22% of Ghanaian patients and in 7% of Norwegian patients. A review of previous similar studies in sub-Saharan patients shows very discrepant results. Standardization and quality control of receptor assessment and well-designed clinical trials in sub-Saharan African breast cancer patients are needed to give a sound basis for endocrine treatment in this area.