Ernest Adjei

Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women

Breast cancers that are negative for the estrogen receptor (ER), the progesterone receptor (PR), and the HER2 (human epidermal growth factor receptor 2) marker are more prevalent among African women, and the biologically aggressive nature of these triple‐negative breast cancers (TNBCs) may be attributed to their mammary stem cell features. Little is known about expression of the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) in African women. Novel data are reported regarding ALDH1 expression in benign and cancerous breast tissue of Ghanaian women.

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.

Characterizing breast cancer treatment pathways in Kumasi, Ghana from onset of symptoms to final outcome: Outlook towards cancer control

BACKGROUND Cancer rates are increasing in Africa, including Ghana. Breast cancer is the second most common cancer in incidence and mortality in Ghana. OBJECTIVE We outlined both breast cancer patient characteristics and management at the Komfo Anokye Teaching Hospital (KATH), the main cancer management hospital in central Ghana. Moreover, we identified the treatment interventions predictive of patient outcome. METHODS Medical records of 597 breast cancer patients seen in 2008-2011 were abstracted to investigate management and treatment patterns. Abstracted variables included type and extent of surgery, number and cycles of chemotherapy and radiotherapy, as well as the course of treatment completed. RESULTS Late stage at diagnosis was common, treatment plans of the study hospital were relatively standardized according to disease severity, and defaulting/interrupting treatment in the records was also common. Patients diagnosed with late stage cancer who received adjuvant therapy and patients with hormone status evaluation were more likely to have complied with treatment guidelines and continued oncotherapy at the study hospital than those who never had hormone status requested or reported. CONCLUSIONS Our study lends support to improving patient outcomes in low- and middle-income countries through raising knowledge and reporting of tumor hormonal status and providing appropriately tailored treatment. Achieving improved outcomes should also consider enhancing public understanding of the importance of early detection and completion of treatment.

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.

Breast Cancer and African Ancestry: Lessons Learned at the 10-Year Anniversary of the Ghana-Michigan Research Partnership and International Breast Registry

Women with African ancestry in western, sub-Saharan Africa and in the United States represent a population subset facing an increased risk of being diagnosed with biologically aggressive phenotypes of breast cancer that are negative for the estrogen receptor, the progesterone receptor, and the HER2/neu marker. These tumors are commonly referred to as triple-negative breast cancer. Disparities in breast cancer incidence and outcome related to racial or ethnic identity motivated the establishment of the International Breast Registry, on the basis of partnerships between the Komfo Anokye Teaching Hospital in Kumasi, Ghana, the University of Michigan Comprehensive Cancer Center in Ann Arbor, Michigan, and the Henry Ford Health System in Detroit, Michigan. This research collaborative has featured educational training programs as well as scientific investigations related to the comparative biology of breast cancer in Ghanaian African, African American, and white/European American patients. Currently, the International Breast Registry has expanded to include African American patients throughout the United States by partnering with the Sisters Network (a national African American breast cancer survivors’ organization) and additional sites in Ghana (representing West Africa) as well as Ethiopia (representing East Africa). Its activities are now coordinated through the Henry Ford Health System International Center for the Study of Breast Cancer Subtypes. Herein, we review the history and results of this international program at its 10-year anniversary.

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.

Mucin expression patterns in histological grades of colonic cancers in Ghanaian population

Introduction Myriad roles of mucins in normal tissues have been well documented, including lubrication of the epithelial surfaces; protection from physical damage; facilitation in cell-cell signaling and suppression of inflammatory activity. Pathological expression of mucins has been noted in cancer development and progression. This study sought to identify and quantify the types of mucins produced during various histological grades of colon cancer and to assess the diagnostic significance. Methods Formalin fixed, paraffin-embedded tissue blocks, comprising three (3) normal colon and twenty-two (22) colon cancer tissues, were retrieved from the archives of the histopathology department of the Komfo Anokye Teaching Hospital. They were stained with Haematoxylin and eosin (H&E) for diagnosis and grading of tumours. Tissues were pre-digested with diastase and stained with Alcian blue (pH 2.5)/Periodic Acid Schiff to characterize the mucin variants present. Results Our findings indicated that normal colonic tissues expressed exceptionally high amount of acid mucin and low amount of neutral mucin. However, there was a general decrease in mucin expression in colon cancers compared to normal colon tissues. Additional findings suggested that as cancer progresses from low grade to high grade of adenocarcinoma of the colon, there was generally a considerable decrease in the acid mucin production and an increase in the neutral mucin expression. In contrast, a sizeable subpopulation of high-grade adenocarcinomas of colon showed a rather opposite mucin expression pattern- increase in acid mucin and a decrease in neutral mucin. Conclusion As colonic cancer progresses, there are corresponding changes in the mucin types and content such that there are decrease in acid mucin and increase in neutral mucin expressions.

Breast Cancer in Ghana: Demonstrating the Need for Population-Based Cancer Registries in Low- and Middle-Income Countries

Purpose Breast cancer, the most common cancer worldwide, is the leading cause of cancer mortality in Ghanaian women. Previous studies find Ghanaian women are diagnosed at a younger age and at more advanced stages (III and IV), and have tumors with characteristics similar to African American women. We sought to remedy gaps in knowledge about breast cancer survival in Ghana and its relation to demographic and biologic factors of the tumors at diagnosis to assist in cancer control and registration planning. Methods Individuals with a breast cancer diagnosis who sought care at Komfo Anokye Teaching Hospital from 2009 to 2014 were identified via medical records. Follow-up telephone interviews were held to assess survival. Kaplan-Meier plots and Cox proportional hazards models assessed survival associated with clinical and demographic characteristics. Results A total of 223 patients completed follow-up and were analyzed. The median survival was 3.8 years. Approximately 50% of patients were diagnosed with grade 3 tumors, which significantly increased the risk of recurrence or death (hazard ratio [HR] for grade 2 versus 1, 2.98; 95% CI, 1.26 to 7.02; HR grade 3 v 1, 2.56; 95% CI, 1.08 to 6.07; P = .04). No other variables were significantly associated with survival. Conclusion Higher tumor grade was significantly associated with shorter survival, indicating impact of aggressive biology at diagnosis on higher risk of cancer spread and recurrence. Contrary to prevailing notions, telephone numbers were not reliable for follow-up. Collecting additional contact information will likely contribute to improvements in patient care and tracking. A region-wide population-based active registry is important to implement cancer control programs and improve survival in sub-Saharan Africa.

Androgen Receptor and ALDH1 Expression Among Internationally Diverse Patient Populations

Purpose Population-based incidence rates of breast cancers that are negative for estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2/neu (triple-negative breast cancer [TNBC]) are higher among African American (AA) compared with white American (WA) women, and TNBC prevalence is elevated among selected populations of African patients. The extent to which TNBC risk is related to East African versus West African ancestry, and whether these associations extend to expression of other biomarkers, is uncertain. Methods We used immunohistochemistry to evaluate estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2/neu, androgen receptor and aldehyde dehydrogenase 1 (ALDH1) expression among WA (n = 153), AA (n = 76), Ethiopian (Eth)/East African (n = 90), and Ghanaian (Gh)/West African (n = 286) patients with breast cancer through an institutional review board–approved international research program. Results Mean age at diagnosis was 43, 49, 60, and 57 years for the Eth, Gh, AA, and WA patients, respectively. TNBC frequency was higher for AA and Gh patients (41% and 54%, respectively) compared with WA and Eth patients (23% and 15%, respectively; P < .001) Frequency of ALDH1 positivity was higher for AA and Gh patients (32% and 36%, respectively) compared with WA and Eth patients (23% and 17%, respectively; P = .007). Significant differences were observed for distribution of androgen receptor positivity: 71%, 55%, 42%, and 50% for the WA, AA, Gh, and Eth patients, respectively (P = .008). Conclusion Extent of African ancestry seems to be associated with particular breast cancer phenotypes. West African ancestry correlates with increased risk of TNBC and breast cancers that are positive for ALDH1.

Sustainable Development of Pathology in Sub-Saharan Africa: An Example From Ghana

CONTEXT - Pathology services are poorly developed in Sub-Saharan Africa. Komfo Anokye Teaching Hospital in Kumasi, Ghana, asked for help from the pathology department of the University Hospital of North Norway, Tromsø. OBJECTIVE - To reestablish surgical pathology and cytology in an African pathology department in which these functions had ceased completely, and to develop the department into a self-supporting unit of good international standard and with the capacity to train new pathologists. DESIGN - Medical technologists from Kumasi were trained in histotechnology in Norway, they were returned to Kumasi, and they produced histologic slides that were temporarily sent to Norway for diagnosis. Two Ghanaian doctors received pathology training for 4 years in Norway. Mutual visits by pathologists and technologists from the 2 hospitals were arranged for the introduction of immunohistochemistry and cytology. Pathologists from Norway visited Kumasi for 1 month each year during 2007-2010. Microscopes and immunohistochemistry equipment were provided from Norway. Other laboratory equipment and a new building were provided by the Ghanaian hospital. RESULTS - The Ghanaian hospital had a surgical pathology service from the first project year. At 11 years after the start of the project, the services included autopsy, surgical pathology, cytopathology, frozen sections, and limited use of immunohistochemistry, and the department had 10 residents at different levels of training. CONCLUSIONS - A Ghanaian pathology department that performed autopsies only was developed into a self-supported department with surgical pathology, cytology, immunohistochemistry, and frozen section service, with an active residency program and the capacity for further development that is independent from assistance abroad.