Abiodun Popoola

Prevalence and correlates of depressive disorders in outpatients with breast cancer in Lagos, Nigeria

While the physical complications of breast cancer are often recognized and well managed, the psychological sequelae, especially depression are often unrecognized by healthcare providers and therefore under treated. This study aimed to assess the rate and correlate of depressive disorders in breast cancer survivors in Lagos, Nigeria.

Developing National Cancer Registration in Developing Countries - Case Study of the Nigerian National System of Cancer Registries.

The epidemiological transition in sub-Saharan Africa (SSA) has given rise to a concomitant increase in the incidence of non-communicable diseases including cancers. Worldwide, cancer registries have been shown to be critical for the determination of cancer burden, conduct of research, and in the planning and implementation of cancer control measures. Cancer registration though vital is often neglected in SSA owing to competing demands for resources for healthcare. We report the implementation of a system for representative nation-wide cancer registration in Nigeria – the Nigerian National System of Cancer Registries (NSCR). The NSCR coordinates the activities of cancer registries in Nigeria, strengthens existing registries, establishes new registries, complies and analyses data, and makes these freely available to researchers and policy makers. We highlight the key challenges encountered in implementing this strategy and how they were overcome. This report serves as a guide for other low- and middle-income countries (LMIC) wishing to expand cancer registration coverage in their countries and highlights the training, mentoring, scientific and logistic support, and advocacy that are crucial to sustaining cancer registration programs in LMIC.

Radiation therapy: A major factor in the five-year survival analysis of women with breast cancer in Lagos, Nigeria

PURPOSE This retrospective study was carried out to examine five-year survival from breast cancer cases diagnosed between 2005 and May 2008 in Nigerian women. MATERIAL AND METHODS Two hundred and twenty-four patients were entered into the study. Five-year survival was evaluated using proportional hazard model proposed by Cox to assess variables such as age of diagnosis, menopausal status, and stage of the disease in the two treatment groups: surgery/chemotherapy or surgery/chemotherapy/radiotherapy. RESULTS Findings revealed that the different staging of disease and treatment are independent predictors of disease outcome whereas age of diagnosis and menopausal status although associated with low hazards, are not significant. TNM Stage I (Hazard Ratio=0.153, 95% CI 0.45-0.51, P=0.003), II (Hazard Ratio=0.245, 95% CI 0.12-0.46, P=0.0001), and III (Hazard Ratio=0.449, 95% CI 0.31-0.46, P=0.0001) showed significantly greater survival rates compared to TNM Stage IV for patients receiving surgery/chemotherapy. Similarly, for patients receiving surgery/chemotherapy/radiotherapy TNM Stage II (Hazard Ratio=0.110, 95% CI 0.02-0.46, P=0.003) and III (Hazard Ratio=0.238, 95% CI 0.07-0.73, P=0.012) also showed significantly greater survival rates compared to TNM Stage IV. Treatment had a significant impact on survival independent of stage, age, and menopausal status. Patients receiving surgery/chemotherapy/radiotherapy had a significant increase in survival outcome for TNM Stage (II, P=0.045; III, P=0.0001); age groups (40-49, P=0.021; 50-59, P=0.016; 60-69, P=0.017; >70, P=0.025); and menopausal status (premenopausal, P=0.049; postmenopausal, P=0.0001) compared to those receiving surgery/chemotherapy. CONCLUSION The five-year breast cancer survival rate in Lagos, Nigeria 24.1% (54/224) is relatively poor compared to most countries in the world and needs to be improved. Poor survival rates are mainly attributed to late presentation and poor follow-up, hence early detection through breast cancer awareness programs, appropriate logistics and better management of patients through guidelines for the treatment of breast need to be implemented to improve survival.

Breast Cancer among Urban Nigerian Women: Appraising Presentation and the Quality of Care

Breast Cancer among Urban Nigerian Women: Appraising Presentation and the Quality of Care Introduction: Late presentation is the hallmark of breast cancer among Nigerians. Awareness of the disease is low and care of this condition has not received adequate attention from Government. Health education to improve awareness was intensified in the last 2 decades. This study aims to assess the current state of care and presentation of breast cancer in Lagos, Nigeria. Patients and Methods: A prospective study of 350 breast cancer patients seen over a period of four years at a General Surgical unit out-patient clinic of LASUTH was carried out. Data on patient characteristics, presentation, diagnosis and treatment were obtained and analyzed. Results: Average duration of symptoms was 46.48 weeks. One fifth presented within 3 months while 17% presented after 1 year. Lumps were self-detected in 96% and 287 (82%) presented with advanced disease (stages III & IV). Two hundred and thirty seven patients (67%) received treatment and 175 (74%) among them had mastectomy. None had breast conservation surgery. One hundred and fourteen patients (48%) absconded and did complete treatment. Conclusion: The trend of late presentation has not changed with current efforts to improve breast cancer awareness. Quality of care for our breast cancer patients is not satisfactory and needs improvement.

Role of Private Enterprise in Cancer Control in Low to Middle Income Countries

Background. About 65% of cancer deaths globally occur in low to middle income countries (LMICs) where prioritization and allocation of resources to cancer care are often quite poor. In the absence of governmental focus on this problem, public-private partnerships may be an avenue to provide effective cancer control. Methods. This manuscript highlights the establishment of a nongovernmental organization (NGO) to stimulate the development of partnerships between oncology professionals, private enterprise, and academic institutions, both locally and internationally. Examples of capacity building, grant support, establishment of collaborative networks, and the development of a facility to provide clinical care are highlighted. Results. Collaborations were established between oncology professionals at academic institutions in the US and Nigeria. Cancer control workshops were conducted in Nigeria with grant support from the Union for International Cancer Control (UICC). A monthly tumor board conference was established at LASUTH in Lagos, and further capacity building is underway with grant support from the United States NCI. An outpatient, privately funded oncology clinic in Lagos has been launched. Conclusion. In LMICs, effective partnership between public and private institutions can lead to tangible strides in cancer control. The use of creative healthcare financing models can also support positive change.

Breast cancer receptor status assessment and clinicopathological association in Nigerian women: A retrospective analysis

Background: Breast cancer markers are becoming increasingly important in breast cancer research due to their impact on prognosis, treatment and survival. The present retrospective study was carried out to quantify the proportion of estrogen (ER), progesterone (PR), and human epithelial receptor 2 (HER2) expressions and their association with tumour grade, age, and tumour size in breast cancer patients in Nigeria. Materials and methods: The paraffin embedded tissue sections were analysed for breast cancer markers using monoclonal antibody SP1 for ER and SP2 for PR and polyclonal antibody ErbB2 for HER2. Results: A total of 286 breast cancer paraffin wax tissue sections were analysed for ER, PR and HER2 expression. Of all the tissue samples examined, 20 (7%) were ERpositive, 6 (2.1%) were PR-positive, 11 (3.8%) were HER2-positive whereas 248 (87%) were triple-negative breast carcinoma. ER- and PR-positivity was associated with early grade I and II tumours (P  0.010-0.009) and tumour sizes of  50mm (p  0.001). HER2positivity was positively (P  0.009) associated with grade II tumours and negatively (P  0.0001) associated with grade III tumours. Triple-negative breast cancer was associated with grade III tumours (P  0.0001) and larger tumour sizes of  50mm (P  0.0001). Conclusion: A small proportion of Nigerian women with breast cancer are ER/PR-positive which are associated with less aggressive, better prognosis and benefit from endocrine therapy. An even smaller proportion of patients with aggressive tumors were HER2posivite but responsive to Herceptin treatment. Unfortunately, a very high proportion of cases were triple-negative which is associated with very aggressive tumours and no targeted treatment, which may explain the high mortality rates from breast cancer in Nigeria.

Clinico-Pathological Presentation of Colorectal Cancer Seen in Lagos State University Teaching Hospital

Abstract Aim: The objective is to describe the age and gender distribution, pattern of presentation, sites of colorectal cancers and the histological types of colorectal cancers seen over a 5 year period in a tertiary health institution (Lagos State University Teaching Hospital, Nigeria). Design: A collected data of 104 patients with colorectal cancer from 2006 to 2011 formed the basis of this study. Results: Sixty-five were males and thirty-nine female out of 104 colorectal cases. Age range was between 19 and 78 years. The male female ratio was 1.3:1. 28.8% (30) of the patients presented with stage IV, 46.1 (48) presented with stage III, and 24% (25) presented with stage II. The commonest histological type was adenocarcinoma (84.2%), 46.4% of which were well differentiated. 14.3% had no grade stated. The most common clinical features were suggestive of intestinal obstruction (vomiting & abdominal pain). Conclusion: Most patients in our study presented with late stage disease and this trend especially in this part of the world frequently result in high morbidity and mortality. Policies that promote Public Health education, screening programme which will lead to early diagnosis affordable and effective treatment should be considered.

Abstract PD8-05: Comparative analysis of the genomic landscape of breast cancers from women of African and European ancestry

Objectives: Paucity of data on populations of African Ancestry in clinical trials continues to limit our ability to design and implement innovative solutions to narrow the breast cancer survival gap amongst Africans, African Americans, and European Americans. We have developed a cross-continent research infrastructure to examine the spectrum of genomic alterations in breast tumors from West Africa and subsequently, to compare them to tumors from African American women and women of European Ancestry in The Cancer Genome Atlas (TCGA) database. Methods: Consecutive women with breast cancer presenting for treatment at the University College Hospital, Ibadan and at Lagos State University Teaching Hospital, Lagos, Nigeria gave informed consent and were recruited to the West African Breast Cancer Study (WABCS) between 2013-2016. Tumor-normal pairs were subjected to exome and/or high-depth (90x) genome sequencing. High confidence somatic mutations (substitutions, insertions/deletions and structural variants) were obtained by using multiple variant callers. Furthermore, 1,089 exomic and 80 genomic breast tumor-normal pairs from TCGA were harmonized with WABCS samples, resulting in a cohort of 147 West Africans (147 exome; 40 genome), 154 African Americans (154 exome; 31 genome), and 776 Caucasians (776 exome; 43 genome). Results: Across the exomes, genes commonly altered in breast cancer in TCGA are also altered in women of African ancestry, but the mutational spectrum is quite different, demonstrating overrepresentation of tumors with aggressive phenotypes. Overall, TP53 (65%), ERBB2 (27%), and GATA3 (17%) showed statistically significant higher alteration frequencies in West Africans and African Americans. In contrast, PIK3CA (24%) was less frequently mutated. Of note, GATA3 mutation was statistically significantly more frequent in Nigerians (39%) and African Americans (16.7%) compared to Caucasians (10.5%), in ER-positive cancers. Analysis on Structural Variants (SV), on the other hand, has shown that the genome-wide SV counts among three populations are comparable in ER-negative cancers, while Nigerians have significantly more SV counts compared to African Americans (P=0.0013) or European Americans (P=2.9x10-5) in ER-positive cancers. Similarly, genome-wide substitution patterns in ER+ and ER- cancers varied widely by race/ethnicity. In ER- cases, West Africans carried the highest proportion of canonical APOBEC-associated substitutions, particularly C>T transitions. Conversely, European Americans with ER+ disease showed a higher proportion of C>T than both West Africans (Welch t-test P = 0.044) and African Americans (Welch t-test P = 0.011). Mutation signature analyses highlighted multiple APOBEC signatures, with notable contribution differences across ancestry and ER status. A signature likely corresponding to DNA damage repair correlated with the proportion of genetic ancestry, being most prevalent in European Americans and least common in Nigerians, particularly in ER-negative cancers, with African Americans showing a degree of this signature9s contribution in between the two populations (linear model adjusted for age, P=1.0x10-10). Conclusions: Overall, our data suggests mutation spectra differences in across race/ethnicity and geography. Identification of molecular characteristics such as higher rates of HER2 enriched tumors and higher rates of GATA3 mutations in ER positive tumors are beginning to reveal the genomic basis of race-associated phenotypes and outcomes in breast cancer. Population differences in frequency and spectrum of mutations should now inform the design of innovative clinical trials that improve health equity and accelerate Precision Oncology care in diverse populations. Citation Format: Olopade OI, Pitt JJ, Riester M, Odetunde A, Yoshimatsu T, Labrot E, Ademola A, Sanni A, Okedere B, Mahan S, Nwosu I, Leary R, Ajani M, Johnson RS, Sveen E, Zheng Y, Wang S, Fitzgerald DJ, Grundstad J, Tuteja J, Clayton W, Khramtsova G, Oludara M, Omodele F, Benson O, Adeoye A, Morhason-Bello O, Ogundiran T, Babalola C, Popoola A, Morrissey M, Chen L, Huo D, Falusi A, Winckler W, Obafunwa J, Papoutsakis D, Ojengbede O, White KP, Ibrahim N, Oluwasola O, Barretina J. Comparative analysis of the genomic landscape of breast cancers from women of African and European ancestry [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD8-05.

Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features

Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 − tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation—indicating aggressive biology. GATA3 mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with PIK3CA and CDH1 mutations, which are underrepresented in Nigerians and Blacks. PLK2, KDM6A, and B2M are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations.Research on racial and ethnic influence on breast cancer mortality is stymied by a lack of genomic studies in diverse populations. Here, the authors genomically interrogate 194 Nigerian breast cancers, unveiling molecular features that could explain the high mortality rate from breast cancer in an indigenous African population.

Abstract 1215: Epidemiology of breast malignancies in sub-Saharan Africa: A ten-year retrospective evaluation of 2,419 patients at a major tertiary institution in Southwestern Nigeria

Background: There is limited information on the epidemiology and clinical presentation of breast cancer in Sub-Saharan Africa. This analysis evaluated the prevalence, characteristics of the disease over a ten-year period, as well as the impact of sociodemographic factors on late breast cancer presentation in Lagos State University Teaching Hospital (LASUTH) Lagos, a major tertiary institution in Nigeria, the most populous country in Africa. Objectives: The aim of this study is to determine the epidemiological variants of all breast cancer cases at LASUTH, 2007- 2017. Materials and Methods: There was no restriction on gender or age groups. Late presentation was defined by symptomatic presentation. Tumors were characterized by histological subtypes. Mean, frequencies and percentages were performed using STATA/IC 12.1 for Windows. Results: A total of 2419 breast cancer patients were seen during the ten-year period. There were more female malignancies (n=2380, 98.4%) compared to male malignancies (n=39, 1.6%). The prevalence of breast cancer was found to be 37.5%. The overall mean age (years) was 47.27, the age range was 19 to 91 years. Increased risk of late presentation (n=1910, 79%). Overall higher presentation were made from christians (n= 1849, 76.4%), married individuals (n=2089, 86.4%), people in unskilled professions such as traders (n=808, 33.4%) and people with a tertiary level of education (n= 239, 12.8%). As the primary level of treatment, most of the patients had mastectomy (n=1533, 63.4%), chemotherapy (n=600, 24.8%) and radiotherapy (n=51, 2.1%). The topography of all reported cases include upper-outer quadrant of breast (n=433, 17.9%), axillary tail of breast (n=381, 15.8%), overlying lesion of breast (n=144, 11.5%), lower-inner quadrant of breast (n=133, 5.5%), upper-inner quadrant of breast (n=92, 3.8%), nipple (n=77, 3.2%), lower-outer quadrant of breast (n= 75, 3.1%) and the central portion of breast (n= 42, 1.7%). The three most common morphologies were Pleomorphic carcinoma (n=717, 29.6%), Infiltrating duct carcinoma (n=630, 26%) and giant cell type of the malignant tumor (322, 13.3%). Conclusion: Our study shows that breast cancers usually present mostly in young women in Nigeria, and shows the influence of culture on late presentation. Therefore we should institute deliberate public health education and counseling in our social institutions such as religious circles that are designed particularly to favour the peculiar demographics of the population to prevent late presentation. In addition, cross-sectional studies of breast cancer tumors in younger women (before the age of 40) should be explored to better understand the disease and further understanding too of breast cancers in African American women. Citation Format: Funlayo O. Buraimoh, Abiodun O. Popoola. Epidemiology of breast malignancies in sub-Saharan Africa: A ten-year retrospective evaluation of 2,419 patients at a major tertiary institution in Southwestern Nigeria [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1215.