Breast cancer on the African continent, and in Nigeria especially, is notable for being biologically distinct from those predominantly diagnosed among White populations in the United States and Europe, where most scientific research has occurred to date.
Dr. Tomi Akinyemiju at Duke University School of Medicine examines the factors that contribute to especially aggressive breast cancers in Nigeria – providing insights that could meaningfully impact disease prevention and treatment.
Read the original paper here: https://doi.org/10.1016/j.clbc.2021.11.004.
Image credit: Michael Jung/Shutterstock
Hello and welcome to Research Pod. Thank you for joining us today.
Today we will be diving into research conducted by Dr. Tomi Akinyemiju, Associate Professor in Population Health Sciences at Duke University School of Medicine. Her work examines the factors that contribute to especially aggressive breast cancers in Nigeria – providing insights that could meaningfully impact the prevention and treatment of this devastating illness for so many women.
Breast cancer is the most common cancer globally among women, with over 2 million cases and 0.6 million deaths in 2018. On the African continent, breast cancer rates have been rising, with estimates suggesting a threefold increase in the last few decades. This rise is particularly worrisome because the African continent has the highest age-standardized breast cancer mortality rate globally. Nigeria, the most populous African nation, experiences the highest mortality rate within the continent.
But breast cancer on the African continent and in Nigeria is notable beyond these alarming incidence and mortality rates. These cancers are biologically distinct from those predominantly diagnosed among White populations in the United States and Europe, where most scientific research has occurred to date.
First, the vast majority of breast cancer cases in Nigeria, up to 70%, are diagnosed in the premenopausal years, when women are between the ages of 20 and 50 years. Second, over 50% of the cases in Nigeria are diagnosed at advanced stages with fast-growing, high-grade tumours. Third, breast cancers in Nigerian women are disproportionately classified as the triple-negative subtype. This means that they lack receptors for oestrogen, progesterone, and human epidermal growth factor, making them difficult to target with drugs and thus producing poor clinical outcomes. Strikingly, many of these features of breast cancer in Nigeria parallel those observed among Black women in the United States, suggesting that a better understanding of these aggressive cancers could have implications far beyond women in Nigeria.
This leads us to two key questions – what are the risk factors for these distinctly aggressive breast cancers among women in Nigeria, and Black women in the United States? And, perhaps more importantly, what can be done to prevent these cancers from developing in the first place?
Dr. Akinyemiju is tackling these questions in her study titled the Mechanisms for Novel and Established Risk Factors for Breast Cancer in Women of Nigerian Descent, or simply, MEND. The MEND study was designed as a case-control study, meaning that it’s comprised of patients with newly diagnosed breast cancer, the “cases”, in addition to healthy community-based women, the “controls.” Breast cancer patients were recruited from four hospital sites in southwestern Nigeria.
After providing informed consent, participants in the study completed a comprehensive questionnaire covering their sociodemographic characteristics and medical history, and provided blood and cancer biopsy samples for the study. Information and samples from healthy controls were obtained from the Human Heredity and Health Africa Chronic Kidney Disease Case-Control Study, which overlapped temporally and spatially with the recruitment of breast cancer cases. The MEND study comprises the first contemporary cohort of breast cancer cases and healthy controls in Nigeria.
By developing statistical models to evaluate differences between the cases and controls, Dr. Akinyemiju and her team have identified key risk factors for breast cancer among Nigerian women. Importantly, they have evaluated these risk factors in relation to the most aggressive subtype of breast cancer, the triple-negative subtype, that is seen disproportionately within this population. Their research has focused on lifestyle risk factors that are easily assessed in healthcare settings – such as obesity, elevated cholesterol, inflammation, and metabolic health – and that may therefore have important clinical and public health implications for interventions to address the rising breast cancer burden in Nigeria.
Metabolic syndrome refers to a cluster of connected conditions that include central obesity, insulin resistance, hypertension, and abnormal lipid levels or dyslipidaemia, defined by high triglycerides or low HDL cholesterol. Metabolic syndrome is an established risk factor for cardiovascular disease, stroke, and Type 2 diabetes, and is increasingly being evaluated as a predictor of breast cancer incidence and aggressive tumour biology. Importantly, concurrent with rising breast cancer incidence rates, the prevalence of metabolic syndrome is also rapidly increasing in Nigeria. Estimates of its prevalence range from 12% in rural areas to 35% to 43% in urban areas, and 65% to 85% among adults with type 2 diabetes.
When Dr. Akinyemiju and her team evaluated metabolic syndrome in the MEND study, they found a higher prevalence of metabolic syndrome among breast cancer cases than healthy controls. The presence of metabolic syndrome was associated with almost twofold increased odds of breast cancer. When they stratified by BMI, this association persisted among women who were normal weight, but not among those who were overweight or obese. Strikingly, when they looked at breast cancer subtypes, they found that metabolic syndrome was associated with over fourfold increased odds of triple negative breast cancer, while associations for other subtypes were not significant.
Dr. Akinyemiju’s team has also investigated the individual components of metabolic syndrome in relation to breast cancer in Nigeria. They found that an increase in triglycerides was associated with 1.5-fold increased odds of breast cancer. Among post-menopausal women specifically, higher total cholesterol, LDL cholesterol, and triglycerides were all associated with increased odds of breast cancer. In the analysis of molecular subtypes, clinically low HDL cholesterol was associated with almost threefold increased odds of the aggressive triple-negative subtype.
However, when they evaluated the association between BMI and breast cancer, they found that each unit standard deviation increase in BMI was actually associated with 20% reduced odds of breast cancer. Although similar associations were observed among both premenopausal and postmenopausal women, these associations only achieved statistical significance among premenopausal women. However, among postmenopausal women, higher BMI was associated with 45% reduced odds of the triple-negative subtype. The authors hypothesise that these inverse associations may be consequence of dramatic weight loss experienced by those patients with the most aggressive disease.
The researchers further investigated systemic inflammation in relation to breast cancer using C-reactive protein or CRP levels in the blood. They found that the cases were significantly more likely to have high CRP levels. CRP in the highest tertile was associated with a statistically significant fourfold increased odds of breast cancer. They also found that CRP in the highest tertile was associated with threefold increased odds of the aggressive triple-negative breast cancer subtype.
In conclusion, research led by Dr. Akinyemiju uniquely probes the risk factors associated with breast cancer in Nigeria. Ultimately, her team’s findings suggest that aggressive public health and clinical interventions targeting metabolic syndrome and inflammation, such as those addressing diet, physical activity, treatment for diabetes, abnormal cholesterol levels, and inflammation, may provide immediate benefits in reducing the future risk of aggressive breast cancer among Nigerian women.
This research was made possible through support from the National Institutes of Health, National Cancer Institute, and Fogarty International Center. Dr. Akinyemiju and her team thank the many MEND investigators who contributed to the development of this study, the patients and families who participated in the MEND study, and the countless staff members, nurses, and doctors who have played an instrumental role in accomplishing the study goals.
Thank you so much for listening in today. Be sure to check out the original MEND research papers published by Dr. Akinyemiju and her team, linked in the notes for this episode, and stay subscribed to Research Pod for all the latest in research news. See you again soon.