**Abstract**

Breast cancer has increasingly become a disease of high morbidity and mortality globally, and in the sub-Saharan African region in particular. Therefore, there is a need to review the current status of breast cancer in the region in the last decade. Though Africa has one of the lowest incidence rates, it has the highest mortality rate globally. There have been reported inter- and intra-country variations in breast cancer morbidity and mortality in the region, with East Africa having the largest incidence rate increase, while southern Africa experiences the lowest increase between 2008 and 2012. Histology remains the commonest modality of diagnosis in sub-Saharan Africa; with invasive ductal cancers being the commonest among patients. Novel genes have also been popular among certain populations, in the presence of the more popular BRACA genes. Adverse outcomes reported include physical and mental health outcomes, which have been linked to some health behaviours. There has been varying modalities of treatments across the region. Therefore, there is a need for better organized and improved screening/diagnostics service accessibility in resourceconstrained settings in sub-Saharan Africa. There should also be increased awareness creation among African populations about the availability of treatment facilities and modalities in their communities.

**Keywords:** breast cancer, morbidity, mortality, incidence, adverse outcomes, novel genes, sub-Saharan Africa

## **1. Introduction**

Breast cancer is the most common cancer among women and one of the most important causes of death among them. Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide with 2.3 million new cases in 2020 and the fifth leading cause of cancer mortality, with 685,000 deaths [1, 2]. It ranks first for incidence in the vast majority of countries (159 of 185 countries) and mortality in 110 countries, and it accounts for 11.7% of all incident cancer cases – just ahead of new lung cancer cases [2]. It is the leading cause of cancer-related morbidity and mortality among women; accounting for 24.5% of all incident cancer cases and 15.5% of cancer-related mortality [2]. Incidence rates are 88% higher in transitioned countries than in transitioning countries (55.9 and 29.7 per 100,000, respectively), with the highest incidence rates (>80 per 100,000) in Australia/New Zealand, Western Europe (Belgium has the world's highest incidence), Northern America, and Northern Europe and the lowest rates (<40 per 100,000) in Central America, Eastern and Middle Africa, and South-Central Asia [1, 2]. High and very high HDI countries have 55.9 incidence ASR per 100,000 females compared to 29.7 incidence ASR per 100,000 females globally [2]. Furthermore, China has the highest proportion of incident cases of breast cancer, globally; accounting for 49.3%, 49.9%, and 48.6% of total incidence rates overall, males and females, respectively [2]. The burden of breast cancer has been projected to reach over 3 million incident cases and 1 million deaths every year by the year 2040 [1].

Generally, the global burden of breast cancer is reported to be an age-standardized incidence rate of 43.3 per 100,000 women per year and an age-standardized mortality rate of 12.9 per 100,000 women per year. The more developed countries significantly have a higher incidence rate (74.1 per 100, 000 women per year) and mortality rate (14.9 per 100,000 women per year) compared to the less developed countries with an incidence rate of 31.3 per 100,000 women per year and mortality rate of 11.5 per 100,000 women per year [3]. High and very high HDI countries have a 12.8 mortality ASR per 100,000 females compared to a 15.0 mortality ASR per 100,000 females globally [2]. While Western Europe has the highest incidence of breast cancer (90.7 incidence ASR per 100,000 women); the West African region and Melanesia have the highest mortality (22.3 and 27.5 ASR per 100,000 women, respectively) [2]. Furthermore, China has the highest proportion of breast cancer-related mortality rates, globally; accounting for 58.3%, 60.6%, and 55.5% of total mortality rates overall, males and females, respectively [2].

Incidence rates of breast cancer are rising fast in transitioning countries in South America, Africa, and Asia as well as in high-income Asian countries where rates are historically low [2]. Dramatic changes in lifestyle, sociocultural, and built environments brought about by growing economies and an increase in the proportion of women in the industrial workforce have had an impact on the prevalence of breast cancer risk factors—the postponement of childbearing and having fewer children, greater levels of excess body weight and physical inactivity—and have resulted in a convergence toward the risk factor profile of western countries and narrowing international gaps in breast cancer morbidity [4].

Incidence and death rates have increased over the last three decades due to longstanding higher reproductive and hormonal risk factor profiles (such as early age at menarche, later age, at menopause, advanced age at first birth, fewer number of children, less breastfeeding, menopausal hormone therapy, oral contraceptives, diethylstilbestrol), behavioral risk factors (alcohol intake, smoking, excess body weight, physical inactivity, insufficient vitamin supplementation, intake of processed food, excessive exposure to artificial light, exposure to chemicals and other drugs), higher prevalence of breast cancer-associated genes, better cancer registration, and cancer detection [4–7]. The non-modifiable factors include female sex, older age, family history, ethnicity/race, genetic mutation, pregnancy and breastfeeding, menstrual period and menopause, the density of breast tissue, previous history of breast cancer, noncancerous breast diseases and previous radiation therapy [7]. The incidence rate of breast cancer varies greatly with race and ethnicity and is higher in developed countries [2, 4, 6].

Literature has shown that the mortality rate of breast cancer is higher in less developed regions [2, 6]. women living in transitioning countries have 17% higher mortality rates compared with women in transitioned countries (15.0 and 12.8 per 100,000, respectively) because of high fatality rates, with the highest mortality

rates found in Melanesia, Western Africa, Micronesia/Polynesia, and the Caribbean (Barbados has the world's highest mortality) [2]. A 5 -year survival variation analysis for breast cancer has now been said to be close to 90% in the US and Australia; while as low as 40% in South Africa according to a CONCORD-3 study of cancer survival in 71 countries [8].

There is thus a need to review the epidemiology of breast cancer in the last decade; examine gaps and proffer recommendations to aid the prevention and control of breast cancer in sub-Saharan Africa.

#### **1.1 The burden of breast cancer in sub-Saharan Africa**

Breast cancer is the leading diagnosed cancer and the second most common cause of cancer mortality in sub-Saharan Africa. Sub-Saharan Africa has the highest agestandardized incidence rate of 17.3 per 100,000 women per year, globally; with the Southern Africa region and West African region having the highest age-standardized incidence rate of 38.9 and 38.6 per 100,000 women per year in sub-Saharan Africa, respectively. However, the Northern Africa region has the highest incidence rate of 43.2 ASR incidence in the whole of Africa [3]. Country-specific prevalence shows that there is a 15.3%, 4.6% and 3.3% prevalence of breast cancer in the Central African Republic, Rwanda and Sierra Leone, respectively [9, 10]. Mauritius and Nigeria have been said to be the countries with the highest incidence in Africa at 64.2 and 50.4 ASR incidence per 100,000 repetitively [3].

The 5-year age-standardized relative survival in 12 sub-Saharan African countries was 66% for cases diagnosed during 2008 through 2015, sharply contrasting with 85% to 90% for cases diagnosed in high-income countries from 2010 through 2014 [8]. A multi-country estimate of 3-year survival of breast cancer patients was 50% [95%CI: 48, 53] between 2014 and 2017 [11]. Western African region has the highest mortality rate of 20.1 ASR mortality per 100,000; with central African region having the least mortality rate of 14.9 ASR mortality globally. However, Nigeria has the highest mortality rate in Africa with 25.9 ASR mortality per 100,000 [3]. This is, nonetheless, higher than the world average of 12.9 ASR mortality [3].

Population-specific variations in 3-year mortality rates have also been reported across sub-Saharan Africa; with a survival range of 90% among white women to 56% in black Namibian women; and in South Africa where survival ranges from 76% among mixed-race women to 59% in black women [11]. Country-specific variation in 3-year mortality shows a 44–47% survival rate in Uganda and Zambia compared to the 36% survival rate in Nigeria [11].

The population-specific 5-year survival ASR was as low as 5% [95%CI: 1.9, 11.3] in Uganda (Kyadondo) and as high as 80% [95%CI: 22.2, 96.8] and 93.7% [95%CI: 75.5, 98.5] in Namibia and Mauritius, respectively [12]; comparable to 55% in the US state of Connecticut and 57% in Norway during the late 1940s, 48 3 decades before the introduction of mammography screening and modern therapies [2]. Survival also varies within countries in sub-Saharan Africa. For example, in Zimbabwe 3-year relative survival rate in the capital (Harare) is 56.7% [95%CI: 48.2, 64.6] compared to 21.6% [95%CI: 8.2, 39.8] reported in Bulawayo [12].

These variations can be said to be due to the level of access to early diagnosis and prompt treatment of breast cancer cases across the continent; with up to 22% survival increase in Nigeria, Uganda and Zambia [11]. Further explanation for the variations between countries may also be a result of their level of human development index (HDI). For example, though Mauritius (a country with a very high HDI) has the highest incidence rate of breast cancer in Africa [3]; it also has the highest survival rate compared to Zimbabwe (medium HDI) with a lower survival rate [12]. This shows that though, Mauritius detects more breast cancer patients; most of whom were able to survive beyond the 5-year survival period – which can be due to improved access to prompt diagnosis and early treatment for a better outcome.

Because organized, population-based mammography screening programs may not be cost-effective or feasible in low-resource settings [13], efforts to promote early detection through improved breast cancer awareness and clinical breast examination by skilled health providers [14], followed by timely and appropriate treatment, are essential components to improving survival. A recent study conducted in 5 sub-Saharan African countries estimated that 28% to 37% of breast cancer deaths in these countries could be prevented through an early diagnosis of symptomatic disease and adequate treatment, with a fairly equal contribution of each [11]. The Breast Health Global Initiative has established a series of evidence-based, resource-stratified guidelines that support phased implementation into real-world practice [15].
