**2. The distribution of breast cancer in sub-Saharan Africa**

Globally, while Africa has one of the lowest age-standardized breast cancer incidence rates (36.2 per 100,000 women per year) after Asia (29.1 per 100,000 women per year); it has the highest mortality rate of 17.3 per 100, 000 compared to other regions of the world. However, the mortality rate is highest (20.1 per 100,000 women per year) in the West African sub-region [3]. Majority of breast cancer patients in sub-Saharan Africa are women [16–18]. A recent systematic review reported that 97% [95%CI: 97–98] of all breast cancer cases in Africa are seen in Females [16]. About 18% prevalence has been reported among male Ethiopians; which is likely the highest in the region among breast cancer patients [16]. Oftentimes, many of these breast cancer rates are obtained from institutional-based records or registries across sub-Saharan Africa; with varying reports across the sub-continent.

More than half (58%) of breast cancer patients were diagnosed before the age of 50 [16]. The median and peak ages have also been reported in some studies. The peak age of incidence of 47.8%, 52.5%, 57.4%, 57.5% and 57.9% between the 3rd and 5 th decades among patients in Rwanda, Lagos-Nigeria, Southern Ethiopia, Central African Republic and Northwest Amhara regions of Ethiopia, respectively [9, 17, 19–21]. Similar report was observed among breast cancer patients in Adis Ababa Ethiopia with 63.1% at the same peak range [22]. Almost two-thirds of breast cancer patients are below 50 years old in Burkina Faso [23]. Gabretsadik A et al, in a seven-year (2013–2019) review, reported a median age of 38 years among patients in Southern Ethiopia [21]. Ouedraogo SY et al, Balekouzou et al. and Sayed et al. reported a mean age of 45.79 years, 45.85 years, 47.5 years and 47.8% among patients with breast cancer in Burkina Faso, Central African Republic, Kenya and Rwanda [9, 18, 19, 23]. Fatiregun reported a mean age of 49.6 (±11.2) years among breast cancer patients in Lagos, Nigeria [20]. However, a population-based study revealed a much lower average age of 33.4 (± 1.25) in Burkina Faso [24]. This shows that institutionalbased studies might present a higher age level compared to the population-based study and give an illusion of higher average age of patties with breast cancer. Thus, studies must indicate the study setting to contextualize the study findings.

It was also observed that the number of cases diagnosed or reported is dependent on the distance of communities from the health facilities offering screening, diagnosis and

treatment. For example, Gabretsadik et al. reported a higher number of cases in zones and districts closest to the tertiary hospital in Hawassa city; with the number of cases observed to thin out as the distance increases away from this specialist University hospital. It can be said that, unless a population-based survey is done, the true incidence/ prevalence and distribution of breast cancer in communities in sub-Saharan Africa may be unknown and estimates from institutions will be affected by Berksonian Bias [21].

#### **2.1 African trends on breast cancer**

Some of the most rapid increases are occurring in sub-Saharan Africa. Between the mid-1990s and the mid-2010s, incidence rates increased by >5% per year in Malawi (Blantyre), Nigeria (Ibadan), and Seychelles and by 3% to 4% per year in South Africa (Eastern Cape and Zimbabwe (Harare) [25]. Between 2008 and 2012, East Africa experienced the largest incidence rate increase of 36.5% from 19.30 ASR in 2008 incidence to 30.4 ASR in 2012. However, the incidence remains highest in the North African region at 43.2 ASR; with southern Africa having the lowest increase of 2% from 38.2 ASR incidence in 2008 to 38.9 ASR incidence in 2012 [3]. In southern Ethiopia, there has been an increasing incidence of breast cancer between 2013 and 2019 according to institutional records. It has increased from 12.3% in 2013 to 19.0% in 2019 [21]. Nigeria has continuously shown increases in incident rates from 13.7 ASR between 1960 and 1969 to 50.4 ASR between 2000 and 2012 and has been projected to 84.2 ASR between 2013 and 2050 [3]. In Central African Republic, the average prevalence rate has been on the increase; with breast cancer prevalence just above 10% in 2003 and just above 15% in 2015 among breast cancer patients; after dropping from 20% in 2014 [9].

Mortality rates in sub-Saharan African regions have increased simultaneously and rank now the world's highest, reflecting weak health infrastructure and subsequently poor survival outcomes. Between the same periods, East Africa also showed the largest increase of 26% mortality from 11.4 ASR in 2008 to 15.6 ASR in 2012. Southern Africa has the least mortality rate reduction of 24.5%; with a reduction from 19.3 ASR mortality in 2008 to 15.5 ASR mortality in 2012 [3]. This has been said to be due to the human development index of the country and stage at diagnosis. For example, low HDI (HR: 2.3 [95%CI: 1.4, 3.7]; p = 0.001) and medium HDI (HR: 1.9 [95%CI: 1.2, 3.1]; p = 0.01) countries are more likely to have higher odds of breast cancer-related mortality compared to African HDI countries. Patients in late stages at presentation have higher odds (HR: 2.5 [95%CI: 1.8, 3.3]; p < 0.001) of breast cancer-related deaths compared to those who presented at the early stage of the disease [12].

#### **2.2 Determinants/risk factors of breast cancer reported in the last decade**

Various factors have been associated with the development of breast malignancies across sub-Saharan Africa in the last decade. Body size has been associated with the development of breast cancer. A recent study from Ghana, by Brighton LA et al, reported that increasing body size increased the likelihood of breast cancer (slightly heavy body size – OR: 1.30 [95%CI: 1.04, 1.62] and heavy body size – OR: 1.50 [95%CI: 1.11, 2.02]) among patients with suspicious lesions of breast cancer [5]. Level of education has also been associated with the development of breast cancer among Populations in the region. The higher the level of education, the higher the likelihood of the development of breast cancer. Also from the same Ghanaian study, those with at least secondary school education (more than basic education) are significantly more likely to develop breast cancer compared to those without formal education.

(OR:1.50 [95%CI: 1.21, 1.87]; p < 0.01) [5]. The number of births has also been said to reduce the likelihood of breast cancer. multiparous women (at least 5 orders) are significantly less likely to develop breast cancer compared to nulliparous Ghanaian patients (parity ≥5 - OR: 0.71 [95%CI: 0.52,0.97]; p < 0.01) [5].
