Breast cancer in Ethiopia: evidence for geographic difference in the distribution of molecular subtypes in Africa | BMC Women’s Health

KeepHealthCare.ORG – Breast cancer in Ethiopia: evidence for geographic difference in the distribution of molecular subtypes in Africa | BMC Women’s Health

Progress in molecular research have led to the classification of breast cancers into distinct subgroups (luminal, normal breast-like, Her2/neu-positive and basal-like subtypes) based on mRNA expression profiles [25]. However, gene expression profiling using cDNA microarray or RNA seq technology is not currently feasible in clinical settings due to its high cost and technical complexity. Therefore, IHC markers have been validated and used as surrogates for cDNA microarray in molecular subtyping of breast cancer [26].

In the present study, we found that luminal A subtype was the most prevalent followed by luminal B subtype, Triple Negative, and HER2-enriched derived exclusively. Our findings, from TMA IHC, are in contrast to most other studies performed in standard paraffin sections, in tissues from Sub-Saharan Africa particularly in west and central African countries where triple negative phenotype was reported to be the most common molecular subtype (43–82%) of breast cancer [16]. In Europe, North America, Asia and middle eastern countries, 30–70% of breast cancers are luminal A tumors and our result (40%) is comparable to the distribution seen in the western societies [27, 28]. However, Luminal B which is the second most common molecular subtype in our study (26%) is present at higher proportion among our study participants when compared to the rate seen in the Western high resource regions, Asia and middle east (10–20%) [27, 28].

A previous study among Ethiopian women carried out by Kantelhardt [20] in 2014 compared ER negativity in 352 patients out of 1208 consecutive patients treated at Addis Ababa-University Hospital, Ethiopia, from June 2005 through December 2010. They reported ER negative tumors to be around 35% in agreement with our present results [20]. A comparable result was also reported in a recent study done by groups at the University of Michigan in 2016 from one of the referral hospitals in Addis Ababa where they found ER negative tumors to be 26.5% [22].

A study among women of East African origin in US, in which a majority of the subjects (74%) were Ethiopians living in the United States, reported estrogen receptor negative tumors at 22% [

29

]. Similarly, recent studies in Kenya reported estrogen receptor negative tumor at 27.2% [

21

]. These few studies among East Africans, as well as our present study, which are summarized in Table 

6

suggest the existence of geographical diversity in the distribution of molecular subtypes of breast cancer in Sub-Saharan Africa. These findings indicate that the frequency of ER negative tumors in East Africa may not be different from that found in the Western countries which is between 20 to 30% [

15

].

Table 6

Comparison of distribution of Molecular subtypes of Breast Cancer from Selected East African Studies

This Study, Endale et al.

Ethiopia

114

43

35

56

76

23

Jiagge et al., 2016 [22]

Ethiopia

94

43

15

Sayed S et al.,2014 [21]

Kenya

301

47.5

27.2

35.2

82.4a

20.2

Kantelhardt et al., 2014 [20]

Ethiopia

352

35

49

Jemal and Fedewa, 2012 [29]

USAb

186

48

22

35

Similarly the frequencies of triple negative tumors in these East African studies were lower than reported from west and central Africa. TNBC in the Kenyan study was reported in 20.2% of all cases [21] and TNBC in the Michigan study among Ethiopian women was reported to be around 15% which is lower than our finding (23%), but all of these studies indicate TNBC tumors to be less common than reported elsewhere in Africa. Hence, taken together, the data from East Africa suggest that it would not be accurate to associate African ancestry with increased probability of diagnosis with ER negative or TNBC tumors, as the Sub-Saharan African populations are known to be themselves highly heterogeneous in lifestyles, exposures, and genetic admixtures.

Present study has shown HER2 positivity at a slightly lower proportion than the rate seen among Ethiopians in the Michigan study [22] study (33%), the only other study (to our knowledge) which has incorporated HER2 assessment for molecular phenotyping of breast cancer from Ethiopia. However, HER2 positivity in our study (23%) is comparable to white Americans, African Americans, and West Africans which is about 17%, 19% and 20% respectively [22].

Our result shows an earlier onset of luminal B compared to the other molecular subtypes with statistically significant difference in median age at diagnosis (P < 0.05). The median age at diagnosis in our study also reveals a decline in luminal B subtypes as patients’ age increase with the incidence of luminal A exceeding that of luminal B at age ranges > = 50. This finding is comparable to a studies in the west where a bimodal age distribution at diagnosis is seen where incidence of the more aggressive phenotype luminal B peaks at earlier ages whereas luminal A type peaks at older ages [30].

The median age at diagnosis in our study was comparable to most previous studies in Africa and the few studies done among breast cancer patients in Ethiopia [20, 22]. However, it is much lower than the median age at diagnosis in most Western countries which is (55–60 years) [31]. The difference could be explained by the fact that African nations have younger population pyramids and the proportions reported in this and earlier studies are not age adjusted so the distributions are expected to always be shifted to younger ages in African cases compared to the cases in western countries; only 5% of African population is older than 60 years as compared to 24% of the population of Europe [32] being > 60 years old. More extensive population based registries in Africa, with active registration of cases, are urgently needed to understand the burden of cancer and to aid in cancer control program. Gaining a better understanding of environmental and lifestyle risk factors is crucial, as the incidence of breast cancer appears to be increasing at all ages in all African regions.

There was no statistically significant difference between median age at diagnosis and the ER status of breast cancer in this study. In this study, invasive ductal carcinoma was the predominant histological type (60%), which is comparable to the study by Kantelhardt in 2014 [20]. No statistically significant correlation was found between the molecular subtypes of breast cancer and histological type of breast cancer in this study, although the numbers of non ductal histologies were very low in the study. High tumor grade (Grade III) was reported in 34% of our study participants which is comparable with the study done by Kantelhardt [20]. The increased rate of high grade tumors observed in this study is in part possibly due to late diagnosis of breast cancer. No statistically significant correlation was found between the molecular subtypes of breast cancer and tumor grade in this study. The numbers of cases in each category were likely too small to appreciate differences, if they exist.

Limitations of the present study include selection bias which is due to enrollment of participants with available FFPE in the pathology laboratory, missing clinicopathological information and small sample size. Larger studies from population based samples are necessary to help guide cancer control programs. In spite of its stated limitations, our study adds strength to the notion that investments in utilization of hormonal and anti-HER2 therapies have potential to impact survival in Ethiopia, so efforts to spread education about implementing these strategies are recommended in light of the relatively high proportion of tumors amenable to these treatments.

Source: https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-018-0531-2

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