This is a large study looking at 2,418 breast cancer samples of Ghanaians with samples collected across the country. Breast cancer predominantly affects women. The prevalence of breast cancer in Ghana was 21.5% (10,134 cases) in 2020 with prevalence of EOBC in same year being 15.2%.[1] In the current study, the prevalence of EOBC is 20.2%, a figure higher than the recorded prevalence of EOBC in 2020 but lower than a previously reported rate of 30% in one report.[1] Male patients younger than 40 years in the study population accounted for 1.8% as opposed 1.2% in LOBC. In a similar but prospective study in UK involving 2956 women aged between 18 to 40 years, the median age determined was 36 years, which is slightly higher than what we found in our study, 34.66 years.[6]
Similar to previous publications, we identified Invasive Carcinoma NST as the commonest cancer type both in the EOBC and LOBC.[7–9] However, the proportion was lower among the younger patients (85.20%) compared to the older patients (88.50%) in our cohort. Presence of DCIS component was higher in EOBCs (4.50% vs 2.60%). The occurrence of special types of carcinomas such as lobular carcinoma and mucinous carcinoma was just a fraction higher in EOBC patients compared to their LOBC (3.7% and 3.10%) as against (2.20% and 2.70%) respectively. These findings differ from that of studies by Andrikopoulou et al. who found a similar trend but higher rates in younger patients than in older patients.[4]
In sub-Saharan Africa, breast cancer has been reported to be more aggressive, and of higher grade than breast cancer diagnosed in developed countries[10]. Similarly, in the current study, the percentage of grade III tumours (47.30%) was the same in both EOBC and LOBC. The Ki 67 score was however higher in the EOBC. This conforms with literature that EOBCs express higher levels of the cellular proliferation associated antigen Ki-67 in line with their aggressiveness.[11–13]
There was no significant difference in lymphovascular invasion status between both age categories. There was a more than two-fold chance that there was perineural invasion by cancers in older patients (LOBCs) when compared with EOBCs (3.6% vs 1.60%). This was statistically significant and may be due to the larger number of late onset cancers in our cohort. The relationship between ageing, breast density and susceptibility to perineural invasion in the event of cancer needs more attention.[14]
In relation to stage, although majority of cases in both age groups were late stage many more (27.30%) EOBCs were larger, with size > 5.0cm compared to 21.7% in the older persons group. Again, more EOBCs presented with carcinoma-in-situ with invasive tumour (10.50% vs 4.30%) Majority of EOBCs were thus at least pT2 (36.80%) vs 34.80% in the LOBC. In relation to lymph nodes, 13.80% of EOBCs were staged as pN3 compared to 9.0% of late onset cases. Further analysis showed that majority of late onset cancers presented with no lymph node involvement (36.10%) compared with 34.50% in the EOBC. A larger frequency of positive lymph nodes (65.50% vs 63.00%) was recorded in EOBCs than in the older persons with a significant proportion being pN3 suggesting a higher stage at presentation of EOBCs compared to LOBCs although these findings are not statistically significant. In line with our findings, previous publications have reported larger tumours in younger patients with increased nodal involvement.[6, 11] This could be attributed to the fact that, women under the age of 35 do not typically undergo breast cancer screening unless they are at high risk of developing breast cancer. The sensitivity of a mammogram is equally low in this population due to increased density of the breast, which obscures findings on mammogram.[15]
The molecular subtypes used in this study are based on the recommended definition by the 13th St Gallen International Breast Cancer Conference (2013) Expert Panel review defining Luminal A as (ER and PR positive, HER2 negative, Ki-67 low), Luminal B (HER2 negative) (ER-positive, HER negative and at least one of Ki-67 high or PR negative), Luminal B (HER2 positive) (ER-positive, HER2 positive and any of Ki-67 high or PR positive), HER2-enriched (HER2 positive, ER-negative, PR negative) and Triple Negative Breast Cancer (TNBC) (ER-negative, PR negative, HER2 negative). The panel also set the threshold of ≥ 20% as indicative of high Ki-67.[14] Analysis of hormonal status indicates EOBCs in our setting more often tend to be hormone receptor (HR) negative when compared with LOBCs (47.70% vs 44.30%) contrary to the findings of Adrikopoulou et al.[4] in Greece who obtained 21.9% HR negative status among young women compared to 30.0% in the older women.[4]
Intrinsic Molecular subtypes of breast cancer in the current study are dominated by TNBCs among EOBCs when compared to LOBCs (26.40% against 24.30%). TNBC is however equally the most frequent molecular subtype in both age groups. Luminal A was also slightly more frequent in EOBC than in the older persons (11.30 vs 10.80%). Luminal B with HER2 Positive frequencies were the same with both recording 9.40% while Luminal B with HER2 Negative was more frequent in the older persons than in EOBC (22.10% vs 19.20%). HER2-enriched was higher in older persons than in EOBC in the study population (11.70% vs 11.10%). Elsewhere, a study by Collins et al.[16] analysed the different subtypes of breast cancer in 399 women aged < 40 years identified 35% Luminal B tumours, 33% Luminal A tumours, 11% HER2 enriched tumours, and 21% TNBCs. Another study by Anders et al.[17, 18] evaluated gene expression profiles and identified 17% of tumours to be Luminal A. Luminal B was 27% and HER2 enriched was 22% with Basal-like tumours forming 34% of their cohort. Proportions in our study are closer to those found by Anders et al. with Luminal B (Luminal B HER2 + and Luminal B HER2-) forming 28.5% of tumours in our cohort. With some literature quoting prevalence of TNBC to be up to 80%[19] but generally around 53.2% in the Ghanaian population it is likely that these rather high scores are partly a result of false negatives due to poor pre-analytics.[20] Our TNBC rates are lower than reported in the Ghanaian literature although still higher when compared to TNBC rates in other populations. Our finding is likely a result of improved pre-analytics and because all cases were subjected to similar pre-analytical and analytical conditions.