This is a large study looking at 2418 Ghanaian breast cancer patients from across the country. The International Agency for Research on Cancer (IARC) estimated the number of prevalent cases (5-years) in 2020 to be 10,134, (21.5% of all cancer cases) with an estimated incidence of 4482 (18.7% of all cancers) in the same year . The estimates also suggest that 1147 (19.7% of breast cancers) were diagnosed in patients younger than 40 years (EOBC) with an estimated number of prevalent cases (5-years) of EOBC in the same year being 15.2% . 20.2% of our study population was EOBC which is higher than the IARC’s estimated number of prevalent cases for the same age group over 5-years (15.2%). The figure is however closer to the prevalence of EOBC for one year (18.6%) and for three (3) years (17.1%). Other researchers have reported a rate of 30% of Ghanaian breast cancer patients . Male breast cancer was more frequent in the EOBC compared to LOBC (1.8% vs 1.2%). The median age of patients with EOBC was 34.66 years. This is lower than the 36 years reported for a study of EOBCs in the UK involving 2956 patients . In relation to age, it is documented that breast cancer in women older than 40 years generally occurs at a lower age in Ghanaians [1, 6]. Our findings thus suggest that this is also true for patients younger than 40 years.
Similar to previous reports, Invasive Carcinoma, No Special Type (NST) / Not Otherwise Specified (NOS) was the commonest type of breast cancer in both EOBC and LOBC patients [6,7,8,9]. However, in our cohort, the proportion of Invasive Carcinoma NST/NOS was lower among patients younger than 40 years (85.20%) compared to those 40 years or older (88.50%). Presence of DCIS component was however higher in EOBCs (24.80% vs 21.60%). The occurrence of ‘special types’ of carcinomas such as lobular carcinoma and mucinous carcinoma was just a fraction higher in EOBC compared to 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 higher rate of invasive ductal carcinoma in younger patients than in older patients . They however reported similar findings in relation to the overall frequency of invasive ductal carcinomas compared to other cancers such as lobular carcinoma, thus confirming the general established trend that invasive ductal carcinoma is the commonest type of breast cancer diagnosed among all age groups.
Breast cancer has been reported to be generally more aggressive, and of higher grade in Africans [4, 6, 10]. In line with the established trend, majority of diagnosed cancers were of higher grade. The proportions of grade III tumours (47.30%) was the same in both EOBC and LOBC. Though a slightly higher proportion of Grade I tumours (18.40%) were reported in the EOBC group compared to the LOBC group (15.40%), the Ki 67 score of tumours was higher in the EOBC. This conforms to literature that EOBCs express higher levels of the cellular proliferation associated antigen Ki-67 in line with their aggressiveness [11,12,13].
Though we did not find any 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. Again, the relationship between ageing, breast density and susceptibility to perineural invasion in the event of cancer needs more attention .
In relation to stage, although majority of cases in both age groups were late stage, many more (27.30%) EOBCs were larger, with size > 5.0 cm compared to 21.7% in the LOBC. The general low rate of screening services in Ghana has been cited as a reason for the late presentation of breast cancers. Most screening programs focus on early detection and rely on regular self or health worker breast examination with such services peaking in October of every year. Such screening is even less common in young women who are generally thought not to be at risk for breast cancer . Again, more EOBCs presented with carcinoma-in-situ associated with invasive tumour (10.50% vs 4.30%). In line with the larger size at presentation, 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 also 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 frequency of nodal involvement [6, 7, 11]. This could be attributed to the fact that, women under the age of 35 years do not routinely undergo breast cancer screening unless they are at high risk of developing breast cancer. Again, the sensitivity of a mammogram is equally low in this population due to the increased density of the breast, which obscures findings on mammogram . The general late stage of presentation of our patients in both age groups has been established in the literature in relation to the presentation of breast cancer in Ghana .
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 . Analysis of hormone receptor status indicates that in our setting, EOBCs 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.  in Greece who obtained 21.9% HR negative status among young women compared to 30.0% in the older women .
The Molecular subtypes of breast cancer in the current study are dominated by more TNBCs among EOBCs when compared to LOBCs (26.40% against 24.30%). TNBC is however the most frequent molecular subtype of breast cancer in both age groups. Luminal A breast cancer was also slightly more frequent in EOBC than in the older persons (11.30% vs 10.80%). The proportion of Luminal B with HER-2 Positive cancers was the same with both groups recording 9.40% while Luminal B with HER-2 Negative was more frequent in the older persons (LOBC) than in EOBC (22.10% vs 19.20%). HER-2-enriched cancers were also marginally more frequent in in older persons than in EOBCs in the study population (11.70% vs 11.10%). Elsewhere, a study by Collins et al.  that 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, 27% Luminal B and 22% HER2 enriched cancers. In their study Basal-like tumours formed 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. Our reported TNBC proportion of 26.40% though not including equivocal cases is significantly lower than the proportions reported in many earlier publications. With some literature quoting the percentage of TNBC to be up to 80%  but generally around 53.2% in the Ghanaian population it is likely that these rather high reported proportions are partly a result of false negatives due to poor pre-analytics . Though our TNBC rates are lower than previously reported in the Ghanaian literature, it is still higher when compared to proportions of TNBC in other populations. Our finding is likely a result of improved pre-analytics because all cases were subjected to similar pre-analytical and analytical conditions.