Differences in plasma microRNA content impair microRNA-based signature for breast cancer diagnosis in cohorts recruited from heterogeneous environmental sites.

Circulating microRNAs are non-invasive biomarkers that can be used for breast cancer diagnosis. However, differences in cancer tissue microRNA expression are observed in populations with different genetic/environmental backgrounds. This work aims at checking if a previously identified diagnostic circulating microRNA signature is efficient in other genetic and environmental contexts, and if a universal circulating signature might be possible. Two populations are used: women recruited in Belgium and Rwanda. Breast cancer patients and healthy controls were recruited in both populations (Belgium: 143 primary breast cancers and 136 healthy controls; Rwanda: 82 primary breast cancers and 73 healthy controls; Ntot = 434), and cohorts with matched age and cancer subtypes were compared. Plasmatic microRNA profiling was performed by RT-qPCR. Random Forest was used to (1) evaluate the performances of the previously described breast cancer diagnostic tool identified in Belgian-recruited cohorts on Rwandan-recruited cohorts and vice versa; (2) define new diagnostic signatures common to both recruitment sites; (3) define new diagnostic signatures efficient in the Rwandan population. None of the circulating microRNA signatures identified is accurate enough to be used as a diagnostic test in both populations. However, accurate circulating microRNA signatures can be found for each specific population, when taken separately.

Screening of germline mutations in young Rwandan patients with breast cancers.

BACKGROUND: In Sub-Saharan Africa breast cancer is commonly detected at younger age and the profile is more aggressive with a high mortality rate compared to the European countries. It is suggested that African-specific genetic background plays a key role in this matter. The present study aimed at understanding the role of genetic factors in breast cancer development in young Rwandan. METHODS: We performed a massive parallel sequencing on Illumina MiSeq NGS system for the screening of 26 genes associated with hereditary breast cancer from 40 patients under 35 years old from two University Teaching Hospitals in Kigali, Rwanda. Sanger sequencing was used to confirm pathogenic and likely pathogenic mutations. RESULTS: Five patients out of 40 (12.5%) presented with pathogenic mutations including four patients (10%) carrying BRCA1 or BRCA2 pathogenic variants. One patient showed a missense likely pathogenic TP53 variant. We have also detected additional missense, intronic, and 3'UTR variants of unknown significance in all study participants. CONCLUSION: This preliminary study suggests that the frequency of germline mutations in young Rwandan patients with breast cancer is similar to the observations made in Caucasians. However, further large studies including patients and controls are needed to better understand the impact of genetic factors as well as the environmental risk factors in the development of breast cancer in young Rwandans.

Prevalence of Histological Characteristics of Breast Cancer in Rwanda in Relation to Age and Tumor Stages.

Breast cancer is a complex disease, and it is the most common cause of morbidity and mortality among women worldwide. In Sub-Saharan Africa, the clinical characteristics and tumor profiles of breast cancer are still unknown. In the present study we aimed to determine breast tumor profiles of the Rwandan patients in relation to age and tumor stages. We compare our findings to related results from other sub-Saharan Africa studies. Data on age at diagnosis, tumor stage, and hormonal profiles of 138 patients diagnosed between January 2015 and December 2018 were retrospectively retrieved from electronic medical records at three referral hospitals in Rwanda. We compared our results to related findings reported in other Sub-Saharan African countries. All statistical analyses were done using SPSS Inc., Chicago, IL, USA, version 20 and R software languages. The mean age at diagnosis was 49.7 years (SD = 13) and ranged from 17 to 86 years. The majority of patients (57.2%) were diagnosed before 50 years of age compared with 42.8% aged > 50 years. Tumor stage III was the commonest accounting for 62% followed by stage II with 24.8%. The distribution of breast tumor subtypes was ER-, PR-, HER2-: 37.7%; ER+, PR+, HER2-: 31.2%; ER-, PR-, HER2+: 14.5%; ER+, PR+, HER2+: 5.1%; and other subtypes represented 11.6%. There was no statistically significant difference in age and tumor stages between the molecular subtypes. Our findings revealed the predominance of hormonal negative tumors among Rwandan patients with breast cancer. Triple negative was found to be the most common breast tumor subtype regardless of age and tumor stage. Larger prospective studies could examine genetics and environmental factors that may play a role in the differences of tumor characteristics in Sub-Saharan populations.