References of "JOSSE, Claire"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailDifferences in plasma microRNA content impair microRNA-based signature for breast cancer diagnosis in cohorts recruited from heterogeneous environmental sites.
Uyisenga, Jeanne P. ULiege; Debit, Ahmed ULiege; Poulet, Christophe ULiege et al

in Scientific Reports (2021), 11(1), 11698

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 33 (6 ULiège)
Full Text
Peer Reviewed
See detailHigh plasmatic levels of IL-4 and IL- 13 are associated with recurrence and worse survival in breast cancer
Onesti, Concetta Elisa ULiege; JOSSE, Claire ULiege; Boulet, Delphine ULiege et al

in Tumori Journal (2020, October 31)

Background: The immune system has a role in breast tumor, in particular in triple negative (TNBC) and in hormone receptor-negative/HER2-positive breast cancers. The aim of this study is to analyze the ... [more ▼]

Background: The immune system has a role in breast tumor, in particular in triple negative (TNBC) and in hormone receptor-negative/HER2-positive breast cancers. The aim of this study is to analyze the association between baseline cytokines expression with cancer relapse and outcome. Material and methods: Baseline plasmatic samples of 66 stage I-III breast cancers treated with surgery with or without radiotherapy and systemic treatment between 2011 and 2017 were collected. A panel of 24 cytokines were analyzed by Luminex MAGPIX technology, using multiplex Luminex Magnetic Assay kits (®R&D System). Results: Sixty-six breast cancer patients were included in the study. The median follow-up was of 78 months (range 18-99). The median age at diagnosis was of 58.5 years (range 32-86). The stage at diagnosis was I in 29 (43.9%) patients, II in 26 (39.4%) and III in 11 (16.7%). The histological type was ductal in 47 cases (71.2%), lobular in 13 (19.7%) and mixed in 6 (9.1%). Fifty-three (80.3%) patients were estrogen-receptor-positive, 11 (16.7%) HER2-positive and 12 (18.2%) TNBC. All the patients received surgery, combined with neo/adjuvant chemotherapy in 35 (53%) cases, anti-HER2 in 9 (13.6%), hormonotherapy in 53 (80.3%) and radiotherapy in 52 (78.8%). During the follow-up we observed 11 relapses and 4 deaths. IL-4 was associated with relapse, that occurs in 30.7% of the cases in the group with IL-4 > 0.07 (IL4-H) mean fluorescence intensity (MFI) vs in 7.5% in the group with IL-4 ⩽ 0.07 MFI (IL4-L) (p 0.013), with a ROC curve AUC of 0.745. In multivariate analysis relapse was associated with IL-13 (p 0.048) and T stage (p 0.049). Survival analysis showed a better time to treatment failure (TTF) for the group IL4-L (5y-TTF 87% vs 63% for IL4-L and IL4-H, p 0.022) and for the group with IL-13 ⩽ 0.1 MFI (IL13-L) compared IL-13 > 0.1 MFI (IL13-H) (5y-TTF 90% vs 45%, p 0.017). A separation of the curves was also observed for breast cancer specific survival (5y-BCSS: 95% vs 84% for IL4-L vs IL4-H, p 0.118; 91% vs 75% for IL13-L vs IL13-H, p 0.029). Conclusions: Higher baseline plasmatic level of IL-4 and IL-13 are associated with a worse prognosis in early stage breast cancer. These are two structurally and functionally related cytokines known for regulating the immune system activity, leading to a T helper-2 response and to a macrophage M2 polarization. Data should be confirmed in a larger cohort and a mechanistic study is advisable. [less ▲]

Detailed reference viewed: 36 (7 ULiège)
Full Text
Peer Reviewed
See detailThe relative eosinophil count in breast cancer as an emerging prognostic biomarker
ONESTI, Concetta Elisa ULiege; JOSSE, Claire ULiege; Beaumecker, Barbara ULiege et al

in European Journal of Cancer (2020, October 02)

Background: Cancer outcome appears to be affected by circulating immune cells in several tumor types. The role of peripheral eosinophils was widely studied in melanoma, while less data are available for ... [more ▼]

Background: Cancer outcome appears to be affected by circulating immune cells in several tumor types. The role of peripheral eosinophils was widely studied in melanoma, while less data are available for breast cancer (BC) so far. In a previous study, we showed an association between baseline relative eosinophil count (REC), pathological complete response and survival rate in triple negative and hormone receptor negative/HER2 positive breast cancer. In this retrospective study we analyzed the role of REC in all breast cancer subtypes at time of diagnosis and during follow-up. Material and Methods: Stage I-III BC patients (pts) treated between 1999 and 2018 were included in the study. REC and relative lymphocyte count (RLC) at seven different timepoints were collected. The pts were divided into two groups according to REC, using 1.5% as threshold, and according to RLC, using 17.5% as threshold. The co-primary endpoints were the BC specific survival (BCSS) and the time to treatment failure (TTF) according to REC. The secondary endpoints were: BCSS and TTF according to RLC, the association between REC and RLC with relapse; the variation of REC during follow-up and at relapse. Statistical analysis was done with SPSS v25 software. Results: Overall 930 early BC pts were included in the study. The median age of the whole cohort was 61 years (25–97). The pts were well balanced according to the TNM stage in the group REC-low (393 pts) and in the group REC-high (597 pts): 30.5% and 32.9% stage I; 45.3% and 45.1% stage II; 22.6% and 21.4% stage III respectively; 1.4% unknown. After a median follow-up of 91 months (range 1–245) we observed a benefit in TTF (HR 0.610–95% CI 0.458–0.812, p 0.001) and BCSS (HR 0.632–95%CI 0.433– 0.923, p 0.018) in REC-high vs REC-low group. A survival benefit was observed also in the RLC-high vs RLC-low group (TTF: HR 0.421–95% CI 0.262–0.677, p 0.001; BCSS: HR 0.350–95% CI 0.2–0.614, p 0.001). A lower rate of relapse was observed in the REC-high vs REC-low group (17.1% vs 24.7%, p 0.005) and in the RLC-high vs RLC-low group (19.4% vs 35.8%, p 0.004). We observed a lower median REC at baseline before surgery (1.8% and 1.4% in pts without and with relapse respectively), compared to the median value after surgery (2.7% and 2.5% respectively), that remain stable until 10 years of postsurgical follow up in cancer free pts. A decrease in median REC was detected at time of relapse (1.5%). All the differences observed in the groups of pts with and without tumor recurrence were statistically significant (p < 0.0001), suggesting a role of the presence of cancer in the modulation of eosinophil count. Conclusions: REC could be a new promising, affordable and accessible predictive and prognostic biomarker in all BC subtypes. Mechanistic studies, ongoing in our laboratory, are needed to understand eosinophils’ physiopathological role. [less ▲]

Detailed reference viewed: 35 (5 ULiège)
Full Text
Peer Reviewed
See detailGREB1L variants in familial and sporadic hereditary urogenital adysplasia and Mayer-Rokitansky-Kuster-Hauser syndrome
Jacquinet, Adeline ULiege; Boujemla, Bouchra ULiege; FASQUELLE, Corinne ULiege et al

in Clinical Genetics (2020), 98(2), 126-137

Congenital uterine anomalies (CUA) may have major impacts on the health and social well-being of affected individuals. Their expressivity is variable, with the most severe end of the spectrum being the ... [more ▼]

Congenital uterine anomalies (CUA) may have major impacts on the health and social well-being of affected individuals. Their expressivity is variable, with the most severe end of the spectrum being the absence of any fully or unilaterally developed uterus (aplastic uterus), which is a major feature in Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH). So far, etiologies of CUA remain largely unknown. As reports of familial occurrences argue for strong genetic contributors in some cases, we performed whole exome sequencing in nine multiplex families with recurrence of uterine and kidney malformations, a condition called hereditary urogenital adysplasia. Heterozygous likely causative variants in the gene GREB1L were identified in four of these families, confirming GREB1L as an important gene for proper uterine and kidney development. The apparent mode of inheritance was autosomal dominant with incomplete penetrance. The four families included fetuses with uterovaginal aplasia and bilateral renal agenesis, highlighting the importance to investigate GREB1L in such phenotypes. Subsequent sequencing of the gene in a cohort of 68 individuals with MRKH syndrome or uterine malformation (mostly sporadic cases) identified six additional variants of unknown significance. We therefore conclude that heterozygous GREB1L variants contribute to MRKH syndrome and this probably requires additional genetic or environmental factors for full penetrance. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd [less ▲]

Detailed reference viewed: 29 (3 ULiège)
Full Text
Peer Reviewed
See detailScreening of germline mutations in young Rwandan patients with breast cancers
Uyisenga, Jeanne ULiege; SEGERS, Karin ULiege; Lumaka, A. Z. et al

in Molecular Genetics and Genomic Medicine (2020)

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 ... [more ▼]

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. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. [less ▲]

Detailed reference viewed: 58 (10 ULiège)
Full Text
Peer Reviewed
See detailPrevalence of Histological Characteristics of Breast Cancer in Rwanda in Relation to Age and Tumor Stages
Uyisenga, Jeanne ULiege; Butera, Yvan ULiege; Debit, Ahmed ULiege et al

in Hormones and Cancer (2020)

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 ... [more ▼]

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. © 2020, Springer Science+Business Media, LLC, part of Springer Nature. [less ▲]

Detailed reference viewed: 48 (12 ULiège)
Full Text
Peer Reviewed
See detailBlood eosinophilic relative count is prognostic for breast cancer and associated with the presence of tumor at diagnosis and at time of relapse
ONESTI, Concetta Elisa ULiege; JOSSE, Claire ULiege; Boulet, Delphine ULiege et al

in Oncoimmunology (2020)

Background: Cancer outcome is associated with circulating immune cells, including eosinophils. Here we analyze the relative eosinophil count (REC) in different breast cancer subtypes. Methods: Stage I–III ... [more ▼]

Background: Cancer outcome is associated with circulating immune cells, including eosinophils. Here we analyze the relative eosinophil count (REC) in different breast cancer subtypes. Methods: Stage I–III breast cancer patients were included in the study and classified as REC-high vs low (cutoff 1.5%) or relative lymphocyte count (RLC)-high vs low (cutoff 17.5%). The co-primary endpoints were the breast cancer-specific survival (BCSS) or the time to treatment failure (TTF) in the REC groups. Results: Overall 930 patients were included in the study. We observed a benefit for REC-high vs REC-low in TTF (HR 0.610, 95% CI 0.458–0.812), and in BCSS (HR 0.632, 95% CI 0.433–0.923). Similarly, we observed a better TTF (HR 0.421, 95% CI 0.262–0.677) and BCSS (HR 0.350, 95% CI 0.200–0.614) in RLC-high vs low. A lower relapse rate was observed in the REC-high vs REC-low group (17.1% vs 24.7%, p = 0.005), not confirmed in the multivariate analysis. A lower median REC at baseline and at relapse was observed compared to REC after surgery and during cancer-free follow-up (p < .0001). Conclusions: REC could be a new promising, affordable and accessible predictive and prognostic biomarker in all breast cancer subtypes. [less ▲]

Detailed reference viewed: 44 (15 ULiège)
Full Text
Peer Reviewed
See detailPrimary sarcoma of the breast in the young Rwandan females
Uyisenga, Jeanne ULiege; SEGERS, Karin ULiege; Butera, Yvan ULiege et al

in Breast Cancer Reports (2019), 6(2),

Primary breast sarcoma (PBS) is a very rare disease with an annual incidence estimated to 45 cases per million. It rises from breast connective tissue and constitutes highly recurrent tumors with poor ... [more ▼]

Primary breast sarcoma (PBS) is a very rare disease with an annual incidence estimated to 45 cases per million. It rises from breast connective tissue and constitutes highly recurrent tumors with poor prognosis. The management of the primary breast sarcoma relies on the tumor size, histology, and requires a multidisciplinary approach. In sub-Saharan Africa PBS was very rarely reported. We are reporting here on two cases. The two cases observed in our settings were young women who presented with high-grade sarcoma showing an aggressive form, a very fast recurrence and worse prognosis within few months following the diagnosis. [less ▲]

Detailed reference viewed: 28 (4 ULiège)
Full Text
See detailGermline mutations in young Rwandan with breast cancers
Uyisenga, Jeanne ULiege; SEGERS, Karin ULiege; Lumaka Zola, Aimé ULiege et al

Scientific conference (2019, September 26)

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 European countries. It is suggested that ... [more ▼]

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 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 forty 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 while one patient showing a missense likely pathogenic TP53Varian. 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 investigate the additional genetic factors as well as the impact of the environmental risk factors in the development of breast cancer in young Rwandans. [less ▲]

Detailed reference viewed: 19 (3 ULiège)
Full Text
See detailTOWARDS AN ACCURATE CANCER DIAGNOSIS MODELIZATION:COMPARISON OF RANDOM FOREST STRATEGIES
Debit, Ahmed ULiege; Poulet, Christophe ULiege; JOSSE, Claire ULiege et al

Poster (2019, March 15)

Machine learning approaches are heavily used to produce models that will one day support clinical decisions. To be reliably used as a medical decision, such diagnosis and prognosis tools have to harbor a ... [more ▼]

Machine learning approaches are heavily used to produce models that will one day support clinical decisions. To be reliably used as a medical decision, such diagnosis and prognosis tools have to harbor a high-level of precision. Random Forests have been already used in cancer diagnosis, prognosis, and screening. Numerous Random Forests methods have been derived from the original random forest algorithm from Breiman et al. in 2001. Nevertheless, the precision of their generated models remains unknown when facing biological data. The precision of such models can be therefore too variable to produce models with the same accuracy of classification, making them useless in daily clinics. Here, we perform an empirical comparison of Random Forest based strategies, looking for their precision in model accuracy and overall computational time. An assessment of 15 methods is carried out for the classification of paired normal -tumor patients, from 3 TCGA RNA-Seq datasets: BRCA (Breast Invasive Carcinoma), LUSC (Lung Squamous Cell Carcinoma), and THCA (Thyroid Carcinoma). Results demonstrate noteworthy differences in the precisions of the model accuracy and the overall time processing, between the strategies for one dataset, as well as between datasets for one strategy. Therefore, we highly recommend to test each random forest strategy prior to modelization. This will certainly improve the precision in model accuracy while revealing the method of choice for the candidate data. [less ▲]

Detailed reference viewed: 52 (4 ULiège)
Full Text
Peer Reviewed
See detailTryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy
ONESTI, Concetta Elisa ULiege; BOEMER, François ULiege; JOSSE, Claire ULiege et al

in Journal of Translational Medicine (2019), 17

Background: Indoleamine 2,3-dioxygenase catalyzes the conversion of tryptophan to kynurenine, an immunosuppressive metabolite involved in T regulatory cell differentiation. Indoleamine 2,3-dioxygenase is ... [more ▼]

Background: Indoleamine 2,3-dioxygenase catalyzes the conversion of tryptophan to kynurenine, an immunosuppressive metabolite involved in T regulatory cell differentiation. Indoleamine 2,3-dioxygenase is expressed in many cancer types, including breast cancer. Here, we analyze kynurenine and tryptophan and their ratio in breast cancer patients and healthy controls. Methods: Breast cancer patients and healthy controls were prospectively enrolled in our study. All subjects underwent blood sample withdrawal at diagnosis or on the day of screening mammography for the healthy controls. Plasmatic kynurenine and tryptophan were determined on a TQ5500 tandem mass spectrometer after chromatographic separation. Results: We enrolled 146 healthy controls and 202 women with stages I–III breast cancer of all subtypes. All patients underwent surgery, 126 underwent neoadjuvant chemotherapy with 43 showing a pathological complete response, and 43 underwent adjuvant chemotherapy. We observed significantly higher plasmatic kynurenine, tryptophan and their ratio for the healthy controls compared to patients with breast cancer. We observed a lower plasmatic tryptophan and a higher kynurenine/tryptophan ratio in hormone receptor-negative patients compared to hormone receptor-positive cancers. Lobular cancers showed a lower ratio than any other histologies. Advanced cancers were associated with a lower tryptophan level and higher grades with an increased kynurenine/tryptophan ratio. Pathological complete response was associated with higher kynurenine values. The plasmatic kynurenine, tryptophan and kynurenine/tryptophan ratios were not predictive of survival. Conclusions: The plasmatic kynurenine, tryptophan and kynurenine/tryptophan ratio could differentiate breast cancer patients from healthy controls. The Kyn/Trp ratio and Trp also showed different values according to hormone receptor status, TNM stage, T grade and histology. These results suggest a rapid metabolism in breast cancer, but no associations with outcome or sensitivity to chemotherapy were observed. [less ▲]

Detailed reference viewed: 43 (8 ULiège)
Peer Reviewed
See detailTowards an accurate cancer diagnosis modelization: Comparison of Random Forest strategies
Debit, Ahmed ULiege; Poulet, Christophe ULiege; JOSSE, Claire ULiege et al

Poster (2018, October 05)

Machine learning approaches are heavily used to produce models that will one day support clinical decisions. To be reliably used as a medical decision, such diagnosis and prognosis tools have to harbor a ... [more ▼]

Machine learning approaches are heavily used to produce models that will one day support clinical decisions. To be reliably used as a medical decision, such diagnosis and prognosis tools have to harbor a high-level of precision. Random Forests have been already used in cancer diagnosis, prognosis, and screening. Numerous Random Forests methods have been derived from the original random forest algorithm from Breiman et al. in 2001. Nevertheless, the precision of their generated models remains unknown when facing biological data. The precision of such models can be therefore too variable to produce models with the same accuracy of classification, making them useless in daily clinics. Here, we perform an empirical comparison of Random Forest based strategies, looking for their precision in model accuracy and overall computational time. An assessment of 15 methods is carried out for the classification of paired normal - tumor patients, from 3 TCGA RNA-Seq datasets: BRCA (Breast Invasive Carcinoma), LUSC (Lung Squamous Cell Carcinoma), and THCA (Thyroid Carcinoma). Results demonstrate noteworthy differences in the precisions of the model accuracy and the overall time processing, between the strategies for one dataset, as well as between datasets for one strategy. Therefore, we highly recommend to test each random forest strategy prior to modelization. This will certainly improve the precision in model accuracy while revealing the method of choice for the candidate data. [less ▲]

Detailed reference viewed: 48 (10 ULiège)
Full Text
See detailScreening of germline mutations in young Rwandan with breast cancer
Uyisenga, Jeanne ULiege; SEGERS, Karin ULiege; Lumaka Zola, Aimé ULiege et al

Scientific conference (2018, September 20)

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 ... [more ▼]

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 sys-tem for the screening of 26 genes associated with hereditary breast cancer from 40 pa-tients 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 includ-ing four patients (10%) carrying BRCA1 or BRCA2 pathogenic variants. One patient showed a missense likely pathogenic TP53 variant. We have also detected addi-tional 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 fac-tors in the development of breast cancer in young Rwandans [less ▲]

Detailed reference viewed: 40 (7 ULiège)
Full Text
Peer Reviewed
See detailPredictive and prognostic role of peripheral blood eosinophil count in triple-negative and hormone receptor-negative/HER2-positive breast cancer patients undergoing neoadjuvant treatment
ONESTI, Concetta Elisa ULiege; JOSSE, Claire ULiege; Poncin, Aurélie ULiege et al

in Oncotarget (2018)

In current clinical practices, up to 27% of all breast cancer patients receive neoadjuvant chemotherapy. High pathological complete response rate is frequently associated with tumor-infiltrating ... [more ▼]

In current clinical practices, up to 27% of all breast cancer patients receive neoadjuvant chemotherapy. High pathological complete response rate is frequently associated with tumor-infiltrating lymphocytes. Additionally, circulating immune cells are also often linked to chemotherapy response. We performed a retrospective analysis on a cohort of 112 breast cancer patients (79 triple-negative, 33 hormone receptor-negative/HER2-positive) treated with standard neoadjuvant chemotherapy. Eosinophil and lymphocyte counts were collected from whole blood at baseline and during follow-ups and their associations with pathological complete response, relapse, disease-free and breast cancer-specific survival were analyzed. We observed a higher pathological complete response rate in patients who presented at baseline a relative eosinophil count ≥ 1.5% (55.6%) than in those with a relative eosinophil count < 1.5% (36.2%)(p = 0.04). An improvement in breast cancerspecific survival in patients with high relative eosinophil count (p = 0.05; HR = 0.336; 95% CI = 0.107–1.058) or with high relative lymphocyte count (threshold = 17.5%, p = 0.01; HR = 0.217; 95% CI = 0.060–0.783) were also observed. Upon combining the two parameters into the eosinophil x lymphocyte product with a threshold at 35.8, associations with pathological complete response (p = 0.002), relapse (p = 0.028), disease-free survival (p = 0.012) and breast cancer-specific survival (p = 0.001) were also recorded. In conclusion, the relative eosinophil count and eosinophil x lymphocyte product could be promising, affordable and accessible new biomarkers that are predictive for neoadjuvant chemotherapy response and prognostic for longer survival in triplenegative and hormone receptors-negative/HER2-positive breast cancers. Confirmation of these results in a larger patient population is needed. [less ▲]

Detailed reference viewed: 70 (10 ULiège)
Full Text
See detailTowards an accurate cancer diagnosis modelization:Comparison of Random Forest strategies
Debit, Ahmed ULiege; JOSSE, Claire ULiege; JERUSALEM, Guy ULiege et al

Poster (2018, September 13)

Machine learning approaches are heavily used to produce models that will one day support clinical decisions. To be reliably used as a medical decision, such diagnosis and prognosis tools have to harbor a ... [more ▼]

Machine learning approaches are heavily used to produce models that will one day support clinical decisions. To be reliably used as a medical decision, such diagnosis and prognosis tools have to harbor a high-level of precision. Random Forests have been already used in cancer diagnosis, prognosis, and screening. Numerous Random Forests methods have been derived from the original random forest algorithm from Breiman et al. in 2001. Nevertheless, the precision of their generated models remains unknown when facing biological data. The precision of such models can be therefore too variable to produce models with the same accuracy of classification, making them useless in daily clinics. Here, we perform an empirical comparison of Random Forest based strategies, looking for their precision in model accuracy and over all computational time. An assessment of 15 methods is carried out for the classification of paired normal - tumor patients, from 3 TCGA RNA-Seq datasets: BRCA (Breast Invasive Carcinoma), LUSC (Lung Squamous Cell Carcinoma), and THCA (Thyroid Carcinoma).Results demonstrate noteworthy differences in the precision of the model accuracy and the overall time processing, between the strategies for one dataset, as well as between datasets for one strategy. Therefore, we highly recommend to test each random forest strategy prior to modelization. This will certainly improve the precision in model accuracy while revealing the method of choice for the candidate data. [less ▲]

Detailed reference viewed: 24 (1 ULiège)
Full Text
See detailRole of DNA methylation in INK4a-ARF-INK4b locus expression in breast cancer
Latgé, Guillaume ULiege; JOSSE, Claire ULiege; Poulet, Christophe ULiege et al

Poster (2018, September 13)

Breast cancer is a public health problem : one woman in 9 will suffer of it during her lifetime. The estrogen receptor expressing sub-type (ER+) is the most frequent, with 75 % of the cases. Those tumors ... [more ▼]

Breast cancer is a public health problem : one woman in 9 will suffer of it during her lifetime. The estrogen receptor expressing sub-type (ER+) is the most frequent, with 75 % of the cases. Those tumors frequently become resistant to hormonotherapy and spread as metastasis. In this case, chemotherapy needs to be administrated. The CDK4/6 inhibitors in combination with hormonotherapy appears as the new standard treatment for metastatic disease and allows to postpone the chemotherapy. Those drugs play the same role as the endogenous p16-p15 proteins, and it is expected that the patients who have lost their protein expression are also those who will present the best response to treatment. However, none of the currently tested biomarkers turns out to be predictive of treatment response. The INK locus, where p16/p14-p15 proteins are encoded, is often altered in cancers and is involved in cell cycle regulation. The p16/p14-p15 expression is negatively regulated by a non-coding RNA called ANRIL. My aim is to explore the molecular mechanisms linked to the non-coding RNA of the INK locus and involved in the expression regulation of the proteins p16/p14-p15, and to highlight potential biomarkers of the CDK4/6 inhibitors treatment response in ER+ breast cancer. To this end, I already collected In Vitro expression data by RT-qPCR in some cell lines with different expression patterns. DNA methylation are investigated thanks to a Deoxyazacytidine treatment, a DNA methylation inhibitor then by ImmunoPrecipitation of methylated DNA. So, the first links between the expression of the locus and its methylation can be done. In future, other treamtents, protein and RNA interactions will be studied to explain the potential links and molecular mechanisms. [less ▲]

Detailed reference viewed: 34 (2 ULiège)
Full Text
See detailPredictive and prognostic role of peripheral blood eosinophil count in triple negative and hormone receptor negative/HER2 positive breast cancers patients undergoing neoadjuvant treatment.
ONESTI, Concetta Elisa ULiege; JOSSE, Claire ULiege; PONCIN, Aurélie ULiege et al

Scientific conference (2018, September 13)

Introduction: In clinical practices, up to 27% of breast cancer (BC) patients receive neoadjuvant chemotherapy (NAC). In this context, a pathological complete response (pCR) is the most commonly used end ... [more ▼]

Introduction: In clinical practices, up to 27% of breast cancer (BC) patients receive neoadjuvant chemotherapy (NAC). In this context, a pathological complete response (pCR) is the most commonly used end-point. High pCR rate is frequently associated with tumor infiltrating lymphocytes. Besides, circulating immune cells are also often linked to chemotherapy response. Materials and methods: We performed a retrospective analysis on 112 BC patients (79 triple negative, 33 HR-/HER2+), treated with standard NAC. The median follow-up was 37.5 months (range 9-156). Eosinophil and lymphocyte count were collected at baseline, after surgery, at 1 year of follow-up and at relapse. The primary end-point is the association between the relative eosinophil count (REC) and pCR. The secondary end-points are the associations of REC, relative lymphocyte count (RLC) and eosinophil/lymphocyte product (ELP) with relapse, disease free (DFS) and breast cancer specific (BCSS) survival and to study the variation of REC and RLC during follow-up. Results: We observed a higher pCR rate in patients with REC≥1.5% vs patients with REC <1.5% (55.6% vs 36.2%, p = 0.04), and a higher median REC in patients with pCR (1.9% vs 1.2%, p 0.042). No statistically significant associations were detected with relapse, nor between RLC with pCR or relapse. We observed a 3-year BCSS of 91% vs 80% for high and low REC respectively (p 0.05; HR 0.336, 95% CI 0.107-1.058) and of 88% vs 49% in RLC≥17.5% and <17.5% respectively (p 0.01; HR 0.217, 95% CI 0.060-0.783). No significant differences were detected for DFS. Combining the two parameters in the ELP, we observed an association with pCR (59.6% in ELP≥35.8 vs 30.9% in ELP<35.8, p 0.002), relapse (12.3% vs 29.1% in high and low ELP, p 0.028), DFS (3-year DFS 90% vs 69% in high and low ELP, p 0.012; HR 0.337, 95% CI 0.138-0.823) and BCSS (3-year BCSS 95% vs 75% in high and low ELP, p 0.001; HR 0.129, 95% CI 0.029-0.573). Moreover, we observed a raise of REC after surgery from 1.4% to 2.6% (p 0.0001) and a significant reduction at relapse from 2.8% to 1.7% (p 0.021). Conversely, a reduction of RLC from 26.9% at baseline to 20.45% after surgery (p 0.0001), without significant variation at relapse, was detected. Conclusion: REC, RLC and ELP could be new promising, affordable and accessible biomarkers predictive for NAC response and prognostic for longer survival in TNBC and HR-/HER2+ BC. Confirmation in a larger cohort is needed. [less ▲]

Detailed reference viewed: 49 (7 ULiège)
Full Text
See detailGermline mutations in young Rwandan with breast cancers
Uyisenga, Jeanne ULiege; SEGERS, Karin ULiege; Lumaka Zola, Aimé ULiege et al

Poster (2018, September 11)

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 ... [more ▼]

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 sys-tem for the screening of 26 genes associated with hereditary breast cancer from 40 pa-tients 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 includ-ing four patients (10%) carrying BRCA1 or BRCA2 pathogenic variants. One patient showed a missense likely pathogenic TP53 variant. We have also detected addi-tional 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 fac-tors in the development of breast cancer in young Rwandans. [less ▲]

Detailed reference viewed: 26 (2 ULiège)