Practical notes on the current ESMO consensus guidelines for the management of patients with metastatic colorectal cancer in resource-constrained environments of low- to middle-income countries.

Letter (no abstract).

Novel BRCA2 pathogenic variant c.5219 T > G; p.(Leu1740Ter) in a consanguineous Senegalese family with hereditary breast cancer.

BACKGROUND: Pathogenic variants associated with hereditary breast cancer have been reported for BRCA1 and BRCA2 (BRCA1/2) genes in patients from multiple ethnicities, but limited information is available from sub-Saharan African populations. We report a BRCA2 pathogenic variant in a Senegalese family with hereditary breast cancer. METHODS: An index case from a consanguineous family and nineteen healthy female relatives were recruited after informed consent. Along with this family, 14 other index cases with family history of breast cancer were also recruited. For the control populations we recruited 48 healthy women with no cancer diagnosis and 48 women diagnosed with sporadic breast cancer without family history. Genomic DNA was extracted from peripheral blood. All BRCA2 exons were amplified by PCR and sequenced. Sequences were compared to the BRCA2 GenBank reference sequence (NM_000059.3) using Alamut Software. RESULTS: We identified a novel nonsense pathogenic variant c.5219 T > G; p.(Leu1740Ter) in exon 11 of BRCA2 in the index case. The pathogenic variant was also identified in three sisters and one daughter, but was absent in the controls and unrelated cases. CONCLUSIONS: This is the first report of a novel BRCA2 pathogenic variant in a Senegalese family with hereditary breast cancer. This result confirms the diversity of hereditary breast cancer pathogenic variants across populations and extends our knowledge of genetic susceptibility to breast cancer in Africa.

New Insights Into c.815_824dup Pathogenic Variant of BRCA1 in Inherited Breast Cancer: A Founder Mutation of West African Origin.

Founder mutations have been reported in BRCA1 and BCRA2 in different ethnic groups with inherited breast cancer. Testing of targeted mutations in specific populations is important for cancer prevention in mutation carriers. In Sub-Saharan Africa, only a few studies have reported specific founder mutations in inherited breast cancer. The pathogenic variant c.815_824dup of BRCA1 has been reported as the most frequent among African American populations with inherited breast cancer and was supposed to have a West African origin. Recent report from Senegal identified this variant in women with inherited breast cancer at the highest frequency ever reported. The variant was linked to a common haplotype confirming its founder effect in West Africa. In this article, we review the mutation history of c.815_824dup and discuss how it spread out of Africa through the transatlantic slave trade.

Evidence for an ancient BRCA1 pathogenic variant in inherited breast cancer patients from Senegal.

BRCA1 and BRCA2 are the most incriminated genes in inherited breast/ovarian cancers. Several pathogenic variants of these genes conferring genetic predisposition have been described in different populations but rarely in sub-Saharan Africa. The objectives of this study were to identify pathogenic variants of the BRCA genes involved in hereditary breast cancer in Senegal and to search for a founder effect. We recruited after free informed consent, 27 unrelated index cases diagnosed with breast cancer and each having a family history. Mutation screening of the genes identified a duplication of ten nucleotides c.815_824dupAGCCATGTGG, (p.Thr276Alafs) (NM_007294.3) located in exon 11 of BRCA1 gene, in 15 index cases (allelic frequency 27.7%). The pathogenic variant has been previously reported in African Americans as a founder mutation of West African origin. Haplotypes analysis of seven microsatellites surrounding the BRCA1 gene highlights a shared haplotype encompassing ~400 kb between D17S855 and D17S1325. This haplotype was not detected in none of 15 healthy controls. Estimation of the age of the pathogenic variant suggested that it occurred ~1400 years ago. Our study identified a founder pathogenic variant of BRCA1 predisposing to breast cancer and enabled the establishment of an affordable genetic test as a mean of prevention for Senegalese women at risk.

Quality of Life During Chemotherapy for Breast Cancer in a West African Population in Dakar, Senegal: A Prospective Study.

PURPOSE: The prevalence of breast cancer is increasing in low- to middle-income countries such as Senegal. Our prospective study assessed the quality of life (QoL) of patients with breast cancer undergoing chemotherapy in Senegal. PATIENTS AND METHODS: Our study included women with breast cancer undergoing chemotherapy as initial treatment at the Center Aristide Le Dantec University Hospital in Dakar. Clinical, sociodemographic, and QoL data were collected and analyzed at three different times: baseline, 3 months, and 6 months after the start of systemic therapy. Health-related QoL was assessed using a Functional Assessment of Cancer Therapies-Breast (FACT-B) questionnaire after translation into the Wolof language. Linear mixed-effects models were performed to assess the changes in QoL scores. RESULTS: Between July 2017 and February 2018, 120 patients were included in the study. Their median age was 45 years. Most patients (n = 105; 92%) had locally advanced disease (T3 to T4 stage) and lymph node involvement (n = 103; 88%), and half had metastatic disease. The FACT-B total scores significantly improved over time (ß = 1.58; 95% CI, 0.50 to 2.67; P < .01). Nausea and vomiting were significantly associated with a decrease in FACT-B total scores (ß = -16.89, 95% CI, -29.58 to -4.24, P = .012; and ß = -13.44, 95% CI, -25.15 to -1.72, P = .028, respectively). CONCLUSION: Our study confirmed the feasibility of standardized QoL assessment in Senegalese patients with breast cancer. Our results indicated a potential improvement of QoL over the course of chemotherapy. Optimizing nausea and vomiting prevention may improve QoL.

Malignant chondroid syringoma in a West African cancer institute: A case report.

OBJECTIVE: To report a case of malignant chondroid syringoma, a rare skin tumor at Joliot Curie Cancer Institute in Dakar. RESULTS: We report a case of malignant chondroid syringoma of the deltoid and axilla in a 53year old patient. Malignant chondroid syringoma is an extremely rare tumor of the sweat glands. It is included in myoepithelial tumors of the skin. It has an epithelial component with eccrin or apocrin differentiation, and myoepithelial component. It preferentially seat at the extremities. We report an unusual case with deltoid presentation and axillary mass masqueriding as metastatic lymph node. Surgery is the main treatment. It has a poor prognosis.

Embryonal rhabdomyosarcoma of the perineum in an adult: a case report.

BACKGROUND: We report the case of an adult patient with embryonal rhabdomyosarcoma of the perineum admitted to our practice at Joliot Curie Institute in Dakar. It is a rare tumor at this age and has a bad prognosis at this localization. CASE PRESENTATION: We describe the case of a 22-year-old African man admitted for a perineal mass that had evolved over 6 months. He complained of tenesmus, obstinate constipation, and dysuria. A clinical examination revealed perineal swelling spread over his anus, scrotum, penis, testicles, and inguinal lymph nodes. A perineal ultrasound and computed tomography scan showed a large mass driving his testicles forward with regional lymph node metastases. An ultrasound-guided biopsy showed embryonal rhabdomyosarcoma on histology and immunohistochemistry, with strong positivity of neural cell adhesion molecule and myogenin while results for cytokeratin AE1/AE3, cluster of differentiation 45, synaptophysin, and chromogranin were negative. Our patient was classified T2N1M1. Outcome was quickly marked by occlusive syndrome and colostomy. Our patient did not opt for chemotherapy and died after 6 months of follow-up. CONCLUSIONS: The embryonic RMS of the adult is a rare disease. Despite the sensitivity to chemotherapy and surgery. Localization to perineum remains poor prognosis.

[Synchronous bilateral breast cancer and pregnancy: about 3 cases at Joliot Curie institute of Dakar (Senegal)]. / Cancers du sein bilatéraux synchrones et grossesse a l'institut Joliot Curie de Dakar (Sénégal).

To describe our diagnostic and therapeutic strategy against synchronous, bilateral breast cancer during the pregnancy. Gestational age at diagnosis of cancer was 7; 21 and 25 weeks respectively. Patients had stage IV and IIIA of breast cancer in two and one case respectively. They all received chemotherapy, two cases during pregnancy (6TEC and 3AC) and one case after delivery. Bilateral mastectomy was performed in one case. One patient died. The others were alive but all metastatic. Fetal growth restriction was noted in one case. This association leads to delayed diagnosis of cancer. Surgery is feasible and the type of intervention is only determined by the cancer stage. Chemotherapy is feasible and is associated with less foetal complications in the last two quarters of pregnancy.

[Arrival of patients at advanced stage: tempting to identify responsibility]. / Arrivée des malades cancéreux aux stades avancés: tentative d'identification de responsabilité

JUSTIFICATION: In many publications on cancer in Africa, the majority of patients were seen in advanced stages (III or IV) during the first consultation. So, it was important to look for factors that explain this situation. METHODS: A survey by questionnaire was made in our Medical Oncology Department of University Teaching Hospital of Brazzaville from January to October 2010. The responsibility of advice to go to hospital was codified in Arrival in Advanced Stage (AAS) from the weakest (AAS 1) to the strongest (AAS 8) according to the knowledge in oncology. The impact of organ accessibility and the patient's instruction level were also evaluated. RESULTS: One hundred and ninety-six patients seen in consultation, hospital day and hospitalization were asked and we had gathered the same information in patients' medical files. Our sample was essentially made by women (67,4%). The age of patients were from 21 to 83 years old with average of 53,8. The direct responsibility of the patient was weak (24,4%) by ignorance or fear of diagnosis. The hospital personal, the nurses and physicians who work in private were for a great part: 40,8%. The number of practitioners by category had limited the results because of the difficulty to join them. The medical doctor, specialist or not, were responsible at 25,5%. CONCLUSION: The medical vulgarization, large information, specialization training adapted were the way to choose in the resolution of the problem, which impact on therapeutic result was undeniable.

[Diagnosis and treatment of the epithelial ovarian cancer at the West African Cancer Center of Dakar]. / Prise en charge diagnostique et thérapeutique des tumeurs épithéliales malignes de l'ovaire dans le Centre Ouest-Africain de lutte Contre le Cancer de Dakar.

INTRODUCTION: Epithelial ovarian cancer are the most frequent of ovarian cancer, their prognosis is very bad. The aim of this study is to describe the diagnosis, the treatment and to assess the survival rate of the patients. METHODS: It was a retrospective study realized at the Cancer Institute of Dakar from December 2000 to January 2007. We have collected 117 patients with epithelial ovarian cancer. The mean age was 49 years. Patients were comprised: 22 stage I, 32 stage II, 35 stage III and 26 stage IV. Primary surgery was performed to 34 patients and the other patients were treated with chemotherapy and surgery. The survival rate was assessed by Kaplan-Meier method and the Logrank test had allowed to compare the survival among age and optimal surgery. RESULTS: Optimal surgery R0 was done in 20 cases and surgical resection R2 was performed in 45 cases. Pathological exam had found 65 serous cystadenocarcinoma, 28 mucinous cystadenocarcinoma and 21 endometrioid cystadenocarcinoma, one malignant tumor of Brenner. Overall survival at five years was 13.3%. The survival among optimal surgery was 16.3 and 2.3% for suboptimal surgery. There was no significant difference of the survival among patients who were less than 40 years old (P = 0.334). CONCLUSION: Prognosis of epithelial ovarian cancer is worse in Senegal as like as in the world. To improve the survival of our patients, we must detect the early diagnosis of these tumors and to introduce the neoadjuvant chemotherapy before optimal surgery.