Clinicopathological and Molecular Study of Triple-Negative Breast Cancer in Algerian Patients

Gaceb, Hadjer; Cherbal, Farid; Bakour, Rabah; Ould-Rouis, Abdelhalim; Mahfouf, Hassen

doi:10.1007/s12253-017-0242-2

Cited by 10 publications

(9 citation statements)

References 49 publications

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“…Thus, the clinical data associated to exon 11 mutations tend to be homogeneous. As for the pathological data, most of BRCA1 mutations located in exon 11 have been correlated with high grade TNBC, large tumor size (>2cm) and poor prognosis, as our patient, leading to a genotype phenotype correlation [22][23][24][25][26][27][28].…”

Section: Discussionmentioning

confidence: 59%

“…As well, in this Tunisian family, detection of this mutation in relative's diagnostic with BC or ovarian cancer would have been an additional argument in favour of the segregation of this mutation with the disease. Several studies reported different disease phenotypes among patients carrying mutations in exon 11 of BRCA1 compared to other BRCA1 germline mutations [22][23][24][25][26][27][28]. Rebbeck et al (2015) reported a total of 19 581 females carrying BRCA1 mutation of which 1132 had a nonsense mutation in exon 11, 796 BC and 336 ovarian cancer, with a mean age at cancer diagnosis 40, 4 and 50, 2-year-old respectively, likewise our IC who had an early onset age of cancer (BC: 38 years old, ovarian cancer: 50-years-old) [29].…”

Section: Discussionmentioning

confidence: 99%

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Identification of Novel BRCA1 Germline Deleterious Variant Among a Tunisian Family

Sahli¹,

Meddeb²,

Trabelsi³

et al. 2021

COR

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Inherited predisposition to breast and ovarian cancer are most frequently due to germline mutations in the main genes BRCA1 (OMIM# 113705) and BRCA2 (OMIM# 600185). These inactivating mutations, essentially frameshift and nonsense variation, occurs mainly across conserved regions. The aim of the present study is to report a novel germline BRCA1 mutation identified in a Tunisian family case with early onset of breast and ovarian cancer and to evaluate the genotype phenotype correlation. The proband had high-grade tumors, invasive unilateral ductal carcinoma developed at the age of 38 and a serous ovarian adenocarcinoma after a gap of twelve years. The molecular analysis revealed a novel heterozygous nonsense BRCA1 mutation NM_007294.4: c.915T>A p.(C305*) in the proband and her daughter. This mutation leads to a truncated protein which pathogenicity was validated by bioinformatics tools. This variant is subject to nonsense-mediated mRNA decay. We also underlined the immunohistochemistry usefulness by lack of expression of BRCA1 protein in paraffin embedded breast tumor contrasting with normal tissue. Clinical and pathological data tend to be homogeneous and led to the conclusion that there is a genotype phenotype correlation in BRCA1, an element that must be taken into account in genetic counselling. Conclusively, we are the first to report this novel BRCA1 germline likely deleterious variant extending the molecular and clinical spectrum of BRCA1 pathogenic point mutations. Further in vitro functional experiments needs to be established. High-risk individuals carrying this BRCA1 mutation benefit from preventive measures to reduce morbidity.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Identification of Novel BRCA1 Germline Deleterious Variant Among a Tunisian Family

Sahli¹,

Meddeb²,

Trabelsi³

et al. 2021

COR

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“…It has been also found in the United Kingdom [1]. More recently, it has been reported in Algeria in three young patients aged 33, 34 and 38 years respectively, all with triple negative cancer and a family history of breast and/or prostate cancer [47].…”

Section: Discussionmentioning

confidence: 79%

“…It was also identified in two Tunisian and Algerian families with a common haplotype to all carriers of this mutation [20], suggesting the presence of the first non-Jewish founder effect in North Africa. It was later identified in four Algerian patients [21,47], three Moroccan women [16,17] and five Tunisian women [22], all with a family history of breast or ovarian cancer and aged between 34 and 44 years.…”

Section: Discussionmentioning

confidence: 99%

Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco

et al. 2020

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Background To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco. Methods Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform. Results Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A > G). Most BRCA mutations carriers (80%) had no family history of breast cancer. Conclusion Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (≤40 years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.

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“…2 This finding is in agreement with previous studies in patients with TNBC from Tunisia. 15 A recent study conducted in Morocco highlighted the high frequency of BC in young women as compared with Western countries. 23 In this study, both TNBC and non-TNBC cases prevail in younger women, with no statistical difference between the 2 groups.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological, Treatment and Event-Free Survival Characteristics in a Moroccan Population of Triple-Negative Breast Cancer

Mouh

Slaoui

Rachid

et al. 2020

Breast Cancer�(Auckl)

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Introduction: Triple-negative breast cancer (TNBC) is a group of breast carcinoma characterized by the lack of expression of estrogen and progesterone hormone receptors (ER, PgR) and HER2. This form is also characterized by its aggressiveness, a low survival rate, and the absence of targeted therapies. This study was planned to evaluate the clinical features, treatment, and prognosis characteristics of TNBC in a population of Moroccan patients. Methods: In this retrospective study, a total of 905 patients diagnosed with breast cancer at the National Institute of Oncology in Rabat, Morocco, have been included. Based on molecular subtype, patients were divided into 2 categories: TNBC and non-TNBC patients. Data were recorded from patients’ medical files and analyzed using SPSS 13.0 software (IBM). Results: Overall, 17% of the patients had TNBC. At diagnosis, the median age of TNBC cases was 47 years, with extreme ages of 40 and 55 years. The median follow-up time was 30 months (10-53 months) and the 3-year survival rate was 76%. No significant difference was observed among the patients in terms of age at diagnosis, age at menarche, age at the time of first birth, nulliparity, oral contraception, and family history of breast cancer. Menopausal status and the number of pregnancy were significantly higher in the non-TNBC group. The percentage of grade 3 (G3) tumors was higher in the TNBC group ( P < .001). Using neoadjuvant, adjuvant chemotherapy and radiotherapy, a net benefit in the event-free survival was registered for the 2 groups. Conclusions: This retrospective study was very informative and showed that women with TNBC had a less favorable prognosis than non-TNBC cases. Clinical data demonstrated that risk factors including age, premenopausal status, parity, hormonal contraceptive use, advanced disease, and a high histologic grade were independently associated with TNBC. However, large tumors and high Scarff-Bloom and Richardson grade prevail in TNBC cases with a higher incidence of lymph node metastases.

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Clinicopathological and Molecular Study of Triple-Negative Breast Cancer in Algerian Patients

Cited by 10 publications

References 49 publications

Identification of Novel BRCA1 Germline Deleterious Variant Among a Tunisian Family

Identification of Novel BRCA1 Germline Deleterious Variant Among a Tunisian Family

Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco

Clinicopathological, Treatment and Event-Free Survival Characteristics in a Moroccan Population of Triple-Negative Breast Cancer

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