First description of a double heterozygosity for BRCA1 and BRCA2 pathogenic variants in a French metastatic breast cancer patient: A case report

Meynard, Guillaume; Mansi, Laura; Lebahar, P; Villanueva, Cristian; Klajer, Elodie; Calcagno, Fabien; Vivalta, Adrian; Chaix, Marie; Collonge‐Rame, Marie‐Agnès; Populaire, Céline; Algros, Marie‐Paule; Colpart, Prudence; Neidich, Julie; Pivot, Xavier; Curtit, Elsa

doi:10.3892/or.2017.5422

Cited by 9 publications

(11 citation statements)

References 14 publications

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“…In two papers we have amended the calculation of two patients ( Table 1 ) [ 17 , 18 , 19 ]. From 1998 to 2017, 19 articles described 33 families with 54 subjects carrying a double BRCA mutation [ 2 , 8 , 9 , 17 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. Table 1 summarizes the main data, including ethnicity, description of mutations, matrilineal or patrilineal transmission of variants, cancer type and age of onset, for a total of 56 cases (34 probands and 22 relatives), with the addition of our current report.…”

Section: Resultsmentioning

confidence: 99%

“…In this population, three founder mutations, BRCA1 185delAG, BRCA1 5382insC and BRCA2 6174delT, are particularly common with an approximate frequency of 1%, 0.1%, and 1.4%, respectively [ 6 , 7 , 43 ]. Therefore, on the basis of predictive statistical calculations, the population carrier frequency of BRCA1 and BRCA2 mutations in the Ashkenazi population should be approximately 3%, with a presumable occurrence of double heterozygosity of 1 in 1800 individuals [ 8 , 9 ]. In a BRCA1 and BRCA2 mutational study performed on 10,000 subjects, including 3022 Ashkenazi, Frank et al, identified double mutations exclusively in the Ashkenazi population with a frequency of 11 of the 3022 tested individuals (0.36%), and 11 on 617 positive cases (1.8%) [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…For the same reasons, the presence of double mutations of BRCA1 and BRCA2 is extremely rare in the general population, although not exceptional in Ashkenazi breast-cancer patients [ 4 ]. Compared to the huge amount of mutational analysis data for BRCA1 and BRCA2 genes, only a few studies report dual mutations in non-Ashkenazi subjects, mostly consisting in the description of a single or of a small number of families [ 4 , 5 , 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Double Heterozygosity for BRCA1 Pathogenic Variant and BRCA2 Polymorphic Stop Codon K3326X: A Case Report in a Southern Italian Family

Palmirotta

Lovero

Stucci

et al. 2018

IJMS

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Here, we describe a patient with bilateral breast cancer and melanoma, and with a concomitant double variant, namely p.Gln563Ter in BRCA1 and p.Lys3326Ter in BRCA2. The BRCA2 p.Lys3326Ter (K3326X) (rs11571833) mutation identified in our patient is a debated substitution of thymidine for adenine which is currently regarded as benign polymorphism in main gene databases. Recent studies, however, describe this variant as associated with breast and ovarian tumors. Based on the observation of the cancer’s earliest age of onset in this subject, our purpose was to reevaluate this variant according to recent papers indicating a role of powerful modifier of the genetic penetrance. Genetic testing was performed in all consenting patient’s relatives, and in the collection of the clinical data particular attention was paid to the age of onset of the neoplasia. Following our observation that the our patient with double heterozygosis had an early age of onset for cancer similar to a few rare cases of double mutation for BRCA1 and BRCA2, we also performed an extensive review of the literature relative to patients carrying a double heterozygosity for both genes. In line with previous studies relative to the rare double heterozygosity in both BRCA1/2 genes, we found the earlier onset of breast cancer in our patient with both BRCA1/2 mutations with respect to other relatives carrying the single BRCA1 mutation. The presence of the second K3326X variant in our case induces a phenotype characterized by early onset of the neoplasia in a manner similar to the other cases of double heterozygosity previously described. Therefore, we suggest that during the genetic counseling, it should be recommendable to evaluate the presence of the K3326X variant in association with other pathogenic mutations.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Double Heterozygosity for BRCA1 Pathogenic Variant and BRCA2 Polymorphic Stop Codon K3326X: A Case Report in a Southern Italian Family

Palmirotta

Lovero

Stucci

et al. 2018

IJMS

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“…Other risk factors appear to be specific to non-menopausal female patients (13). Furthermore, a study published in 2006 suggested that the recent use of oral contraceptives, particularly in young nulligravidae was associated with an increased risk of breast cancer prior menopause (14). While obesity is a recognized risk factor in post-menopausal patients, it can function as a protective factor in young female patients (13,14).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a study published in 2006 suggested that the recent use of oral contraceptives, particularly in young nulligravidae was associated with an increased risk of breast cancer prior menopause (14). While obesity is a recognized risk factor in post-menopausal patients, it can function as a protective factor in young female patients (13,14). The risk of breast cancer is also higher in young female patients of African descent, compared with in Caucasian female patients, as has been demonstrated in the USA (15).…”

Section: Discussionmentioning

confidence: 99%

Breast cancer cases of female patients under 35ï¿½years of age in Togo: A series of 158ï¿½cases

et al. 2017

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Abstract. Breast cancer in young female patients represents a public health problem in developing countries. The objectives of the study were to study the epidemiological and histological characteristics of breast cancer in female patients under 35 years of age. This was a retrospective analytical study of a series of 158 cases of breast cancer in female patients under 35 years of age, conducted at the University Teaching Hospital of Lomé between 2000 and 2015. A total of 158 cases were collected, representing 36.2% (436) of all breast cancer cases. The average age of the patients was 30.9 years (range, 16-35 years). A family history of breast cancer at the 1st or 2nd degree was identified in 13.9% of cases. Genetic mutation studies were carried out for 7 patients, 5 of which revealed mutations (4 BRCA1 and 1 BRCA2). According to the locus, the cancer was located preferentially in the left breast in 88 cases (55.7%). Malignant mammary lesions were epithelial tumors (n=144 cases, 91.1%), infiltrating (n=125 cases, 79.1%) and non-infiltrating (n=19 cases, 12.0%). The other histological groups consisted of 8 cases of sarcomas (5 cases of angiosarcoma, 2 cases of fibrosarcoma and 1 case of Kaposi's sarcoma), 5 cases of lymphomas and one case of melanoma. Not otherwise specified infiltrating ductal carcinomas were SBR II and III in 43.2 and 35.2% of cases, respectively. The tumors classified as T4 were the most frequent (30.4%). Regarding the lymph node status, lymph node metastasis was noted in 22.8% of cases. Studies of hormone receptors were carried out in 23 patients and were positive for 11 patients: Estrogen receptor (ER)+plus progesterone receptor (PR)+(7 patients), ER+PR-(4 patients). Of the aforementioned 8 cases of sarcoma, 5 were angiosarcoma. The lymphomas were predominantly Burkitt's type for 4 cases. Mammary ultrasonography was performed in 45.6% of the patients and 54.4% underwent the combined ultrasonography and mammography. Ultrasound identified one or more sign of malignancy in 67 patients (42.4%), and combined ultrasonography and mammography classified 51.9% of lesions in BIRADS 4 and 5. The incidence of breast cancer in young Togolese patients is high. It is a disease distinguished by a delay in diagnosis, which contributes to the high number of cases that initially diagnosed at an advanced stage, particularly the high histo-prognosis grades of infiltrating ductal carcinoma. These results indicate a genetic origin; therefore, a thorough investigation into genetic mutations should be carried. In addition, further collaborative studies are required to verify these results.

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Concurrent pathogenic variations in patients with hereditary cancer syndromes

Ağaoğlu

Doganay

2021

European Journal of Medical Genetics

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First description of a double heterozygosity for BRCA1 and BRCA2 pathogenic variants in a French metastatic breast cancer patient: A case report

Cited by 9 publications

References 14 publications

Double Heterozygosity for BRCA1 Pathogenic Variant and BRCA2 Polymorphic Stop Codon K3326X: A Case Report in a Southern Italian Family

Double Heterozygosity for BRCA1 Pathogenic Variant and BRCA2 Polymorphic Stop Codon K3326X: A Case Report in a Southern Italian Family

Breast cancer cases of female patients under 35ï¿½years of age in Togo: A series of 158ï¿½cases

Concurrent pathogenic variations in patients with hereditary cancer syndromes

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