Mutational analysis ofBRCA1andBRCA2in Mediterranean Spanish women with early-onset breast cancer: Identification of three novel pathogenic mutations

Aim of the study. Aim of the study was to estimate the occurrence of pathogenic mutations in the BRCA1 gene in Russian breast cancer patients.Material and methods. Complete coding sequence of the BRCA1 gene of 445 early onset breast cancer patients (under 40 years) from Novosibirsk region (Russia) were analyzed by targeted Next Generation Sequencing (NGS) using Ion Torrent platform. Results. Forty (9%) carriers of various pathogenic mutations were revealed. Thirty five (7,9%) patients carried 5382insC mutation, described earlier as a founder mutation for Slavic population. Five (1.1%) patients carried various pathogenic mutations, namely C61G, 462delCC, E143X, 4153delA, and IVS18+1G>T. Besides, 29 genetic variants with no clinical significance or with unknown clinical significance were detected in BRCA1 gene among 445 early onset breast cancer patients. Conclusions. Data on the frequency of genetic variations in the BRCA1 gene among early onset breast cancer patients in the Novosibirsk Region (Russia) were obtained. Proportion of the 5382insC mutation is 87.5% of all pathogenic mutations in the BRCA1 gene found in patients.

Download Full-text

Oral Contraceptive Use and Risk of Early-Onset Breast Cancer in Carriers and Noncarriers of BRCA1 and BRCA2 Mutations

Yearbook of Obstetrics Gynecology and Women s Health ◽

10.1016/s1090-798x(08)70471-5 ◽

2006 ◽

Vol 2006 ◽

pp. 269-270

Author(s):

L.P. Shulman

Keyword(s):

Breast Cancer ◽

Oral Contraceptive ◽

Early Onset ◽

Contraceptive Use ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Oral Contraceptive Use ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

Download Full-text

High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer

Journal of Medical Genetics ◽

10.1136/jmedgenet-2020-107347 ◽

2021 ◽

pp. jmedgenet-2020-107347

Author(s):

D Gareth Evans ◽

Elke Maria van Veen ◽

Helen J Byers ◽

Sarah J Evans ◽

George J Burghel ◽

...

Keyword(s):

Breast Cancer ◽

Early Onset ◽

Ductal Carcinoma ◽

Cancer Genes ◽

Early Onset Breast Cancer ◽

Younger Women ◽

Pathogenic Variants ◽

Younger Age ◽

Predisposition Genes

BackgroundWhile the likelihood of identifying constitutional breast cancer-associated BRCA1, BRCA2 and TP53 pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease.MethodsSequencing of BRCA1, BRCA2, TP53 and CHEK2 c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study.ResultsTesting 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in BRCA1, 35 (9.2%) in BRCA2, 22 (5.8%) in TP53 and 2 (0.5%) CHEK2 c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. BRCA1/2 PVs were more common in women aged 26–30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma in situ (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (TP53=6, BRCA2=2, BRCA1=2, PALB2=1). This PV yield is similar to the 61 (48.8%) BRCA1/2 PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower TP53 PV rates in this group (1.7%).ConclusionThe rates of BRCA1, BRCA2 and TP53 PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes.

Download Full-text