Patient clinical features of BC and OC and cancer family history were collected and compared to the patient genetic profile.A total of 255 women were analyzed, 57 of whom had a pathogenic mutation in BRCA1/2 genes, and 17 carried pathogenic mutations in other genes, such as PALB2, ATM, BRIP1, RAD51D, MSH6, PPM1D, RECQL4, ERCC3, TSC2, SLX4 and other Fanconi anemia genes.Patients with a pathogenic mutation in genes other than BRCA1 and BRCA2 showed no significant difference from the BRCA1/2-mutated carriers with respect to age at diagnosis and clinical features, suggesting that mutations in other genes could pose a high risk of cancer development.These patients had a much higher percentage of bilateral breast cancer (BBC) and a lower rate of OC than BRCA-mutated patients and patients with no pathogenic mutations: as a consequence, the surveillance protocol should be customized to the patient genetic characteristics.
Genetic testing of the family members indicated that the same double heterozygosity for BRCA1 and BRCA2 genes was transmitted to the paternal cousin, and the same BRCA2 mutation to the younger sister with bilateral breast cancer, younger brother with stomach cancer, and proband's son and daughter without cancer.
We studied 1,504 women with a known BRCA1 or BRCA2 mutation, 411 women with bilateral breast cancer (cases) and 1,093 women with unilateral breast cancer (controls) in a matched case-control study.
This report discusses the appropriate genetics evaluation for a patient with bilateral breast cancer at a young age, including testing for mutations in BRCA1 and BRCA2, followed, if negative, by consideration of testing for mutations in TP53 (Li-Fraumeni syndrome).
In the course of mutation screening of the BRCA1 and BRCA2 genes in a hospital based series of patients with risk factors for hereditary breast/ovarian cancer, we identified a novel germ line mutation in the BRCA2 gene (c.51dupA) in a patient with early onset bilateral breast cancer and no family history of the disease.
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.
This study assessed the pathological mutation detection rates for BRCA1, BRCA2 and the CHEK2c.1100 delC mutation in 2022 women with breast cancer, including 100 with breast/ovary double primary and 255 with bilateral breast cancer.
Exclusion criteria were an estimated lifetime risk < 20%, BRCA1/BRCA2 mutation, noninvasive carcinoma (ductal or lobular carcinoma in situ), and bilateral breast carcinoma.
Three BRCA2 mutations were found in patients with breast cancer without family history: two in young patients and one in patients with bilateral breast cancer.
In summary, we did not find a significantly increased prevalence of BRCA1 and BRCA2 mutations in a hospital-based cohort of German patients with bilateral breast cancer.
To appreciate the contribution of genetic determinants to bilateral breast cancer in Jewish women we genotyped 55 such women for the three predominant mutations in BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) that account for the overwhelming majority of BRCA mutations in high-risk Jewish families.
TP53 mutation carriers were significantly more likely to have early onset cancer (p < 0.001) and bilateral breast cancer (p = 0.03), they and were significantly more likely to respond to carboplatin-based neoadjuvant chemotherapy compared to anthracycline- or taxane-based regimen in terms of pathologic complete response (50% vs. 0%, p = 0.006).
While characterizing an LFS family with a documented defect in TP53, we found one family member who developed bilateral breast cancer at age 37 yet was homozygous for wild-type TP53.
No convincing evidence was found for other associations between the paired tumours or for a high prevalence of p53 alterations in bilateral breast cancer.
No concordant allelic loss was demonstrated for D17S786 suggesting that germline mutations in p53 are unlikely in such cases of bilateral breast cancer.
Thus, the present study focused on investigating the incidence of p53 gene abnormality in bilateral breast cancer and its correlation with proliferative activity and nuclear cytomorphology to demonstrate its significance in biological behavior and predicting the relatively small percentage of second tumors in the contralateral breast.
Immunohistochemical analysis of p53 protein with a monoclonal antihuman p53 antibody showed concordant positivity between the right and left tumors in three bilateral breast cancer cases.