Multigene panel testing results in patients with multiple breast cancer primaries

Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants in Other Genes beyond BRCA1/2

“…In recent years, the increasing BC incidence rates observed through screening programs, improved treatment, and growing life expectancy have resulted in the early detection of increasing incidence of developing BBC [1,4]. Multiple criteria are associated with increased risk of second primary BC, including an early age of onset, hormone receptor-positivity of the initial tumor, race and ethnicity, as well as presence of known pathogenic variants (PVs) in hereditary cancer-associated genes [5]. Although BC is frequently a sporadic tumor (75-80%), approximately 15-20% are familial type and about 5-10% of cases are hereditary, caused by germline PVs in specific breast cancer-associated genes [5][6][7][8].…”

“…Multiple criteria are associated with increased risk of second primary BC, including an early age of onset, hormone receptor-positivity of the initial tumor, race and ethnicity, as well as presence of known pathogenic variants (PVs) in hereditary cancer-associated genes [5]. Although BC is frequently a sporadic tumor (75-80%), approximately 15-20% are familial type and about 5-10% of cases are hereditary, caused by germline PVs in specific breast cancer-associated genes [5][6][7][8]. The two genes mainly involved in the BC genetic predisposition are BRCA1, located on chromosome 17 [9] and BRCA2, located on chromosome 13 [10].…”

“…Additionally, the Italian guidelines, established by the Italian Medical Oncology Association (AIOM), provide the same recommendation, also suggesting to perform the genetic tests on patients with a personal history of BC diagnosed before age 50 years with a family history of one or more first-degree relatives with BBC. With the increase in the acquisition of multi-gene panels, genetic testing used for detecting alterations in other genes beyond BRCA1 and BRCA2 has become more prevalent [5,7]. Moreover, the role of genetic testing in BC is rapidly changing, becoming an interesting area of research.…”

Literature Review of BARD1 as a Cancer Predisposing Gene with a Focus on Breast and Ovarian Cancers

“…These findings are interesting because these variants may result in partial or complete loss of BARD1 protein. In studies of ≥500 cancer cases, the prevalence of potentially pathogenic BARD1 variants ranged from 0.18-0.53% [11,47], 0.67-0.9% [13,22], and 0.07-0.23% [37,63] in BC, TNBC and OC cases, respectively. Clearly, in BC and OC cases carriers of BARD1 variants are much less common than carriers of pathogenic BRCA1/BRCA2 variants (5-10% each).…”

“…There are barriers to estimating risk for BARD1 variants: i) the rarity of carriers of potentially pathogenic BARD1 variants; ii) the posited low-moderate risk of cancer associated with BARD1 variants; and iii) the heterogeneity within and between populations, cancer cases of the same primary tissue site and cancer subtypes (based on histopathology or biomarkers). A family-based study estimated that the relative risk associated with BARD1 carriers was 2.27 (95%CI 0.47-18.91) for BC [47], suggesting that women with a family history of BC have at least a two-fold increased risk for this disease as compared with those who do not. However, the wide confidence interval, reflecting small sample groups in this study, suggest that this information should be viewed with caution.…”