RESUMO
Women with triple negative breast cancer (TNBC) have a high prevalence of BRCA1 mutations, and current clinical guidelines recommend genetic testing for patients with TNBC aged ≤60â¯years. However, studies supporting this recommendation have included few older women with TNBC. METHODS: Genetic testing results from women aged >60â¯years with TNBC enrolled in the Clinical Cancer Genomics Community Research Network (CCGCRN) registry were included in this analysis. Prevalence of breast cancer-associated pathogenic variants (PVs) was compared across age groups. RESULTS: We identified 151 women with TNBC aged >60â¯years (median 65â¯years; SD 5.3). Of these, 130 (86%) underwent genetic testing, and a breast cancer-associated PV was identified in 16 (12.3%; 95% CI 7-19): BRCA1 (nâ¯=â¯6), BRCA2 (nâ¯=â¯5), PALB2 (nâ¯=â¯2), ATM (nâ¯=â¯1) and RAD51C (nâ¯=â¯2). We found no differences in the proportion of patients with close blood relatives with breast (≤50â¯years) or ovarian cancer (any age) between PV carriers (37.5%) and non-carriers (34.2%) (pâ¯=â¯0.79). Among PV's carriers, the proportion of older women with a BRCA1 PV was lower when compared to younger women (37.5% vs 77.2%; pâ¯<â¯0.01). CONCLUSION: Breast cancer-associated PVs were found in an important proportion of women aged >60â¯years with TNBC undergoing genetic testing, including greater representation of BRCA2. These results suggest that older women with TNBC should be offered genetic testing, and that their exclusion based on chronologic age alone may not be appropriate.
Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Neoplasias de Mama Triplo Negativas , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Feminino , Testes Genéticos , Humanos , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genéticaRESUMO
BACKGROUND: Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America. METHODS: Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome. RESULTS: We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet. CONCLUSION: The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.