Eleni Zografos1, Anna-Maria Korakiti1, Angeliki Andrikopoulou1, Ioannis Rellias2, Constantine Dimitrakakis2, Spyridon Marinopoulos2, Aris Giannos2, Antonios Keramopoulos3, Nikolaos Bredakis3, Meletios-Athanasios Dimopoulos1, Flora Zagouri4. 1. Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528, Athens, Greece. 2. Department of Obstetrics and Gynecology, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. 3. Breast Center, Iaso Women's Health Hospital, Athens, Greece. 4. Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528, Athens, Greece. florazagouri@yahoo.co.uk.
Abstract
BACKGROUND: Pregnancy-associated breast cancer (PABC) defined as breast cancer diagnosed during gestation, lactation or within 1 year after delivery, represents a truly challenging situation with significantly increasing incidence rate. The genomic background of PABC has only recently been addressed while the underlying mechanisms of the disease still remain unknown. This analysis aims to further elucidate the frequency of PABC cases attributable to genetic predisposition and identify specific cancer susceptibility genes characterizing PABC. METHODS: A comprehensive 94-cancer gene panel was implemented in a cohort of 20 PABC patients treated in our clinic and descriptive correlation was performed among the results and the patients' clinicopathological data. RESULTS: In the present study, 35% of PABC patients tested carried pathogenic mutations in two known cancer predisposition genes (BRCA1 and CHEK2). In total, 30% of the patients carried BRCA1 pathogenic variants. An additional 5% carried pathogenic variants in the CHEK2 gene. Variants of unknown/uncertain significance (VUS) in breast cancer susceptibility genes BRCA2, CHEK2 and BRIP1 were also identified in three different PABC patients (15%). Not all patients carrying germline mutations reported known family history of cancer. CONCLUSIONS: Genetic testing should be considered as an option for PABC patients since the disease is highly associated with genetic susceptibility among other predisposing factors. Germline mutation identification may further modify PABC management approach and improve the prognostic outcome.
BACKGROUND: Pregnancy-associated breast cancer (PABC) defined as breast cancer diagnosed during gestation, lactation or within 1 year after delivery, represents a truly challenging situation with significantly increasing incidence rate. The genomic background of PABC has only recently been addressed while the underlying mechanisms of the disease still remain unknown. This analysis aims to further elucidate the frequency of PABC cases attributable to genetic predisposition and identify specific cancer susceptibility genes characterizing PABC. METHODS: A comprehensive 94-cancer gene panel was implemented in a cohort of 20 PABCpatients treated in our clinic and descriptive correlation was performed among the results and the patients' clinicopathological data. RESULTS: In the present study, 35% of PABCpatients tested carried pathogenic mutations in two known cancer predisposition genes (BRCA1 and CHEK2). In total, 30% of the patients carried BRCA1 pathogenic variants. An additional 5% carried pathogenic variants in the CHEK2 gene. Variants of unknown/uncertain significance (VUS) in breast cancer susceptibility genes BRCA2, CHEK2 and BRIP1 were also identified in three different PABCpatients (15%). Not all patients carrying germline mutations reported known family history of cancer. CONCLUSIONS: Genetic testing should be considered as an option for PABCpatients since the disease is highly associated with genetic susceptibility among other predisposing factors. Germline mutation identification may further modify PABC management approach and improve the prognostic outcome.
Entities:
Keywords:
BRCA1; BRCA2; BRIP1; Breast cancer; CHEK2; Germline mutation; Pregnancy
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