Germline Mutations in a Clinic-based Series of Pregnancy Associated Breast Cancer Patients

Abstract

Background: Pregnancy-associated breast cancer (PABC) defined as breast cancer diagnosed during gestation, lactation or within one 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 offered to PABC patients regardless of family history as the disease is highly associated with genetic predisposition. Germline mutation identification may further modify PABC management approach and improve the prognostic outcome.

Clinicopathologic features, treatment, and prognosis of pregnancy-associated breast cancer

“…Azim et al (20)draw the same conclusion, and they also found that the expression of two particular pathways was significantly enriched in PABC group: the G-protein coupled receptor pathway (GPCR) and the serotonin receptor signaling pathway. Zografos et al (21)observed that among a cohort of 20 PABC patients, 35% of PABC patients tested carried pathogenic mutations in BRCA1 and CHEK2 genes. Some patients carrying germline mutations did not report a family history of cancer (21).Thus, highlighting the genomics of PABC and examining all biological pathways will further facilitate the identification of novel biomarkers defining women who are at high risk of developing PABC in the general population (18,22).…”

“…Zografos et al (21)observed that among a cohort of 20 PABC patients, 35% of PABC patients tested carried pathogenic mutations in BRCA1 and CHEK2 genes. Some patients carrying germline mutations did not report a family history of cancer (21).Thus, highlighting the genomics of PABC and examining all biological pathways will further facilitate the identification of novel biomarkers defining women who are at high risk of developing PABC in the general population (18,22). BC-PP is also more unfavorable, as the rate of HER-2 positive and Ki-67≥20% was significantly higher than that of its controls (P=0.01, 0.018, respectively), although age, year of diagnosis, and TNM stage were well matched.…”