Impact of BRCA1/2 gene mutations on survival of patients with pancreatic cancer: A case-series analysis

Abstract

BRCA gene mutations are found in up to 10% of pancreatic adenocarcinoma cases. We present a description of 4 cases along with a review of the current literature regarding pathogenesis, target treatment, response and survival rates in these types of malignancies. We describe four cases of pancreatic adenocarcinoma, in three of which the BRCA2 mutation was identified, in one - BRCA1 gene alteration. Two patients underwent surgery following the neoadjuvant treatment with Folfirinox and radiotherapy; in the first case, a distal pancreatectomy with splenectomy was performed and in the second one - the Whipple's procedure. In both cases, a complete pathological response was reported. Other 2 patients were treated with Folfirinox after BRCA mutation identification and acceptable life expectancy was obtained. The association of pathologic complete response (PCR) with lower rates of local recurrence and better survival in patients with various types of adenocarcinomas is well known. Identification of such patients carrying BRCA mutations could provide an application of better personalized treatment. In some patients with pancreatic cancer, especially when there is clinical or demographic reason to suspect a genetic predisposition, a confirmation of the presence of BRCA mutations could provide an opportunity to use target treatment with beneficial outcomes regarding survival.

Keywords: BRCA mutations; Cisplatin; Folfirinox; Pancreatic adenocarcinoma; Pathologic complete response.

Fig. 1. Axial magnetic resonance imaging (MRI) images before (right) and after (left) the therapy in the neck of pancreas (red arrow), marked tumor shrinkage after neoadjuvant chemoradiation is indicated with the arrow on the second MRI-scan.

Fig. 2. Intraoperative findings (fibrosis) in the specimen.

Fig. 3. Microphotograph images of complete tumor response with absence of tumor cells that are replaced by extensive quantities of mucus and reparative mesenchymal cells (×2).

Fig. 4. BRCA deficient cells are more sensitive to DNA cross-linking agents such as cisplatin. hR, homologous recombination; dsB, double strand breaks [from Sonnenblick et al., 2011].