Study on clinical characteristics of PALB2 gene-related breast cancer / 肿瘤研究与临床

ABSTRACT

Objective:To explore the clinical characteristics of breast cancer patients with PALB2 gene mutation.Methods:Data of 2030 female patients with early-stage breast cancer admitted to the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College from July 2015 to July 2019 were retrospectively analyzed, and the patients were all from Genetic Investigation of Inherited & Familial Tumor Syndrome study cohort (GIFTS study, clinical trial registration number: ChiCTR1900024050). All these patients underwent the panel-based next-generation sequencing (NGS) on all the exons 50 cancer predisposition genes including BRCA1, BRCA2, PALB2, etc. The patients were divided into the PALB2 gene mutation group and the non-mutation carriers group according to the results of genetic testing. Furthermore, the clinicopathological characteristics were compared between the two groups, and their compliance of the National Comprehensive Cancer Network (NCCN) genetic testing criteria were also evaluated.Results:Among 2 030 patients with breast cancer, 184 patients (9.06%) harbored pathogenic germline variants, including 22 cases (1.08%) with PALB2 gene mutation and 1 666 cases (82.07%) without gene mutation. Patients with PALB2 gene mutation were at younger ages of onset than the non-mutation carriers group [(39±7) years old vs. (43±9) years old, t = -2.40, P = 0.016] and had higher proportion of early-onset breast cancer (age of onset < 35 years old) than the non-mutation carriers group [31.82% (7/22) vs. 14.83% (247/1 666), χ2 = 4.90, P = 0.036]. Patients with PALB2 gene mutation presented more positive family histories of pancreatic cancer than the non-mutation carriers group [9.09% (2/22) vs. 1.44% (24/1 666), χ2 = 8.38, P = 0.044], higher proportion of histological grade Ⅱ [85.00% (17/20) vs. 61.25% (811/1 324), χ2 = 4.70, P = 0.036], more hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative patients [86.36% (19/22) vs. 63.53% (1 040/1 637), χ2 = 4.90, P = 0.026], and less HR-positive and HER2-positive patients [0 (0) vs. 16.62% (272/1 637), P = 0.037]. Among 22 patients with PALB2 gene mutation, 18 (81.82%) met the NCCN genetic testing criteria for hereditary breast cancer; among 1 666 patients without gene mutation, 1 166 (69.99%) met the NCCN genetic testing criteria for hereditary breast cancer, and the difference was not statistically significant ( χ2 = 1.45, P = 0.347). Conclusions:The Chinese patients with PALB2 gene-related breast cancer have shown distinct clinical characteristics and genetic etiology. However, a more accurate screening criterion for identifying hereditary breast cancer is still needed in clinical practice.