Germline PALB2 Mutation in High-Risk Chinese Breast and/or Ovarian Cancer Patients.

Ava Kwong,Hextan Y S Ngan,Karen K L Chan,Cecilia Y S Ho,Aleena Khalid,Vivian Y Shin,Edmond S K Ma,Tsun-Leung Chan,Chun Hang Au

doi:10.3390/cancers13164195

Abstract

Simple SummaryBreast cancer is the most commonly diagnosed cancer in women globally. BRCA1 and BRCA2 mutations are most prevalent in hereditary breast cancer and are associated with increased risk of breast and ovarian cancer. The PALB2 (partner and localizer of BRCA2) mutation was found to be associated with an increased risk of breast cancer and one of the most common mutations, after BRCA1 and BRCA2, in non-BRCA1/2 breast cancer patients. The prevalence of the PALB2 mutation in breast cancer varies across different ethnic groups; hence, it is of intense interest to evaluate the cancer risk and clinical association of PALB2 mutation in Chinese breast and/or ovarian cancer patients. The prevalence of the PALB2 mutation in breast cancer varies across different ethnic groups; hence, it is of intense interest to evaluate the cancer risk and clinical association of the PALB2 mutation in Chinese breast and/or ovarian cancer patients. We performed sequencing with a 6-gene test panel (BRCA1, BRCA2, TP53, PTEN, PALB2, and CDH1) to identify the prevalence of the PALB2 germline mutation among 2631 patients with breast and/or ovarian cancer. In this cohort, 39 mutations were identified with 24 types of mutation variants, where the majority of the mutations were frame-shift mutations and resulted in early termination. We also identified seven novel PALB2 mutations. Most of the PALB2 mutation carriers had breast cancer (36, 92.3%) and were more likely to have family history of breast cancer (19, 48.7%). The majority of the breast tumors were invasive ductal carcinoma (NOS type) (34, 81.0%) and hormonal positive (ER: 32, 84.2%; PR: 23, 60.5%). Pathogenic mutations of PALB2 were found in 39 probands with a mutation frequency of 1.6% and 1% in breast cancer and ovarian cancer patients, respectively. PALB2 mutation carriers were more likely have hormonal positive tumors and were likely to have familial aggregation of breast cancer.

Highlights

IntroductionInherited gene mutation is one of the risk factors for developing breast cancer or ovarian cancer in women
According to studies performed in different populations, PALB2 mutation frequencies in familial breast cancer cases range between 0.6 and 2.7% [1,10,15], while the cumulative average risk reaches approximately 35% by the age of 70, which is similar to the cumulate average risk conferred by germline BRCA2 mutations [1]
Hong Kong Hereditary and High-risk Breast Cancer Registry between 2012 and 2019 with the following selection criteria: (1) had at least one first- or second-degree relative with BRCA-associated cancer, regardless of age; (2) the age at breast cancer diagnosis was under 45 years; (3) bilateral breast cancer; (4) triple-negative breast cancers, (5) cancers with medullary type histology; (6) known to be BRCA mutation related family; (7) male breast cancer

Summary

Introduction

Inherited gene mutation is one of the risk factors for developing breast cancer or ovarian cancer in women. A number of mutations have been identified in hereditary breast cancer, among which BRCA1 and BRCA2 mutations are the most prevalent and associated with increased risk of breast and ovarian cancer [1]. Genetic testing is becoming more important, since the test results greatly impact the clinical management of high-risk patients and their family members. The PALB2 (partner and localizer of BRCA2) mutation was found to be associated with an increased risk of breast cancer and one of the most common mutations, after BRCA1 and BRCA2, in non-BRCA1/2 breast cancer patients [2,3,4,5]. The clinical evidence of PALB2 variants is increasing, and the clinical guidelines and management for PALB2 mutation carriers are mainly based on consensus but still lack solid supportive evidence

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