Abstract 5612
Background
Pathogenic germline BRCA1/2 mutations are found in higher rates in patients with triple negative breast cancer (TNBC). As a result, genetic BRCA mutation testing would be beneficial for this particular group of patients. At the same time, it is less clear if mutational burden in other cancer predisposition genes is more frequent in TNBC and has to be recommended for genetic testing. In the current study we aimed to characterize pathogenic germline mutations in TNBC patients fulfilling NCCN criteria of hereditary cancers from Russian Federation.
Methods
Individuals with diagnosis of TNBC were selected to be included in this study according based on the following criteria: (1) young age of disease onset, (2) the presence of relatives with breast or ovarian cancer diagnosis. The NimbleGen SeqCap EZ Choice kit (“Roche”) was used for target enrichment, and sequencing was performed using Illumina MiSeq (“Illumina”). Custom bioinformatic pipeline, including Annovar, HGMD Professional 2017.4 and BIC databases were used to identify pathogenic mutations.
Results
128 patients with triple negative breast cancer aged from 24 to 79 years old were included in this study. 42 woman has their first cancer diagnosis before 40 years old, 77 – between 41 and 60 years old, 9 - were older than 60. 42 patients (33%) carried pathogenic or likely pathogenic variant in BRCA1 gene,10 (8%) in BRCA2 gene and 40 (31%) in one of other genes, including BUB1, CDH1, CDKN2A, CHEK2, EPCAM, FANCI, MLH3, MSH6, PALB2, PMS2, POLE, POLE, RAD50, RBBP8, RET, STK11, APC, ATM, BARD1, BLM. 13 woman had double mutation in two genes, and one patient had double mutation in BRCA1 gene. For the BRCA1 carriers subgroup, the median age at diagnosis was 41(24-64), BRCA2 carriers – 44 (27-62) and other genes carriers – 48 (28-79) year old. Patients with double mutation had median age of cancer manifestation at 42 (32-65).
Conclusions
Approximately 38% of patients with TNBC fulfilling NCCN criteria of hereditary cancer are carriers of pathogenic and likely pathogenic mutations in BRCA1 and BRCA2 genes. And up to 40% - in other cancer susceptibility genes. Thus, the patients with TNBC might be recommended for extended genetic testing depending on age of onset and the presence of a cancer family history.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Tatarstan Cancer Center.
Funding
The work is supported by Russian Foundation for Basic Research № 18-415-160009 and according to the Russian Government Program of Competitive Growth of Kazan Federal University.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5792 - A novel PET parameter for cancer stem cell metabolism: early prediction of chemosensitivity to neoadjuvant chemotherapy in locally advanced breast cancer
Presenter: Chanwoo Kim
Session: Poster Display session 2
Resources:
Abstract
3728 - Using nodal ratio to predict recurrence in patients with 4 or more positive lymph nodes early stage breast cancer
Presenter: Besma Graja
Session: Poster Display session 2
Resources:
Abstract
3395 - Re-sentinel node biopsy for local recurrence after breast-conserving surgery
Presenter: Yuka Matsubara
Session: Poster Display session 2
Resources:
Abstract
4302 - Assessment of prognostic and therapeutic factors in men with breast cancer
Presenter: Daniel Herrero Rivera
Session: Poster Display session 2
Resources:
Abstract
4263 - Genomic Profiling of Chinese Breast Cancer Patients
Presenter: Zhonghua Tao
Session: Poster Display session 2
Resources:
Abstract
2406 - Genome copy number alteration burden represents predictor of response in long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer
Presenter: Naomi Walsh
Session: Poster Display session 2
Resources:
Abstract
2575 - Next-generation DNA Sequencing (NGS) Results for Tumors From Phase 2 ABRAZO Study of Talazoparib After Platinum or Cytotoxic Non-Platinum Regimens in Patients (pts) With Advanced Breast Cancer (ABC) and Germline BRCA1/2 (gBRCA) Mutations
Presenter: Nicholas C. Turner
Session: Poster Display session 2
Resources:
Abstract
4499 - FGFR1 and CCND1 gene amplifications are associated with breast cancer resistance to aromatase inhibitors
Presenter: Evgeny Imyanitov
Session: Poster Display session 2
Resources:
Abstract
4110 - Clinicopathologic features of BRCA mutated breast cancer patients: Hacettepe Experience
Presenter: Sercan Aksoy
Session: Poster Display session 2
Resources:
Abstract
5203 - Novel fusion genes identified from matched primary and recurred breast cancers by RNA-sequencing
Presenter: Soojeong Choi
Session: Poster Display session 2
Resources:
Abstract