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
4616 - Alpelisib (ALP) + Endocrine Therapy (ET) by Last Prior Therapy in Patients (pts) With PIK3CA-Mutated Hormone-Receptor Positive (HR+) Human Epidermal Growth Factor Receptor-2-Negative (HER2–) Advanced Breast Cancer (ABC): Additional Study Cohort in BYLieve
Presenter: Eva Ciruelos
Session: Poster Display session 2
Resources:
Abstract
3592 - PRECYCLE: Impact of CANKADO-based eHealth-support on quality of life in metastatic breast cancer patients treated with palbociclib and endocrine therapy.
Presenter: Tom Degenhardt
Session: Poster Display session 2
Resources:
Abstract
4168 - Efficacy and safety of oral poly (ADP-ribose) polymerase inhibitor fluzoparib in patients with BRCA1/2 mutations and platinum sensitive recurrent ovarian cancer
Presenter: Ning Li
Session: Poster Display session 2
Resources:
Abstract
2785 - Effect of response to last platinum-based chemotherapy in patients (pts) with platinum-sensitive, recurrent ovarian carcinoma in the phase 3 study ARIEL3 of rucaparib maintenance treatment
Presenter: Jonathan Ledermann
Session: Poster Display session 2
Resources:
Abstract
3496 - Integrated safety analysis of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in patients (pts) with ovarian cancer in the treatment and maintenance settings
Presenter: Rebecca Kristeleit
Session: Poster Display session 2
Resources:
Abstract
2844 - Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers
Presenter: S.Intidhar Labidi-Galy
Session: Poster Display session 2
Resources:
Abstract
1955 - A Prospective Evaluation of Tolerability of Niraparib Dosing Based on Baseline Body Weight (BW) and Platelet (plt) Count: Blinded Pooled Interim Safety Data from the NORA Study
Presenter: Xiaohua Wu
Session: Poster Display session 2
Resources:
Abstract
2539 - Evaluation of Niraparib 200 mg/d as Maintenance Therapy in Recurrent Ovarian Cancer and Associated Thrombocytopenia in a Real-World US Setting
Presenter: Premal Thaker
Session: Poster Display session 2
Resources:
Abstract
1290 - Niraparib initial dose and its’ management in patients with recurrent high-grade serous ovarian cancer.
Presenter: Jacek Grabowski
Session: Poster Display session 2
Resources:
Abstract
3353 - Results of the 3rd interim analysis of C-Patrol: A non-interventional study on olaparib in German routine clinical practice
Presenter: Jalid Sehouli
Session: Poster Display session 2
Resources:
Abstract