Abstract 153P
Background
Within BRCA carriers, there are data suggesting that not all alterations confer the same risk of breast or ovarian cancer. In addition, the localization of the mutation as a biomarker of response to targeted therapies such as iPARP is in the process of being validated. The distribution of mutations according to the functional domain in which they are located may be a good method for establish their role in cancer risk.
Methods
We included all carriers from the registry of the Hereditary Cancer Unit. Functional domains (dom) of BRCA1 were defined as: Really Interesting New Gene (RING) from aa 8-96; DNA-binding dom (DBD) from aa 452-1092; and BRCA1 C terminal (BRCT) from aa 1650-1863 Functional doms of BRCA2 were defined as: PALB2-BD dom from aa 21-39, RAD51-binding dom (RAD51-BD) from aa 900-2000, and DBD from aa 2459-3190.
Results
284 carriers were located. 66% women, 55% BRCA1 mutation carriers (mc). Of these, 63% healthy carriers (hc), half of whom were women. Among the BRCA1 muts, 55% of breast cancer (bc) were associated with BRCT muts compared with 5.5% in DBD. In the BRCT dom, the mean age at diagnosis (dx) of bc was 44 years, with 35% of luminal tumors. Among hc, only 33% were older than the mean age at dx. Among the BRCA2 muts, 61% of the cases with bc were associated with the RAD51-BD dom compared to 10% in the DBD dom. In the RAD51-BD dom, the mean age at dx of bc was 51 years, with 11% of cases being Her-2 positive and 29% triple negative. Among hc, only 40% were older than the median age at dx. As for ovarian cancer, a more heterogeneous pattern was observed, although again, the doms with the most cases were BRCT and RAD51-BD. Table: 153P
BRCA 1 | BRCA 2 | TOTAL | |||||||||
RING | DBD | BRCT | Others | Total | PALB2-BD | RAD51 | DBD | Others | Total | ||
Healthy carrier | 3 | 21 | 41 | 38 | 103 | 2 | 55 | 5 | 19 | 81 | 184 |
Breast | 1 | 2 | 20 | 13 | 36 | 1 | 17 | 3 | 7 | 28 | 64 |
Ovarian | 1 | 2 | 7 | 8 | 18 | 0 | 6 | 2 | 4 | 12 | 30 |
Pancreas | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 2 | 3 | 4 |
Other tumors* | 0 | 1 | 0 | 0 | 1 | 0 | 6 | 0 | 1 | 7 | 8 |
Total | 5 (3.1%) | 26 (16.4%) | 69 (43.4%) | 59 (37.1%) | 159 | 3 (2.3%) | 85 (64.9%) | 10 (7.6%) | 33 (25.2%) | 131 | 290 |
Mean age at diagnosis | 53 | 63 | 44 | 43.9 | 46 | 51 | 51 | 43 | 49 | 49 | 47 |
*Other tumors: cholangiocarcinoma, medulloblastoma, urotelial, astrocitoma, cervical and melanoma, all with 1 case reported.
Conclusions
The characterization of the mut population can provide data for the personalization of follow-up. In our population, the age of hc is shown as a bias for the definition of risk, so more follow-up and multicenter studies are needed to validate the results.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
186P - Pooled efficacy and safety data of alectinib (A) vs. crizotinib (C) from the randomized phase III ALEX and J-ALEX trials
Presenter: Marco Tagliamento
Session: Poster session 01
187P - Ipatasertib and atezolizumab in cancers with increased PI3K-AKT pathway activity: First results from the CRAFT trial
Presenter: Christoph Heilig
Session: Poster session 01
188P - The landscape of SMARCA2 genomic alterations in Chinese cancer patients
Presenter: Chen Jiaqi
Session: Poster session 01
189P - Design and enrollment for a classifier development study for a blood-based multi-cancer early detection (MCED) test
Presenter: Christopher Douville
Session: Poster session 01
190P - Quantitative serum tumor markers (CEA, CA19-9, and CA-125) are independently predictive of survival in patients with appendiceal adenocarcinoma
Presenter: John Paul Shen
Session: Poster session 01
191P - Novel approach to proficiency testing demonstrates wide gaps in biomarker quality for colon cancer treatment
Presenter: Kassandra Bisson, Brandon Sheffield
Session: Poster session 01
192P - Impact of oncogenic fibroblast growth factor receptor (FGFR) alterations in patients with advanced solid tumors in a real-world setting
Presenter: Hussein Sweiti
Session: Poster session 01
194P - Early kinetics of C-reactive protein for cancer-agnostic prediction of therapy response and mortality in patients treated with immune checkpoint inhibitors: A multi-center cohort study
Presenter: Dominik Barth
Session: Poster session 01
195P - Identification of biomarkers associated with checkpoint inhibitor pneumonitis based on serum proteomic approach and construction of an online interactive visual prediction model
Presenter: Xiaohui Jia
Session: Poster session 01
196P - Serum metabolomics to determine survival of immunotherapy for advanced non-small cell lung cancer: Metabolomic analysis based on two cohorts
Presenter: Yanjun Xu
Session: Poster session 01