Abstract 1687
Background
Although Brazilian publications on BRCA mutations predisposing to breast/ovarian cancer have increased in the last five years, the genetic Background of this population is still underrepresented. Mostly, screening has been performed in patients from south-southeast states who met the NCCN guidelines. We present a cohort of breast/ovarian cancer patients, in a private laboratory with a wide market capillarity, where a subset of patients without strict criteria may have access to the test on medical request.
Methods
A total of 1,284 consecutive patients were referred for molecular screening to a private laboratory between January 2017-March 2019. Next-generation sequencing and multiplex ligation-dependent probe amplification (MLPA) for BRCA1/2 genes were performed for all patients, except for 15 that were evaluated only by MLPA. Bioinformatic tools with specific algorithms for variant calling and annotation were employed.
Results
Pathogenic germline variants were identified in 12% (n = 156) of patients: 61% in BRCA1 and 39% in BRCA2. To our knowledge, 25 BRCA2 and 17 BRCA1 germline mutations have not been previously described in Brazilian reports. Frameshift and nonsense alterations were the most prevalent types (52% and 22%, respectively). While sixty non-recurring mutations were identified, 31 in BRCA1 and 29 in BRCA2, eleven pathogenic variants were detected 3 or more times, 7 BRCA1 and 4 BRCA2. In agreement with previous reports, c.5266dupC, c.3331_3334delCAAG (BRCA1) and c.2808_2811delACAA (BRCA2) were the most frequent variants. One large rearrangement (deletion of exons 15-16) and the Portuguese founder Alu insertion, c.156_157insAlu, both in BRCA2, were also detected. Additionally, three BRCA1 (c.5074 + 1delG; c.131_132delGC; c. 4414delC) and five BRCA2 (c.6407T>G, c.3659dupA, c.3601_3602delinsT, c.8682delA; c.4329delT) novel mutations were observed.
Conclusions
Our results confirm the reported molecular heterogeneity of Brazilian patients, highlighting the identification of 8 germline pathogenic variants not yet described in BRCA 1/2 reference databases. The detected mutations were associated to a vast array of ethnicities, confirming the admixture of Brazilian population.
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
3911 - Defining a SUV decrease cut-off in PET/CT response monitoring after one cycle of preoperative breast cancer chemotherapy
Presenter: Marcin Kubeczko
Session: Poster Display session 2
Resources:
Abstract
1849 - Effect of thioredoxin 1 quantity detection to complement the mammography in breast cancer diagnosis
Presenter: Younju Lee
Session: Poster Display session 2
Resources:
Abstract
2221 - Identification of ultralow risk breast cancer patients (probable overdiagnosis)
Presenter: Salvador Gamez Casado
Session: Poster Display session 2
Resources:
Abstract
5291 - Prevalence of Vitamin D3 deficiency among women with early breast cancer receiving chemotherapy in an oncology dayward.
Presenter: Warner Finstad
Session: Poster Display session 2
Resources:
Abstract
4247 - Changes in ER pathway activity score during neoadjuvant letrozole to assess therapy response and predict disease free survival (DFS) in ER positive breast cancer patients
Presenter: Arran Turnbull
Session: Poster Display session 2
Resources:
Abstract
568 - Second primary malignancies in patients with breast cancer.
Presenter: Carlos Erasun Lecuona
Session: Poster Display session 2
Resources:
Abstract
1428 - Phase II randomized trial of neoadjuvant trastuzumab and pertuzumab (TP) with either palbociclib + letrozole (Pal+L) or paclitaxel (Pac) for elderly patients with estrogen receptor & HER2 positive (ER+/HER2+) Breast Cancer (BC) (International Breast Cancer Study Group IBCSG 55-17, TOUCH)
Presenter: Laura Biganzoli
Session: Poster Display session 2
Resources:
Abstract
1479 - Neoadjuvant HER2-targeted therapy with or without immunotherapy with pembrolizumab (neoHIP): an open label randomized phase 2 trial
Presenter: Heather McArthur
Session: Poster Display session 2
Resources:
Abstract
1481 - A randomized phase 2 study of peri-operative ipilimumab, nivolumab and cryoablation versus standard care in women with residual, early stage/resectable, triple negative breast cancer after standard-of-care neoadjuvant chemotherapy
Presenter: Heather McArthur
Session: Poster Display session 2
Resources:
Abstract
4334 - ALEXANDRA/IMpassion030: A phase 3 study of standard adjuvant chemotherapy with or without atezolizumab in early stage triple negative breast cancer.
Presenter: Michail Ignatiadis
Session: Poster Display session 2
Resources:
Abstract