Abstract 167P
Background
Bilateral breast cancer (BBC) is generally uncommon (1-2.6% of all patients with breast cancer), but its incidence increases particularly by up to 3% in BRCA1 or BRCA2 pathogenic variant (PV) carriers. The aim of our study was to evaluate whether all BBC patients should be offered multi-gene panel testing, regardless the criteria concerning the age at diagnosis, and personal and family history of cancer established by the current guidelines.
Methods
We retrospectively collected and analyzed all clinical information of 150 BBC patients enrolled from October 2015 to April 2021, at the Sicilian Regional Center for the Prevention Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of the Section of Medical Oncology of University Hospital Policlinico “P. Giaccone” of Palermo. Recruited patients have been genetically tested for germline PVs in other gene beyond BRCA1 and BRCA2 by NGS-based multi-gene panel testing.
Results
In our investigation 58 (38.6%) out of 150 BBC patients harbored germline PVs in high and intermediate-penetrance breast cancer (BC) susceptibility genes, including BRCA1, BRCA2, PTEN, PALB2, CHEK2, ATM, RAD51C. Twenty-two out of 58 positively tested patients harbored a PV in a known BC susceptibility gene (no-BRCA). Interestingly, a noteworthy correlation between PVs in PALB2 or CHEK2 and BBCs was observed. In addition, our study showed that CHEK2 PVs are correlated with a luminal A/B phenotype and ATM PVs with a luminal B subtype. In conclusion, we found that, in the absence of an analysis performed via multi-gene panel, a significant proportion (14.7%) of PVs in genes different from BRCA1/2 would have been lost.
Conclusions
Our investigation led us to hypothesize that a deeper genetic analysis, through NGS-based multi-gene panel testing, could increase the detection rates of germline alterations in BBC patients. Particularly, in the near future, the evaluation of PVs could help to identify family members with a greater risk of developing BC (or other tumors) and consequently implement prevention and surveillance programs for these subjects.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University-Hospital Policlinico \"Paolo Giaccone\", Palermo, Italy.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.