Abstract 103P
Background
Triple-negative breast cancer (TNBC) patients (pts) are at increased likelihood of carrying a BRCA pathogenic variant. Clinical testing guidelines recommend BRCA genetic testing for TNBC pts aged 60 years or younger, independently from family history. We here aim to determine rate of BRCA pathogenic variants according to family and personal history in a large cohort of TNBC pts from Northern Italy.
Methods
Pts diagnosed with TNBC < 60 years of age in the North-East Italy who underwent BRCA 1/2 germline mutation testing at the Istituto Oncologico Veneto between January 2013 and April 2021 were included. Pts were categorized according to personal/family history in 4 groups: 1: HBC/HBOC (hereditary BC or hereditary breast-ovarian cancer; at least 3 first-grade cases of BC – or 2 BC cases and 1 ovarian cancer case – with at least one BC < 40 years of age or bilateral); 2: personal history of TNBC and either of the following: early onset BC <36 years of age, bilateral BC < 50 years of age, ovarian cancer; 3: less stringent family history criteria; 4: sporadic TNBC (absence of family history and exclusion from group 2).
Results
We identified 532 TNBC pts < 60 years of age, with 96 pts (18%) diagnosed with BRCA1/2 pathogenic mutations. Distribution of patients according to personal/family history was as follows: Group 1 (HBC/HBOC) n=94; group 2 (personal history indicating BRCA-testing) n=77; group 3 (weaker family history of BRCA-related cancers) n=123; group 4 (sporadic TNBC) n=238. The rate of BRCA1/2 positivity progressively decreased across the four groups. In particular, the rate of BRCA1/2 positivity was 48% in group 1, 26% in group 2, 14% in group 3 and 6% in group 4 (p<0.0005).
Conclusions
BRCA 1/2 mutation rate was significantly lower in sporadic TNBC than in other TNBC showing at least some degree of familial history. Our results highlight the importance of personal and family history in determining the risk of germline BRCA 1/2 mutation in TNBC < 60 years of age. These data might be useful to prioritize access to test, also in view of the increasingly relevant role of the BRCA1/2 mutations in the choice of the therapeutic strategies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Zovato: Financial Interests, Institutional, Advisory Board: Eisai; Financial Interests, Institutional, Advisory Board: Lilly. G. Griguolo: Financial Interests, Personal, Other, travel grant: Pfizer; Financial Interests, Personal, Other, travel grant: Novartis; Financial Interests, Personal, Other, Travel grant: Amgen; Financial Interests, Personal, Other, travel grant: Daiichi. M.V. Dieci: Financial Interests, Personal, Advisory Board, outside the submitted work: Eli Lilly; Financial Interests, Personal, Advisory Board, outside the submitted work: Novartis; Financial Interests, Personal, Advisory Board, outside the submitted work: Novartis; Financial Interests, Personal, Invited Speaker, outside the submitted work: Eli Lilly; Financial Interests, Personal, Invited Speaker, outside the submitted work: Pfizer; Financial Interests, Institutional, Research Grant, outside the submitted work: Veneto Institute of Oncology IOV - IRCCS; Financial Interests, Institutional, Research Grant, outside the submitted work: Italian Ministry of Health; Financial Interests, Institutional, Research Grant, outside the submitted work: University of Padova. G. Crivellari: Financial Interests, Institutional, Advisory Board: Eisai; Financial Interests, Personal, Ownership Interest: Novartis; Financial Interests, Personal, Ownership Interest: Roche. P.F. Conte: Financial Interests, Personal, Advisory Board, outside the submitted work: Novartis; Financial Interests, Personal, Advisory Board, outside the submitted work: Eli Lilly; Financial Interests, Personal, Advisory Board, outside the submitted work: AstraZeneca; Financial Interests, Personal, Advisory Board, outside the submitted work: Tesaro; Financial Interests, Personal, Other, honoraria outside the submitted work: BMS; Financial Interests, Personal, Other, honoraria outside the submitted work: Roche; Financial Interests, Personal, Other, honoraria outside the submitted work: Eli Lilly; Financial Interests, Institutional, Research Grant, outside the submitted work: novartis; Financial Interests, Institutional, Research Grant, outside the submitted work: Roche; Financial Interests, Institutional, Research Grant, outside the submitted work: BMS; Financial Interests, Institutional, Research Grant, outside the submitted work: Merck-KGa; Financial Interests, Institutional, Research Grant, outside the submitted work: Italian Ministry of Health; Financial Interests, Institutional, Research Grant, outside the submitted work: Veneto Secretary of Health; Financial Interests, Institutional, Research Grant, outside the submitted work: University of Padova. V. Guarneri: Financial Interests, Personal, Invited Speaker, outside the submitted work: Eli Lilly; Financial Interests, Personal, Advisory Board, outside the submitted work: Eli Lilly; Financial Interests, Personal, Advisory Board, outside the submitted work: MSD; Financial Interests, Personal, Advisory Board, outside the submitted work: Novartis; Financial Interests, Personal, Invited Speaker, outside the submitted work: Novartis; Financial Interests, Personal, Advisory Board, outside the submitted work: Roche; Financial Interests, Institutional, Principal Investigator, local PI; outside the submitted work: AstraZeneca; Financial Interests, Institutional, Principal Investigator, local PI; outside the submitted work: BMS; Financial Interests, Institutional, Principal Investigator, local PI; outside the submitted work: Eli Lilly; Financial Interests, Institutional, Principal Investigator, local PI; outside the submitted work: MSD; Financial Interests, Institutional, Principal Investigator, local PI; outside the submitted work: Novartis; Financial Interests, Institutional, Principal Investigator, local PI; outside the submitted work: Roche; Financial Interests, Institutional, Principal Investigator, local PI; outside the submitted work: Synton Biopharmaceuticals. All other authors have declared no conflicts of interest.