1560P - Optimal age versus real age in breast and gynaecological risk reducing surgery in BRCA1/2 carriers

Background

Both risk reducing mastectomy (RRM) and risk reducing salpingo-oophorectomy (RRSO) are effective strategies for breast and ovarian cancer (BC-OC) prevention in carriers of BRCA1 and BRCA2 pathogenic variants (PVs). The optimal age for RRSO is currently well defined: 35-40 years for BRCA1 and 40-45 years for BRCA2, while the age for RRM is attested around 25-30 years. We investigated these data in an Italian reference center.

Methods

This is a monoinstitutional retrospective study on female carriers of PVs in BRCA1/2 genes, followed at the HBOC Unit at Fondazione IRCCS Policlinico San Matteo, Pavia, from January 2010 to April 2023. Eligible subjects were both healthy carriers of germline PVs in BRCA1 and/or BRCA2 genes who underwent RRM and/or RRSO and patients with a diagnosis of BC or OC. Data were collected in an Excel database and the age at RRM and RRSO, as well as at BC/OC in oncologic patients, was analyzed.

Results

This study includes 542 women: 61.7% with BRCA1 PV, 37.6% with BRCA2 PV and 0.7% with both PVs. • 99 healthy carriers underwent RRM at the mean age of 39.8 years with no difference between BRCA1 and BRCA2 PVs. Within the 296 patients with BC the mean age at disease onset was 40.9 years. Occult BC at the time of RRM was detected in 2% of cases among healthy carriers and in 3% of cases in BC-BRCA. Positive family history for BC was significantly associated with the choice of RRM (p=0,006). • 276 women underwent RRSO at a mean age 47 years in BRCA1 and 49,2 years in BRCA2 PVs. The mean age at diagnosis of OC-BRCA (n=95) was 50.8 years in BRCA1 (n=63) and 58.5 years in BRCA2 (n= 32). Occult OC at the time of RRSO was detected in 7.2% of cases (n=16). Logistic regression model demonstrated that being postmenopausal and parity significantly predicted the choice of RRSO.

Conclusions

In our experience, the real mean age at both RRM and RRSO is higher than recommended by guidelines and scientific evidence in all the settings. This data must be correlated with a late interception of the genetic risk: in 89.4% BC and 74.6% OC the genetic test was performed only after cancer diagnosis. A timely interception of the oncogenetic risk and its adequate management would bring the real age at RRS closer to the optimal age, preventing most of hereditary breast and ovarian cancers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

A. Ferrari.

Funding

aBRCAdabra ETS.

Disclosure

F. Doyle: Other, Personal, Speaker, Consultant, Advisor, scholarship for aBRCAdabra ETS (Italian Advocacy), 2023: AstraZeneca. G. Rizzo: Financial Interests, Personal, Invited Speaker: AstraZeneca. M. Campanella: Financial Interests, Institutional, Funding, as president of Italian advocacy aBRCAdabra ETS: AstraZeneca, GSK, MSD. All other authors have declared no conflicts of interest.