Abstract PURPOSERecent studies questioned the role of BRCA2 as a prognostic factor. Although differences between clinicopathological characteristics of BRCA1-breast cancer (BC) and BRCA2-BC have been described, long-term follow-up data related to prognosis and survival is lacking. We report the analysis of our cohort of BRCA1/2-BC patients (pts) included in our multidisciplinary program. This cohort includes BRCA2-BC c.156_157insAlu carriers, which was previously described as a Portuguese founder mutation. PATIENTS AND METHODS All pts underwent comprehensive BRCA1/2 testing. Data was obtained from all BRCA1/2 pts included in prospective follow up from January 2000 to June 2019, with BC as first cancer diagnosis. Follow-up started after genetic testing. RESULTSFrom 5504 cases (4021 index, 1483 family relatives) that consented on BRCA1/2 testing, 613 BRCA1/2 were cancer pts, of which 478 (78%) had BC as their first cancer diagnosis. These were mostly BRCA2 (n=321, 67.2% vs BRCA1 n=156, 32.6%) females (95.2%), and 129 (40%) of all BRCA2 cases were 156_157insAlu. Three pts had double pathogenic mutations (BRCA1+CHEK2, BRCA2+CHEK2 and BRCA1+BRCA2). Median follow-up was 4.3 yrs (0-17.8).Median age at testing was 50.3 (21-84) yrs and median age at BC diagnosis was significantly higher for BRCA2-BC (45.9 (21-80) vs 42.7 yrs (28-65), p<0.02) than for BRCA1-BC. Compared to BRCA1 pts, BRCA2 pts had higher prevalence of tumors <1cm at diagnosis (10.6% vs 5.8%, p=0.057), hormone receptor positive status (60.4% vs 28.8%, p<0.0001), and lower prevalence of TN phenotype (9.3% vs 48.7%, p<0.0001). BRCA2-BC was associated with longer median time to relapse (TTR) (63.6m, 95% CI 43.1-84.2, vs 23.3m, 95% CI 18.6-28.5, p<0.05), even if relapse rates were similar (9.9% vs 9.6%) and, for a median follow up of 4.3 yrs, no statistically significant difference for survival was observed (7.2 yrs (95% CI 4.1-10.3) vs 5.9 yrs (95% CI 3.8-7.9) for BRCA2-BC and BRCA1-BC respectively).Uptake of preventive surgeries (bilateral or contralateral mastectomy*, adnexectomy, or both) was similar between both groups (BRCA2 17.8%, 27.1% and 11.5% vs BRCA1 18.6%, 26.9% and 10.9%, respectively). Subsequent cancers occurred in 169 pts (35.4%), and were mostly BC (BRCA2 69.1% vs BRCA1 58.7%). Having subsequent cancer was associated with BRCA2 status (72.8% vs 27.2%, p<0.04), not undergoing risk-reducting mastectomy (91.7% vs 8.3%, p<0.0001) and not undergoing risk-reducting mastectomy with bilateral anexectomy (95.3% vs 4.7%, p=0.001). Regarding subsequent cancers, 116 cases were detected during prospective follow-up, 89 in 66 BRCA2-BC and [CB1] 27 cancers in 27 BRCA1-BC. CONCLUSIONIn our population, there is a higher prevalence of BRCA2-BC than BRCA1-BC, not completely explained by the founder effect of c.156_157insAlu. For the described follow up, TTR was longer for BRCA2-BC pts but survival was not different between the two groups, even though BRCA2 status was associated with more subsequent cancer diagnoses. As expected, preventive surgeries were inversely associated with second cancers. Data on prognosis and survival needs to be confirmed with longer follow up. *- includes pts previously treated with conservative surgery Citation Format: Catarina Bexiga, Priscila Nejo, Inês Oliveira, Paula Rodrigues, Patrícia Pereira, Sofia Fragoso, Alexandra Mayer, Joana Parreira, Sidónia Santos, Pedro Louro, Ana Luís, Sandra Bento, Isália Miguel, Cecília Moura, Ana Clara, Fátima Vaz. When BRCA2-breast cancer is more prevalent than BRCA1-breast cancer: Prospective follow-up data from a multidisciplinary program [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-17.