Abstract Introduction: There are several reports of an earlier age of diagnosis in successive generation among BRCA1/2 mutation carriers' families, which may indicate an anticipation phenomenon among hereditary breast cancer (BC) patients. Here, we assess for evidence of anticipation, by evaluating trends in age at diagnosis and phenotype of BC across two successive generations pairs of BRCA1/2 mutation carriers and non-carriers with BC. Methods: The study retrospective cohort was extracted from the oncogenetic database of the Sharett Institute of Oncology (established in 1995), Hadassah Medical Center (N=14,450). Patient characteristics and pathological data were collected from the oncogenetic database, from patients' medical files and pathological reports and compared using independent student's t-test and chi-square tests. Survival analysis was carried out in order to compare survival rates between mothers (M) and daughters (D) and between carriers and non-carriers. Results: The final study cohort includes 126 patients that forms 67 pairs of M and D, both diagnosed with BC and genetically tested for BRCA1/2 mutations. Among M, 35 were BRCA carriers (52%) and 35 were BRCA carriers in the D group (52%). Several patients' characteristics (table 1) were different between M & D. Age at diagnosis of all BRCA carriers was significantly younger in all BRCA carriers vs. wildtype. Moreover, age at diagnosis was significantly younger in D vs. M, in both groups of BRCA carriers and non-carriers. In addition, age at first pregnancy was significantly younger in M vs. D in both groups. Furthermore, tumor phenotype was also different; BRCA carriers had more invasive ductal histology vs. non-carriers, (94% vs. 80%, p=0.024), more triple negative BC, (40% vs. 6%) and more grade 3 BC (60% vs. 18%, P=0.001). Survival analysis revealed significantly better outcomes for D vs. M among BRCA1/2 carriers with triple-negative BC (5-year survival of 91% and 75%, respectively). Conclusions: Breast cancer appeared to be diagnosed at an earlier age in successive generation among BRCA mutation carriers and non-carriers. This observation could be attributed to gene-environment interactions. The fact that we also observed a downshift at age of diagnosis in non-carriers mothers and daughters, emphasizes that other factors (environmental, life style or social) may influence the age at diagnosis. Significantly better survival among second generation of BRCA carriers in triple negative BC can be attributed mainly to better therapy. Further studies are warranted to explore the younger age of the second generation at presentation, and additional means to further improve outcome. Table 1- Patient's CharacteristicsBRCA1/2 carriers BRCA non-carriersParameterMotherDaughterP valueMotherDaughterP valueAge at diagnosis of BC48.2337.38<0.00160.745.2<0.001Age at first period13.5213.250.4613.212.60.24Age of last period47.4440.540.00150.542.10.026Age at first pregnancy22.924.950.082326.50.022Number of pregnancies4.783.250.024.84.20.5 Citation Format: Aviya Kedmi, Luna Kaduri, Albert Grinshpun, Shiri Shkedi, Vardiella Meiner, Tamar Hamburger, Ofra Maimon, Tamar Peretz. Genetic anticipation among BRCA1/2 mutation carriers with breast cancer [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 P5-08-12.