BACKGROUNDGenetic anticipation refers to the earlier onset of breast cancer (BC) in successive generations, is underreported in Asian populations. This study investigates the phenomenon in Pakistani familial BC patients.METHODSThe study analyzed 171 mother-daughter BC pairs, including BRCA1 (n = 52), BRCA2 (n = 11) pathogenic variant (PV) carriers, and non-carriers (n = 108). Additionally, 741 first-degree female relatives of the mothers and daughters, affected (n = 96) or unaffected (n = 645) with BC, were included. Ages at BC diagnosis in mother-daughter pairs were compared using a paired t-test, while differences in BC occurrence between daughters' and mothers' generations were assessed using odds ratios (ORs).RESULTSDaughters were diagnosed with BC significantly earlier than their mothers, with intergenerational age differences of 14.3 years in BRCA1 (33.7 vs. 48.0; P < 0.0001), 11.5 years in BRCA2 (37.4 vs. 48.9; P < 0.0001) PV carriers, and 12.6 years in non-carriers (41.3 vs. 53.9; P < 0.0001). This difference was independent of birth cohort effects and ascertainment bias. While BC incidence was 20 % higher in the mothers' generation compared to the daughters' generation (42.7 % vs. 38.3 %; OR 1.20, 95 % CI 0.94 - 1.53; P = 0.135), the difference was not statistically significant. Survival durations between generations were also comparable (4.49 years vs. 3.94 years; P = 0.465).CONCLUSIONThis first study on anticipation effect in Pakistani familial BC patients demonstrates significantly earlier BC onset in daughters than in mothers, irrespective of BRCA1/2 PV carrier status. These findings highlight the need to refine BC screening guidelines for high-risk Pakistani populations.