A systematic literature review was conducted to determine whether physical activity levels during adolescent and young adult years were associated with a reduced lifetime risk of breast cancer among carriers of deleterious mutations in BRCA1 and BRCA2 genes. Ovid/MEDLINE, Embase, CENTRAL, WOS, and CINAHL were searched for articles including information about adolescent and young adult physical activity and breast cancer incidence among women carrying deleterious BRCA1 and BRCA2 gene mutations (search was initiated in October 2019; last update and full analyses were in March 2021). Independent reviewers screened articles at the title/abstract and full-text levels, resolving differences by consensus with lead authors. The NIH Quality Assessment Tools were used to assess sources of bias. A total of 1,957 unique articles were identified; 5 met inclusion criteria. Samples size ranged from 68 to 1,185. All studies relied on self-reported adolescent and young adult physical activity. One study measured sports involvement; the others measured recreational activity. One large study was null, whereas 4 others showed a reduction in breast cancer incidence later in life with higher adolescent and young adult physical activity (p≤0.05). However, the protection was limited to premenopausal breast cancer in 1 of the studies (OR=0.62; 95% CI=0.40, 0.96; p-trend=0.01). In addition, adolescent and young adult physical activity was associated with older age at breast cancer diagnosis in 1 study (p=0.03). A limited number of studies suggest that adolescent and young adult physical activity may reduce or delay the risk of breast cancer incidence among carriers of deleterious mutations in BRCA1 and BRCA2 genes.