Purpose:Distress and reduced quality of life (QOL) are common among people with cancer. No study has compared these variables after breast cancer diagnosis to pre-cancer diagnosis levels.Methods:Data on women with breast cancer 50 years of age or older (n = 6949) were analyzed from the Women’s Health Initiative (1993–2013). Health-related QOL (physical function, mental health) was measured using Rand-36. Depressive symptoms were measured with the six-item Center for Epidemiologic Studies Depression scale. Assessments occurred before and after the cancer diagnosis. Hierarchical linear modeling compared pre-cancer QOL and depressive symptoms to levels post-diagnosis and tested whether pre-cancer physical activity, stressful life events, sleep disturbance, and pain predicted post-diagnosis outcomes.Results:Compared with pre-cancer levels, depressive symptoms increased (20.0 % increase at 0–6 months, 12.9 % increase at 6–12 months), while physical function (−3.882 points at 0–6 months, −3.545 at 6–12 months) and mental health decreased (−2.899 points at 0–6 months, −1.672 at 6–12 months) in the first year after diagnosis (all p < .01). Depressive symptoms returned to pre-cancer levels after 10 years, but QOL remained significantly lower. At more than 10 years post-diagnosis, physical function was 2.379 points lower than pre-cancer levels (p < 0.01) while mental health was 1.922 points lower (p < 0.01). All pre-cancer predictors were associated with all outcomes. Pain predicted uniquely greater decreases in physical function post-diagnosis.Conclusions:Depressive symptoms increased and QOL decreased following breast cancer diagnosis compared with pre-cancer levels, particularly in the first year.Implications for Cancer Survivors:QOL may remain lower for years after breast cancer diagnosis, although decreases are small.