OBJECTIVE: To study the association between breast cancer and work burden over 25 years. METHODS: The study was based on the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) cohort (n = 14,220) and included women who had answered the questionnaire from the year 1994 and had no previous breast cancer. Breast cancer cases were recorded from the Finnish Cancer Registry during the study period: from 1st June 1994 till December 31, 2019. Using questionnaires, we collected information on work burden, body mass index (BMI), menopausal hormone therapy (MHT), alcohol consumption, parity, and family history of breast cancer. Work burden was categorized as low or high. Variables were used both in the univariate and multivariate Cox regression analyses to explore their associations with breast cancer. RESULTS: Altogether 825 women (6.9%) were diagnosed with breast cancer during the study period with a mean follow-up of 13.3 ± 7.2 years. Women with breast cancer were compared to those without breast cancer during the follow-up period (n = 11,117). A low work burden was associated with a 1.3-fold higher incidence of breast cancer (95% confidence interval 1.2-1.6) than a high work burden. Low work burden was associated with an increased breast cancer risk. CONCLUSION: Low work burden is associated with elevated postmenopausal breast cancer risk in the 25-year follow-up period.