Abstract Background: Having a family history of breast or ovarian cancer is an important risk factor for premenopausal breast cancer. One reason for this could be that women with an underlying genetic susceptibility are more sensitive to environmental exposures due to gene-environment interactions. This might be especially important if the exposure occur during windows of susceptibility, such as pregnancy. Aim: The aim of this project is to determine if exposure to air pollution during pregnancy is associated with premenopausal breast cancer in a population with a known family history of breast or ovarian cancer. Methods: The project is based on nation-wide data from Sweden’s national registers and utilizes a cohort study design. The original cohort consists of women who gave birth to their first child between 1992 and 2015 (n=1 074 925), from this cohort we will select women with at least one first degree relative with breast or ovarian cancer (confirmed through register linkage). The primary outcome is primary breast cancer diagnosed before 50 years of age, and the exposure is levels of air pollution (PM10, PM2.5 and NO2) at the participant’s home address during each pregnancy. Cox proportional hazards regression will be used to determine hazard ratios using age as the time-scale. Results: The registry based linkage makes it possible to distinguish between both relational context (mother or sister), number of afflicted first degree relatives and type of cancer (breast or ovarian). All included women also have at least one recorded pregnancy (prior to any cancer diagnosis). Conclusion: This large scale study will be able to provide important information about the impact of air pollution exposure during pregnancy on breast cancer risk in a population with a documented family history of breast or ovarian cancer. Citation Format: Anna Hettinger, Jessica Edlund, Malin Gustafsson, Jenny Lindén, Wendy Yi-Ying Wu, Anna Oudin, Sophia Harlid. Air pollution exposure during pregnancy and risk of premenopausal breast cancer among women with a family history of cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4215.