Abstract Background: Air pollution has been linked to an increased risk of breast cancer, but most previous studies have not considered if the exposure occurred during windows of susceptibility, such as pregnancy. Pregnancy is a period of rapid changes to both the breast tissue and the surrounding microenvironment. Exposures during this sensitive time-period could therefore result in erosion of the protective effect of pregnancy and make women more susceptible to external breast cancer risk factors. Aim: The aim of this study was to identify associations between air pollution exposure, occurring specifically during pregnancy, and risk of premenopausal breast cancer. Method: Using nation-wide data from Swedish registers we constructed a cohort consisting of all women in Sweden who gave birth to their first child between January 1st 1991 and December 31st 2015. Women with a cancer diagnosis prior to pregnancy were excluded. Data on air pollution (yearly averages of PM10, PM2.5 and NO2), was collected from the residence of women during, and to some extent between, pregnancies. Associations between air pollution and premenopausal breast cancer is evaluated using Cox proportional hazards regression to estimate hazard ratios (HR), using age as the time scale and including appropriate confounders such as socioeconomic variables, comorbidities and family history of breast or ovarian cancer. Results: The full cohort included 1 074 925 unique women and 2 302 256 pregnancies (the mean number of pregnancies for each woman was 1.75). During the study period, 13 292 (1.2 %) were diagnosed with breast cancer before they turned 50 years. Conclusion: Our working hypothesis is that women exposed to higher levels of air pollution during pregnancy will have a higher risk of breast cancer. This large-scale study will have enough statistical power to detect the effect of air pollution on breast cancer risk, taking into account exposure both during and between pregnancies. Citation Format: Jessica Lena Edlund, Malin Gustafsson, Jenny Linden, Wendy Yi-Ying Wu, Anna Oudin, Sophia Harlid. Exposure to air pollution during pregnancy and risk of premenopausal breast cancer: A Swedish nation-wide cohort study including more than 1 million women. [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 4214.