Breast Cancer Prevention – lifestyle modifications or targeted interventions?

Abstract: Breast cancer is now the most frequently diagnosed cancer in the world. Breast cancer prevention has gained increasing attention due to increasing breast cancer incidence rates in the West and can be actualized through lifestyle modifications or targeted interventions. Mammographic breast density (MBD) is a well-established independent breast cancer risk factor that is not well-understood on a molecular level. The aim of this thesis work was to offer further insight to breast cancer prevention with a special focus on mammographic breast density.We first investigated physical activity as a lifestyle modification in studies I and II. In study I, we found that physical activity of at least 1 hour walking per day was associated with an overall breast cancer risk reduction by 23%. The risk reduction was predominantly observed for women who exercised during or after menopause and women who had lower-middle and upper-middle values of body composition. Study II examined physical activity in relation to MBD, mammographic appearances, and mode of breast cancer detection in breast cancer patients; we found no association for any of the mammographic features.We also investigated FGF/FGFR1 system and tamoxifen responses as potential targets for intervention in studies III and IV. In study III, we showed that FGFR1 expression was upregulated in almost 60% of tumor tissues versus tumor-adjacent tissues from the same patients. We further showed that FGFR1 expression was associated with less favorable tumor characteristics. We noted associations between FGF ligand expression and MBD. Study IV showed that tamoxifen inhibited the proliferation, disrupted the cell cycle progression, and inhibited the ECM adhesion capacity of healthy breast epithelial cells.In conclusion, we offer further evidence on physical activity as a breast cancer preventive measure with details on life stage and body composition. We studied mammographic appearances and mode of breast cancer detection in relation to physical activity for the first time and also proposed novel findings supporting a role for the FGF/FGFR1 system in MBD-driven breast carcinogenesis. Mechanistic insight for tamoxifen as a breast cancer preventive drug was also elucidated.