FGF/FGFR1 system in paired breast tumor-adjacent and tumor tissues, associations with mammographic breast density and tumor characteristics.

Introduction: Mammographic breast density (MBD) is an established breast cancer risk factor, yet the underlying molecular mechanisms remain to be deciphered. Fibroblast growth factor receptor 1 (FGFR1) amplification is associated with breast cancer development and aberrant FGF signaling found in the biological processes related to both high mammographic density and breast cancer microenvironment. The aim of this study was to investigate the FGF/FGFR1 expression in-between paired tumor-adjacent and tumor tissues from the same patient, and its associations with MBD and tumor characteristics. Methods: FGFR1 expression in paired tissues from 426 breast cancer patients participating in the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) cohort study was analyzed by immunohistochemistry. FGF ligand expression was obtained from RNA-sequencing data for 327 of the included patients. Results: FGFR1 levels were differently expressed in tumor-adjacent and tumor tissues, with increased FGFR1 levels detected in 58% of the tumors. High FGFR1 expression in tumor tissues was associated with less favorable tumor characteristics; high histological grade (OR=1.86, 95% CI 1.00-3.44), high Ki67 proliferative index (OR=2.18, 95% CI 1.18-4.02) as well as tumors of Luminal B-like subtype (OR=2.56, 95%CI 1.29-5.06). While no clear association between FGFR1 expression and MBD was found, FGF ligand (FGF1, FGF11, FGF18) expression was positively correlated with MBD. Discussion: Taken together, these findings support a role of the FGF/FGFR1 system in early breast cancer which warrants further investigation in the MBD-breast cancer context.

Physical Activity and Long-Term Risk of Breast Cancer, Associations with Time in Life and Body Composition in the Prospective Malmö Diet and Cancer Study.

Being physically active as part of everyday life reduces breast cancer risk. Less is known whether the benefits of an active lifestyle differ depending on the timing of physical activity in life or anthropometric characteristics. The aim of this study was to bring further insights to the association of physical activity in relation to menopausal status and body composition with breast cancer risk by making use of a prospective Swedish cohort (Malmö Diet and Cancer Study) with long-term follow-up. Physical activity information of 15,983 participants for the past 12 months prior to study entry was assessed according to metabolic equivalent task (MET)-hours/week to integrate duration and intensity of reported activities. During 23.2 years median follow-up, 1302 invasive breast cancers occurred. Women reporting a high physical activity at study baseline, corresponding to >1 h daily walking/week (≥28.5 MET-h/week), had a 23% lower long-term breast cancer risk (HRadj = 0.77, 95% CI 0.66−0.90) than those reporting low physical activity, being most pronounced among perimenopausal and postmenopausal women, and women with waist circumference, body fat percentage, or BMI in the upper-normal and overweight range. For premenopausal women or women having obesity or the largest body composition, high physical activity alone did not modify the breast cancer risk, suggesting additional preventive measures indicated in these groups to reduce the long-term risk of breast cancer.