Mammographic breast density is one of the strongest risk factors for breast cancer, but molecular understanding of how breast density relates to cancer risk is less complete. Studies of proteins in blood plasma, possibly associated with mammographic density, are well-suited as these allow large-scale analyses and might shed light on the association between breast cancer and breast density.

Mammographic breast density, the white part of a mammogram, is one of the strongest risk factors for breast cancer. Dense breasts contain a large amount of fibroglandular tissue and in contrast to fat tissue; dense tissue appears white on a mammogram. Several studies have shown that women with high mammographic breast density have an increased risk to develop breast cancer. A number of variables such as age, BMI, menopausal status and the use of hormone replacement therapy are known to influence density. Still, the biological understanding of mammographic breast density is limited, as is the molecular basis for its association to breast cancer risk.

Together with a team lead by Per Hall at MEB (KI), 1329 women that had no prior history of breast cancer in the Swedish population-based KARMA study (www.karmastudy.org) were selected and plasma was analyzed with multiplexed affinity assays in order to explore proteins with association to mammographic breast density. Antibody bead arrays, targeting a total number of 357 proteins, were built with protein targets had been selected from the literature for being related to breast cancer, breast density or tissue composition.

After adjusting the data for age and BMI, linear regression analyses identified 20 proteins that were both associated to area-based mammographic breast density (p < 0.05) and concordant in two independent sample sets. Evidence for gene expression in breast tissue existed for 11 of the proteins, which functionally related tissue homeostasis, DNA repair, and cancer development and/or progression. We conducted several experiments for antibody validation in plasma by using paired antibodies and orthogonal methods such as Western blot and immuno-caputre mass spectrometry as well as high density peptide arrays for epitope mapping. As proteomics studies in relation to breast density are rare, our current finding will provide useful directions for follow-up investigations that study the molecular insights of mammographic breast density.

Read article in Breast Cancer Research

Sanna Byström