Flaxseed and Tamoxifen Alters the Expression of Extracellular microRNA in Normal Human Breast Tissue in Vivo

Exposure to sex steroids is key in the development of breast cancer with to date limited knowledge of the mechanisms involved. Studies of sex steroid dependent alterations in normal breast tissue are needed for the development of novel preventive strategies. Diet modifications may be among the means for breast cancer prevention as women with Eastern diet habits including ingestions of phytoestrogens exhibit a lower risk of developing breast cancer. One of the riches sources of phytoestrogens in Western diet is flaxseed. We have previously shown that hormone exposure alter extracellular levels several proteins and extracellular microRNAs in vivo in normal human breast tissue. Here, we sampled extracellular microRNAs locally in situ using microdialysis in normal human breast tissue and subcutaneous abdominal fat. Different cohorts of women were included; premenopausal women investigated during the menstrual cycle before and after the addition of 25 g of ground flaxseed every day for four weeks and postmenopausal women investigated in their normal healthy breast and subcutaneous fat before and after six weeks of tamoxifen therapy. Samples were screened using TaqMan array cards with subsequently absolute quantification. Over 100 miRNA were expressed in microdialysates from breast tissue. Absolute quantifications revealed that several extracellular miRNAs were significantly altered in normal human breast tissue after flaxseed addition to the diet or tamoxifen therapy. None of these changes were found in plasma or microdialysates from subcutaneous fat. Our data revealed breast tissue specific changes of extracellular miRNAs after diet interventions and tamoxifen therapy that would be otherwise unraveled using blood samples alone. Dietary modifications may be used to prevent breast cancer, but possible mechanisms involved in the effects of flaxseed requires further studies before any general recommendations can be given.