Expression of interleukin-6 and tumor necrosis factor α and histopathologic findings in painful and nonpainful breast tissue

Mastalgia is a common condition that is thought to be hormonally related, but the mechanisms of pain causation are unknown. Inflammatory cytokines are implicated in pain modulation, but have not been studied with regard to mastalgia. We compared the relationship of mastalgia to the expression of the cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α and the degree of tissue infiltration with inflammatory cells in breast tissue from 29 premenopausal women with breast pain and 29 age-matched pain-free controls. Paraffin sections from breast biopsy samples were scored for the presence of inflammatory infiltrate and were evaluated for the expression of IL-6, IL-1β, and TNF-α using standard immunohistochemical procedures. TNF-α and IL-6 expression displayed a trend toward slightly lower values in patients with pain (median TNF-α score, 3 versus 5; median IL-6 score, 3 versus 4). In the luteal phase, patients with mastalgia showed a trend toward lower expression of IL-6 (p = 0.4) in comparison to those without pain. A similar trend was also seen with TNF-α expression (p = 0.4). IL-1β expression was extremely scant in the first 30 samples and was not investigated further. The degree of inflammatory infiltrate in the tissue was unrelated to the presence of breast pain. These data suggest that the three cytokines tested in this study do not play a significant role in the causation of mastalgia and lend weight to the previous finding that there are no identifiable histologic correlates of this troubling condition. Further investigation of the role of cytokines in breast pain is warranted, especially in view of the possible association between mastalgia and breast cancer risk.