Abstract
Increased levels of pro-inflammatory markers and decreased levels of anti-inflammatory markers in the breast tissue can result in local inflammation. We aimed to investigate whether local inflammation in the breast tissue is associated with age-related lobular involution, a process inversely related to breast cancer risk. Levels of eleven pro- and anti-inflammatory markers were assessed by immunohistochemistry in normal breast tissue obtained from 164 pre- and postmenopausal breast cancer patients. Involution status of the breast (degree of lobular involution and the predominant lobule type) was microscopically assessed in normal breast tissue on hematoxylin-eosin stained mastectomy slides. Multivariate generalized linear models were used to assess the associations. In age-adjusted analyses, higher levels of pro-inflammatory markers IL-6, TNF-α, CRP, COX-2, leptin, SAA1 and IL-8; and anti-inflammatory marker IL-10, were inversely associated with the prevalence of complete lobular involution (all P≤0.04). Higher levels of the pro-inflammatory marker COX-2 were also associated with lower prevalence of predominant type 1/no type 3 lobules in the breast, an indicator of complete involution, in age-adjusted analysis (P = 0.017). Higher tissue levels of inflammatory markers, mainly the pro-inflammatory ones, are associated with less involuted breasts and may consequently be associated with an increased risk of developing breast cancer.
Highlights
Many cellular processes controlling normal breast maturation-regression have been found to be involved in cancer development
We considered eight proinflammatory markers [interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), cyclooxygenase 2 (COX-2), leptin, serum amyloid A1 (SAA1), interleukin 8 (IL-8) and signal transducers and activators of transcription 3 (STAT3)] and three anti-inflammatory markers [transforming growth factor-β (TGF-β), interleukin 10 (IL-10) and lactoferrin]
We considered two measures of the age-related lobular involution (ARLI) previously shown to be associated with breast cancer (BC) risk: the degree of lobular involution, a qualitative measure, and the predominant lobule type, a quantitative measure [10, 11, 20]
Summary
Many cellular processes controlling normal breast maturation-regression have been found to be involved in cancer development. The immune system has been linked to normal mammary gland development as well as breast carcinogenesis [1,2,3]. Continuous stimulation of the immune system by persistent tissue injury can create a state of chronic local inflammation. Chronic local inflammation provides signals that can alter the proliferation, differentiation and apoptosis of breast cells [4,5,6,7]. Mammary cells respond to these signals by maintaining cellular proliferation, accumulating reactive oxygen species and enhancing the production of more inflammatory markers. Chronic local inflammation can be expected to deregulate the physiological breast maturation-regression steps
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
