Association between local inflammation and breast tissue age-related lobular involution among premenopausal and postmenopausal breast cancer patients

PLoS One. 2017 Aug 28;12(8):e0183579. doi: 10.1371/journal.pone.0183579. eCollection 2017.


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.

MeSH terms

  • Adult
  • Age Factors
  • Aging / pathology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / pathology*
  • Cytokines / metabolism*
  • Female
  • Humans
  • Inflammation / pathology
  • Middle Aged
  • Postmenopause
  • Premenopause


  • Cytokines

Grant support

This research was supported by grants from the Canadian Breast Cancer Research Alliance (grant #20462), the Fondation du cancer du sein du Québec and the “Banque de tissus et données of the Réseau de recherche sur le cancer” of the “Fond de recherche du Québec – Santé (FRQS)”, associated with the Canadian Tumor Repository Network (CTRNet). CD is a recipient of The Canadian Breast Cancer Foundation-Canadian Cancer Society Capacity Development award (award #703003) and the FRQS Research Scholar.