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Association between expression of inflammatory markers in normal breast tissue and mammographic density among premenopausal and postmenopausal women

Hanna, Mirette MD, PhD1,2,3; Dumas, Isabelle MSc1; Orain, Michèle MLT1; Jacob, Simon MD1,2,3,4,5; Têtu, Bernard MD1,2,3,4,5; Sanschagrin, François PhD1,3,5; Bureau, Alexandre PhD2,6; Poirier, Brigitte MD1,2,3,5; Diorio, Caroline PhD1,2,3,5

doi: 10.1097/GME.0000000000000794
Original Articles

Objective: Inflammatory markers may be associated with breast cancer risk. We assessed the association between expression levels of proinflammatory (interleukin 6, tumor necrosis factor-α, C-reactive protein, cyclooxygenase 2, leptin, serum amyloid A1, interleukin 8, and signal transducer and activator of transcription 3) and anti-inflammatory markers (transforming growth factor-β, interleukin 10, and lactoferrin) in normal breast tissue with mammographic density, a strong breast cancer risk indicator, among 163 breast cancer patients.

Methods: The expression of inflammatory markers was visually evaluated on immunohistochemistry stained slides. The percent mammographic density (PMD) was estimated by a computer-assisted method in the contralateral cancer-free breast. We used generalized linear models to estimate means of PMD by median expression levels of the inflammatory markers while adjusting for age and waist circumference.

Results: Higher expression levels (above median) of the proinflammatory marker interleukin 6 were associated with higher PMD among all women (24.1% vs 18.5%, P = 0.007). Similarly, higher expression levels (above median) of the proinflammatory markers (interleukin 6, tumor necrosis factor-α, C-reactive protein, and interleukin 8) were associated with higher PMD among premenopausal women (absolute difference in the PMD of 8.8% [P = 0.006], 7.7% [P = 0.022], 6.7% [P = 0.037], and 16.5% [P = 0.032], respectively). Higher expression levels (above median) of the anti-inflammatory marker transforming growth factor-β were associated with lower PMD among all (18.8% vs 24.3%, P = 0.005) and postmenopausal women (14.5% vs 20.7%, P = 0.013).

Conclusions: Our results provide support for the hypothesized role of inflammatory markers in breast carcinogenesis through their effects on mammographic density. Inflammatory markers could be targeted in future breast cancer prevention interventions.

Supplemental Digital Content is available in the text

1Oncology Axis, Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec, Université Laval, Quebec, Canada

2Faculté de médecine, Université Laval, Quebec, Canada

3Centre des Maladies du Sein Deschênes-Fabia, Hôpital du Saint-Sacrement, Quebec, Canada

4Pathology and Molecular Biology Services, Hôpital Saint-Sacrement, CHU de Québec, Université Laval, Quebec, Canada

5Centre de recherche sur le cancer de l’Université Laval, Quebec, Canada

6Centre de Recherche de l’Institut Universitaire en Santé Mentale de Québec, Université Laval, Quebec, Canada.

Address correspondence to: Caroline Diorio, PhD, Oncology Axis, Centre de Recherche du CHU de Québec, Université Laval, 1050 chemin Sainte-Foy, Quebec City, QC G1S 4L8, Canada. E-mail: Caroline.Diorio@crchudequebec.ulaval.ca

Received 9 July, 2016

Revised 28 September, 2016

Accepted 28 September, 2016

Conception and design—M.H., S.J., B.T., F.S., A.B., and C.D.; development of methodology—M.H., S.J., B.T., and C.D.; acquisition of data—I.D. and C.D.; analysis and interpretation of data—M.H., I.D., and C.D.; writing of the manuscript—M.H.; revision of the manuscript—M.H., M.O., S.J., B.T., F.S., A.B., B.P., and C.D.; administrative, technical, or material support—M.H., I.D., M.O., S.J., B.T., F.S., A.B., B.P., and C.D.; and study supervision—C.D.

Funding/support: This research was supported by a grant from the Canadian Breast Cancer Research Alliance (grant #20462) 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). C.D. is a recipient of The Canadian Breast Cancer Foundation-Canadian Cancer Society Capacity Development award (award #703003) and the FRQS Research Scholar.

Financial disclosure/conflicts of interest: None reported.

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© 2017 by The North American Menopause Society.