Abstract LB-179: Expression of estrogen receptor, progesterone receptor, and ki67 in normal breast tissue and subsequent risk of breast cancer
Authors: Oh Hannah , Eliassen A Heather , Wang Molin , Smith-Warner Stephanie A. , Beck Andrew H. , Schnitt Stuart J. , Collins Laura C. , Connolly James L. , Montaser-Kouhsari Laleh , Tamimi Rulla M. 
Published: August 2015

Background: Biological activity, including potential carcinogenic effects, of estrogen and progesterone in breast tissue is primarily mediated by their receptors in the tissue. Ki67 is a marker of cell cycle activation. We examined the associations of estrogen receptor (ER), progesterone receptor (PR), and Ki67 expression in normal breast tissue from benign biopsies with subsequent breast cancer risk.

Methods: We conducted an analysis among 385 women (90 cases, 295 controls) with benign breast disease (BBD) in a nested case-control study within the Nurses’ Health Study (NHS) and the NHSII. Tissue microarrays (TMA) were constructed using cores obtained from benign biopsies containing normal terminal duct lobular units (TDLU). Immunohistochemical staining for ER, PR, and Ki67 was performed on sections cut from the TMAs. Staining results were interpreted by computational image analysis which scored the percentage of positively stained cells for each marker. Unconditional logistic regression models, adjusting for matching factors and benign lesion subtype, were used to estimate odds ratios (OR) for developing subsequent breast cancer by tertiles of marker expression.

Results: ER and Ki67 expression (highest vs. lowest tertiles) in normal breast TDLUs was not significantly associated with subsequent breast cancer risk (≥14.7 vs. &lt;7.3% ER-positive cells: OR = 0.55, 95% CI = 0.21-1.44, p-trend = 0.85; ≥6.2 vs. &lt; 2.4% Ki67-positive cells: OR = 1.75, 95% CI = 0.87-3.50, p-trend = 0.15). PR expression was suggestively positively associated with breast cancer risk (≥9 vs. &lt;4%: OR = 2.08, 95% CI = 1.00-4.31, p-trend = 0.06); the positive association was significant among women who were premenopausal at BBD biopsy (OR = 3.55, 95% CI = 1.28-9.87, p-trend = 0.03).

Conclusion: PR expression in normal breast tissue was significantly positively associated with subsequent breast cancer risk in premenopausal women. Although we did not observe significant results with ER and Ki67, we cannot exclude associations given the limited power in this study. These findings may contribute to understanding of breast cancer biology and may suggest new targets for breast cancer risk assessment and prevention. However, further studies are required to confirm these results.

Citation Format: Hannah Oh, A Heather Eliassen, Molin Wang, Stephanie A. Smith-Warner, Andrew H. Beck, Stuart J. Schnitt, Laura C. Collins, James L. Connolly, Laleh Montaser-Kouhsari, Rulla M. Tamimi. Expression of estrogen receptor, progesterone receptor, and ki67 in normal breast tissue and subsequent risk of breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-179. doi:10.1158/1538-7445.AM2015-LB-179