[175] Endogenous Hormone Levels and Risk of Androgen Receptor Positive Breast Cancer: Results from the Nurses' Health Study

K Cole, J Marotti, R Hu, RM Tamimi, SE Hankinson, SJ Schnitt, LC Collins. Beth Israel Deaconess Medical Center, Boston; Brigham and Women's Hospital, Boston

Background: High circulating levels of androgens as well as high estrogen levels are associated with an increased risk of estrogen receptor (ER)+ breast cancer, particularly among postmenopausal women. While many breast cancers express androgen receptor (AR), the relationship between circulating hormone levels and the risk of development of an AR+ breast cancer has not been previously investigated. An understanding of this relationship could provide new insights into the risks for AR+ breast cancer.
Design: We constructed tissue microarrays (TMAs) from paraffin blocks of breast cancers from women enrolled in the Nurses' Health Study who had provided a blood sample for assessment of circulating hormone levels. TMA sections were immunostained for ER and AR. Any nuclear staining (>1%) for ER and AR was considered positive. Plasma samples were prospectively analyzed for endogenous levels of estradiol (E2) and testosterone (T) among postmenopausal women not currently taking postmenopausal hormones at the time of blood collection. We determined the relative risks of developing ER and AR positive breast cancers in relation to circulating hormone levels among 196 cases (compared with 787 controls).
Results: Overall, 82% of the breast cancers were AR+. The Table shows the relative risk for the development of breast cancer according to ER and AR status and the circulating E2 and T levels.

Relative risk of ER+ and AR+ breast cancer according to levels of circulating hormones

Circulating hormone level	ER+ breast cancer	AR+ breast cancer
	N=151	N=151
	OR (95%CI)	OR (95%CI)
Low E2/Low T	1.0 (REF)	1.0(REF)
Low E2/High T	2.7 (1.5-4.9)	1.8 (1.0-3.2)
High E2/Low T	2.0 (1.1-3.6)	1.3 (0.7-2.3)
High E2/High T	3.2 (1.9-5.4)	2.1 (1.3-3.4)

*Adjusted for matching factors (age, fasting status, time, month of blood draw)

Either high E2, high T or both were significantly associated with ER+ breast cancers, but significantly increased risk of AR+ cancers was only seen when circulating levels of T were high, (Low E2/High T p=0.04, High E2/High T p=0.0017).
Conclusions: We found that high circulating levels of testosterone were significantly associated with development of AR+ breast cancers, irrespective of estradiol levels. A better understanding of factors involved in the development of AR+ breast cancers may help in the identification of novel risk assessment and treatment strategies.
Category: Breast

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 14, Monday Morning