Sex steroid hormones are critical in both the development and progression of breast cancer. The key role of estrogen signaling is well recognized, and drugs that target this pathway are a cornerstone of breast cancer treatment and chemoprevention. An important role for androgens in breast cancer biology also has long been hypothesized but remains to be elucidated. The androgen receptor (AR) is expressed in a significant number of normal breast epithelial cells and in 60-70% of breast tumors. However, remarkably little is known about the role of androgens in normal or malignant breast tissue. Circulating androgens have been shown to be positively associated with breast cancer risk, and AR expression with breast cancer prognosis. The impact of androgen signaling on breast cancer survival may vary by estrogen receptor (ER) status of the tumor. We hypothesize that androgen receptor expression and signaling in normal breast tissue is associated higher risk of developing breast cancer and that androgen receptor expression leads to better survival in women with ER+ breast tumors and worse survival in women with ER- breast tumors. This project will test these hypotheses by 1) evaluating the role of AR expression in breast cancer risk in the Nurses' Health Study Benign Breast Disease Nested Case-Control Study, 2) evaluating the role of AR signaling in breast cancer risk in the Nurses' Health Study Benign Breast Disease Nested Case-Control Study, and 3) evaluating the role of AR expression in breast cancer prognosis in the Nurses' Health Study and Nurses' Health Study II. Elucidating the role of androgen receptor signaling in breast cancer carcinogenesis and prognosis is vital as this information will improve our understanding of etiologic mechanisms and could introduce new opportunities for chemoprevention and therapeutics.
Breast cancer is the leading cause of cancer incidence and mortality globally among women, accounting for an estimated 1.68 million new cases and 521,000 deaths in 2012. Steroid receptor signaling is critical for breast cancer development and progression, with the role of estrogens well elucidated, but the role of androgens unclear. This project will evaluate the role of androgen receptor expression and signaling on breast cancer risk and prognosis.
|Kensler, Kevin H; Beca, Francisco; Baker, Gabrielle M et al. (2018) Androgen receptor expression in normal breast tissue and subsequent breast cancer risk. NPJ Breast Cancer 4:33|
|Kensler, Kevin H; Sankar, Venkat N; Wang, Jun et al. (2018) PAM50 Molecular Intrinsic Subtypes in the Nurses' Health Study Cohorts. Cancer Epidemiol Biomarkers Prev :|
|Beca, Francisco; Kensler, Kevin; Glass, Benjamin et al. (2017) EZH2 protein expression in normal breast epithelium and risk of breast cancer: results from the Nurses' Health Studies. Breast Cancer Res 19:21|