The G protein-coupled receptor GPR30 inhibits proliferation of estrogen receptor-positive breast cancer cells.

The G protein-coupled receptor GPR30 binds 17beta-estradiol (E(2)) yet differs from classic estrogen receptors (ERalpha and ERbeta). GPR30 can mediate E(2)-induced nongenomic signaling, but its role in ERalpha-positive breast cancer remains unclear. Gene expression microarray data from five cohorts comprising 1,250 breast carcinomas showed an association between increased GPR30 expression and ERalpha-positive status.

Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen.

Aromatase inhibitors (AI) are being evaluated as long-term adjuvant therapies and chemopreventives in breast cancer. However, there are concerns about bone mineral density loss in an estrogen-free environment. Unlike nonsteroidal AIs, the steroidal AI exemestane may exert beneficial effects on bone through its primary metabolite 17-hydroexemestane.

Exploiting the apoptotic actions of oestrogen to reverse antihormonal drug resistance in oestrogen receptor positive breast cancer patients.

The ubiquitous application of selective oestrogen receptor modulators (SERMs) and aromatase inhibitors for the treatment and prevention of breast cancer has created a significant advance in patient care. However, the consequence of prolonged treatment with antihormonal therapy is the development of drug resistance. Nevertheless, the systematic description of models of drug resistance to SERMs and aromatase inhibitors has resulted in the discovery of a vulnerability in tumour homeostasis that can be exploited to improve patient care.

Emerging principles for the development of resistance to antihormonal therapy: implications for the clinical utility of fulvestrant.

We seek to evaluate the clinical consequences of resistance to antihormonal therapy by studying analogous animal xenograft models. Two approaches were taken: (1) MCF-7 tumors were serially transplanted into selective estrogen receptor modulator (SERM)-treated immunocompromised mice to mimic 5 years of SERM treatment. The studies in vivo were designed to replicate the development of acquired resistance to SERMs over years of clinical exposure.