Stephen Birrell

University of Adelaide · Discipline of Medicine

1020 Background: The AR is expressed in up to 90% of ER+ breast cancer where it acts as a tumor suppressor. Historically, therapy with synthetic androgens had efficacy, but virilizing side effects and toxicity limited their use. Enobosarm is a selective AR activating agent that does not cause masculinization and has positive attributes such as prom...

Introduction: Hormonal agents remain the most effective therapies for estrogen receptor positive (ER+) HER2- breast cancer. The androgen receptor (AR) is the most highly expressed steroid receptor found in up to 95% of ER+ breast cancer patients. Androgen agonists have antiproliferative activity in ER+ breast cancer and have been used in treatment,...

The role of the androgen receptor (AR) in estrogen receptor (ER)-α-positive breast cancer is controversial, constraining implementation of AR-directed therapies. Using a diverse, clinically relevant panel of cell-line and patient-derived models, we demonstrate that AR activation, not suppression, exerts potent antitumor activity in multiple disease...

PurposeTo evaluate the efficacy of testosterone supplementation for improving aromatase inhibitor musculoskeletal symptoms (AIMSS).Methods Postmenopausal women experiencing moderate-to-severe arthralgias while taking adjuvant aromatase inhibitors for breast cancer were enrolled in this trial. Initially, patients were randomly allocated to receive e...

Antagonistic sex hormone activity occurs in mammary gland development, whereby estrogen stimulates and androgen inhibits post-pubertal growth, but the mechanistic basis of this is largely unknown. Whether sex hormone antagonism occurs in the context of breast cancer is also unclear. The estrogen receptor alpha (ER) unequivocally drives the majority...

There is strong interest in targeting the androgen receptor (AR) in estrogen receptor (ER) positive breast cancer, but widespread confusion exits as to what therapeutic strategy - agonism or antagonism - is appropriate. Current understanding of AR predominantly stems from the field of prostate cancer, where AR is the key oncogenic driver and therap...

p>The Androgen receptor (AR) is expressed in up to 90% of primary ER-positive (ER+) breast cancer and high expression of AR is an independent prognostic factor associated with good outcome. Its role in the context of ER+ breast cancer is very controversial and has constrained clinical implementation of new drugs that influence AR activity for treat...

Background: Apolipoprotein D (ApoD) is an androgen and estrogen regulated protein and a major constituent of breast cysts. Although reported to be a marker of breast cancer, the prognostic importance of ApoD in invasive breast cancer is unclear. Aim: To investigate the relationship between ApoD protein expression, together with estrogen receptor...

Table S1. Clinical and pathological characteristics of tumors used in this study. Table S2. Summary of antibodies and conditions for immunohistochemistry. Table S3. Primer sequences/Taqman Probe Assay IDs. Table S4. Number of ER binding peaks identified by Mac Peak caller. Fig. S1. Representative images of EdU staining in prostate cancer PDEs....

Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient‐derived material; however, issues related to low take rate, long duration of establishment...

Background: Dehydroepiandrosterone (DHEA) is helpful for treating vaginal symptoms. This secondary analysis evaluated the impact of vaginal DHEA on hormone concentrations, bone turnover, and vaginal cytology in women with a cancer history. Methods: Postmenopausal women, diagnosed with breast or gynecologic cancer, were eligible if they reported...

Purpose: Consensus is lacking regarding the androgen receptor (AR) as a prognostic marker in breast cancer. The objectives of this study were to comprehensively review the literature on AR prognostication and determine optimal criteria for AR as an independent predictor of breast cancer survival. Experimental design: AR positivity was assessed b...

The importance of androgen receptor (AR) signaling is increasingly being recognized in breast cancer, which has elicited clinical trials aimed at assessing the efficacy of androgen deprivation therapy (ADT) for metastatic disease. In prostate cancer, resistance to ADT is frequently associated with the emergence of androgen-independent splice varian...

Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-α (ERα) function and breast cancer prognosis. Here we show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding...

We would like to acknowledge the support of the University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. Research reported in this manuscript was supported by the National Cancer Institute of the National Institutes of Health under award number 5P30CA142543 (to UT Southwestern) and Department of Defense grants W81XWH-12-1-0288-03...

Medroxyprogesterone acetate (MPA) has widely been used in hormone replacement therapy (HRT), and is associated with an increased risk of breast cancer, possibly due to disruption of androgen receptor (AR) signaling. In contrast, the synthetic HRT Tibolone does not increase breast density, and is rapidly metabolized to estrogenic 3α-OH-tibolone and...

Objective: Medroxyprogesterone acetate (MPA), a component of combined estrogen-progestin therapy (EPT), has been associated with increased breast cancer risk in EPT users. MPA can bind to the androgen receptor (AR), and AR signaling inhibits cell growth in breast tissues. Therefore, the aim of this study was to investigate the potential of MPA to...

Background: The authors present a technique for mastectomy with greater versatility for reconstruction. Methods: The areola is marked and a vertical line is dropped medial to the breast axis, down towards the inframammary fold and laterally to the anterior axillary line. In large ptotic breasts, the markings are modified to reduce the skin envel...

The cellular response to circulating sex steroids is more than the sum of individual hormone actions, instead representing an interplay between activities of the evolutionarily related steroid hormone receptors. An example of this interaction is in breast cancer, where the risk of dying from estrogen receptor-α (ERα)-positive disease decreases appr...

Recent evidence indicates that the estrogen receptor-α-negative, androgen receptor (AR)-positive molecular apocrine subtype of breast cancer is driven by AR signaling. The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype; its proliferation is stimulated by androgens such as 5α-dihydrotestosterone (DHT) but inhibited by t...

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Consistent with several observational studies examining combined hormone replacement therapy (cHRT: conjugated equine estrogen in conjunction with the synthetic progestin medroxyprogesterone acetate, MPA) in postmenopausal women, a re-analysis of the placebo-controlled r...

Combined hormone replacement therapy (cHRT) comprised of equine estrogens and the synthetic progestin medroxyprogesterone acetate (MPA) increases breast cancer risk in post-menopausal women [1], via as yet undetermined mechanisms. In addition to the progesterone receptor (PR), MPA binds with high affinity to the androgen receptor (AR), and therefor...

Background: Aromatase inhibitors (AI) are currently used as first line adjuvant therapy for postmenopausal women with estrogen receptor (ER) positive breast cancer. Side effects of AI therapy, such as arthralgia, can cause significant patient discomfort leading to compliance issues. This may be exacerbated by low tissue testosterone (T), which is n...

s: Thirty-Second Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 10‐13, 2009; San Antonio, TX Background: Approximately 50% of women taking 3rd generation aromatase inhibitors (AI) for adjuvant breast cancer therapy develop arthralgia, tenosynovitis or arthritis. In many women, the morbidity is significant and affects therapy compliance...

Breast cancer and prostate cancer are the two most common invasive cancers in women and men, respectively. Although these cancers arise in organs that are different in terms of anatomy and physiological function both organs require gonadal steroids for their development, and tumours that arise from them are typically hormone-dependent and have rema...

There is emerging evidence that the balance between estrogen receptor-alpha (ER(alpha)) and androgen receptor (AR) signaling is a critical determinant of growth in the normal and malignant breast. In this study, we assessed AR status in a cohort of 215 invasive ductal breast carcinomas. AR and (ER(alpha)) were coexpressed in the majority (80-90%) o...

Androgen signaling, mediated by the androgen receptor (AR), is a critical factor influencing growth of normal and malignant breast cells. Given the increasing use of exogenous androgens in women, a better understanding of androgen action in the breast is essential. This study compared the effects of 5alpha-dihydrotestosterone (DHT) and a synthetic...

There is now considerable evidence that using a combination of synthetic progestins and estrogens in hormone replacement therapy (HRT) increases the risk of breast cancer compared with estrogen alone. Furthermore, the World Health Organization has recently cited combination contraceptives, which contain synthetic progestins, as potentially carcinog...

Rationale Treatment guidelines recommend a more conservative surgical approach than mastectomy for early stage breast cancer and a stronger emphasis on adjuvant therapy. Registry data at South Australian teaching hospitals have been used to monitor survivals and treatment in relation to these guidelines. Aims and objectives To use registry data to:...

Previously, we reported that androgen receptor (AR), but not estrogen receptor (ER) or progesterone receptor (PR), is predictive of response to the synthetic progestin, medroxyprogesterone acetate (MPA), in a cohort of 83 patients with metastatic breast cancer. To further investigate the role of AR in determining response to MPA in this cohort, we...

Survivals from breast cancer varied by location of lesion (P<0.001), with 10-year survivals of 61% applying for central (n=772), 73% for medial (n=350), and 72% for lateral (n=966) lesions. Univariate analyses of determinants of central locations indicated that the following were predictive: a more advanced TNM stage (P<0.001); a larger tumour diam...

The Hormones and Cancer 2000 Conference was held from 3–7 November 2000 in Port Douglas, Australia.

Medroxyprogesterone acetate (MPA), which is frequently used as second line hormonal therapy for the treatment of metastatic breast cancer, binds with high affinity to the progesterone receptor (PR). However, the androgenic side-effects of MPA suggest that it may also activate androgen receptor (AR) regulated pathways. Treatment of the human breast...

Androgens regulate breast cancer cell proliferation via androgen receptor (AR)-mediated mechanisms. To investigate further the androgen-responsiveness of human breast tumours, we examined the immunohistochemical expression of the AR and two androgen-regulated proteins, prostate-specific antigen (PSA) and gross cystic disease fluid protein-15 (GCDFP...

Although the androgen receptor (AR)3 is often co-expressed with the estrogen receptor (ER) and progesterone receptor (PR) in human breast tumors, its role in breast cancer is poorly understood. Specific growth stimulatory and inhibitory actions of androgens have been described in human breast cancer cell lines. The mechanisms by which androgens exe...

Little is known regarding the activity and function of the androgen receptor (AR) in human breast cancer. In the present study AR was evaluated in untreated primary breast cancers using antisera to the amino- and carboxy-termini of the receptor and quantitated using colour video image analysis. A strong correlation between tissue concentration and...

EDITORIAL COMMENT: We accepted this case for publication because it shows that acute colonic pseudoobstruction can occur during pregnancy and may be successfully managed by colonoscopy as in this patient. For readers' interest we direct them to 2 previous case reports on Ogilvie syndrome which occurred post-Caesarean section and which were complica...

To determine the predictive value of androgen receptor (AR) levels in primary tumors of women who undergo medroxyprogesterone acetate (MPA) therapy for advanced breast cancer after relapse on tamoxifen adjuvant therapy. Between 1984 and 1987 at Flinders Medical Centre, South Australia, 136 postmenopausal women received adjuvant tamoxifen therapy fo...

PURPOSETo determine the predictive value of androgen receptor (AR) levels in primary tumors of women who undergo medroxyprogesterone acetate (MPA) therapy for advanced breast cancer after relapse on tamoxifen adjuvant therapy.METHODS Between 1984 and 1987 at Flinders Medical Centre, South Australia, 136 postmenopausal women received adjuvant tamoxi...

Although the majority of primary human breast cancers express the androgen receptor (AR), the role of androgens in breast cancer growth and progression is poorly understood. We have investigated the effects of the naturally occurring androgen, dihydrotestosterone (DHT), and a synthetic non-metabolizable androgen, mibolerone, on the proliferation of...

Over a 10 year period, four patients with paraduodenal hernia were encountered. Two had small hernias that were incidental findings at the time of surgery for an unrelated abdominal condition; these were managed by suture closure of the neck of the sac. The other two patients presented with intestinal obstruction and are discussed here with a revie...

The role of androgens and the androgen receptor (AR) in the development and progression of breast cancer is poorly understood. To further define a potential model for androgen action in breast cancer, MDA-MB-453 cells, which express AR in the absence of oestrogen receptors and progesterone receptors, were further characterised in terms of AR expres...