A Randomised Phase III Trial Of Anastrozole For Breast Cancer Prevention In Postmenopausal Women At High Risk.
Funder
National Health and Medical Research Council
Funding Amount
$1,593,125.00
Summary
Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. This project (IBIS 2) is designed to continue the work started by the IBIS 1 prevention trial in determining whether a chemopreventive strategy towards breast cancer is beneficial. IBIS 1 investigated the use of tamoxifen as a preventative agent for women with moderate to increased risk of developing breast cancer and was found to prevent 48% of oestrogen receptor positive breast cancers. IBIS 2 ....Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. This project (IBIS 2) is designed to continue the work started by the IBIS 1 prevention trial in determining whether a chemopreventive strategy towards breast cancer is beneficial. IBIS 1 investigated the use of tamoxifen as a preventative agent for women with moderate to increased risk of developing breast cancer and was found to prevent 48% of oestrogen receptor positive breast cancers. IBIS 2 investigates anastrozole (Arimidex) as a preventative agent for women with moderate to increased risk of developing breast cancer. It is a multi-centre, randomised, double blind control trial which has the potential to benefit many millions of women worldwide. Anastrozole is an aromatase inhibitor (AI). AIs are a class of endocrine drug which have been shown to be at least as effective as tamoxifen but without the serious side effects seen with tamoxifen. Anastrozole has been shown to be 60% better than tamoxifen in preventing a second breast cancer in women already diagnosed with breast cancer. Women who participate in this study will be postmenopausal with a relative risk of at least two-fold of developing breast cancer. They will be randomised to receive either anastrozole or placebo as a daily tablet, and neither the woman nor her treating clinician will know which treatment has been allocated (double blind study). To investigate whether anastrozole effects bone density, a baseline bone density scan will be measured prior to study entry. This sub-study will investigate bone density in greater detail and the potential role of bone preserving treatment (bisphosphonate). The primary endpoint for the IBIS 2 study is the development of histologically confirmed breast cancer, invasive or non-invasive.Read moreRead less
IBIS II: A Randomised Phase III Trial Of Anastrozole For Breast Cancer Prevention In Postmenopausal Women At High Risk.
Funder
National Health and Medical Research Council
Funding Amount
$1,732,559.00
Summary
The IBIS II trial builds on the successful IBIS 1 breast cancer (BC) prevention trial in determining whether a chemopreventive strategy towards BC is beneficial. Women who are postmenopausal with an increased risk of BC are randomised to receive either anastrozole (an aromatase inhibitor) or placebo as a daily tablet. Neither the woman nor her clinician know which treatment has been allocated (double blind study). IBIS 2 has the potential to benefit many higher risk women worldwide.
Sex Steroids Modulate The Neuronal Control Of Bone Formation
Funder
National Health and Medical Research Council
Funding Amount
$620,647.00
Summary
It is well recognised that changes in sex hormones are pivotal to the development of osteoporosis in both men and women. Our group has been instrumental in identifying a novel and powerful system regualting bone mass and strength by neural activity. Recent findings indicate critical interactions between these two pathways in the control of bone formation. Greater understanding of these interactions could lead to therapies capable of controlling this extremely common disease.
Prevention Of Late Breast Cancer (BC) Events In Postmenopausal Women With Endocrine Responsive BC.
Funder
National Health and Medical Research Council
Funding Amount
$4,687,599.00
Summary
This proposal is from Australia's national breast cancer (BC) trials group, the ANZ BCTG, for a new phase III, multi-centre clinical trial evaluating whether much later endocrine therapy with an aromatase inhibitor can prevent BC recurrence in postmenopausal women who have: had hormone sensitive BC at least 6 years ago; were treated by Tamoxifen more than 1 year ago; and, are currently disease free. Subjects will randomly receive letrozole or placebo as a daily tablet for five years.
Osteoporosis is a major health burden resulting from bone fractures in older men and women due to progressive loss of bone and weakening of the skeleton. No current treatment effectively reverses this bone loss. Using genetic models in mice, we have identified a pathway, involving the nerve signal molecule NPY, that is capable of inducing large (200 - 300%) increases in bone very rapidly (within a few weeks), in the skeleton of adult mice. This proposal is aimed at characterising this new pathwa ....Osteoporosis is a major health burden resulting from bone fractures in older men and women due to progressive loss of bone and weakening of the skeleton. No current treatment effectively reverses this bone loss. Using genetic models in mice, we have identified a pathway, involving the nerve signal molecule NPY, that is capable of inducing large (200 - 300%) increases in bone very rapidly (within a few weeks), in the skeleton of adult mice. This proposal is aimed at characterising this new pathway to assess its potential to provide new treatments for human osteoporosis. This research is important because of the size, rapidity and inducibility of the effect. Moreover, since it originates in the brain, it represents a quite novel mechanism by which the skeleton is potentially maintained and repaired. The experiments contained in the initial sections of the proposal are designed to assess not only the ability of the NPY-pathway to protect against bone loss but also to examine the possibility of repair to a fragile skeleton. The bone loss models chosen for study represent postmenopausal and age-related osteoporosis, two prevalent and increasingly common conditions in the aging world population. The latter section of the proposal seeks to clarify the mechanism by which the increase in bone formation occurs within the bone. Understanding the working of this pathway will be vital in developing future treatment regimens. This proposal investigates a novel, powerful and rapid pathway for repairing weakened skeletons. The knowledge resulting from this proposal has the potential to provide an important contribution to skeletal health and thus aged health worldwide.Read moreRead less
Targeting The Gonadotropin-releasing Signal Transduction Cascade Novel Approaches To Regulating Reproduction And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$438,625.00
Summary
We know that nutrition and reproduction are closely linked e.g. undernutrition leads to infertility, menopause to weight gain, but we do not know precisely the mechanisms whereby these events occur. The brain hormone gonadotropin-releasing hormone (GnRH), which stimulates the reproductive pathways and a recently discovered family of hormones (orexins) which stimulate feeding both act through the same type of recognition site i.e. G-protein coupled receptors (GPCRs) which are distributed in close ....We know that nutrition and reproduction are closely linked e.g. undernutrition leads to infertility, menopause to weight gain, but we do not know precisely the mechanisms whereby these events occur. The brain hormone gonadotropin-releasing hormone (GnRH), which stimulates the reproductive pathways and a recently discovered family of hormones (orexins) which stimulate feeding both act through the same type of recognition site i.e. G-protein coupled receptors (GPCRs) which are distributed in close proximity within the brain. Identifying how these two pathways interact has enormous potential for the treatment of disorders of weight and-or reproduction since the GPCR structure and the route by which it signals lends itself to therapeutic intervention.Read moreRead less