Investigating The Use Of Metformin For The Prevention Of Endometrial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$676,755.00
Summary
Endometrial (uterine) cancer affects approximately 3% of women. Obesity and oestrogen exposure are risk factors for this cancer. A novel approach to prevent endometrial cancer would be to oppose the effects of insulin and oestrogen on endometrial cell growth. This study will investigate whether metformin, commonly used to treat diabetes, blocks cellular pathways by which oestrogen and insulin stimulate endometrial cell growth, and thus evaluate the possibility that metformin might be useful in p ....Endometrial (uterine) cancer affects approximately 3% of women. Obesity and oestrogen exposure are risk factors for this cancer. A novel approach to prevent endometrial cancer would be to oppose the effects of insulin and oestrogen on endometrial cell growth. This study will investigate whether metformin, commonly used to treat diabetes, blocks cellular pathways by which oestrogen and insulin stimulate endometrial cell growth, and thus evaluate the possibility that metformin might be useful in preventing endometrial cancer.Read moreRead less
A Multi-site Study Of Tamoxifen Dose Escalation Study In Breast Cancer Patients With CYP2D6 Polymorphisms (TADE Study)
Funder
National Health and Medical Research Council
Funding Amount
$340,768.00
Summary
Tamoxifen is a selective anti-oestrogenic medication commonly used to treat breast cancer. Recent evidence suggests that tamoxifen may not be adequately activated in the body of some people because of their genetic make-up, and that this may reduce its effectiveness. In this study of 120 women, we will determine whether increasing tamoxifen dosage is a useful strategy in people with low activation levels. This could provide practical guidance for patients and clinicians managing breast cancer.
Exploring A New Way To Overcoming Endocrine Resistance In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$441,764.00
Summary
Despite significant improvements in long-term outcome with the use of endocrine therapy (such as tamoxifen and letrozole), breast cancer remains the most common cause of cancer-related death amongst Australian women. A major clinical problem limiting the effectiveness of endocrine therapy is tumour resistance, either intrinsic or acquired. Indeed, about half of patients immediately fail to respond to the treatment, while in the initially responding patients the tumours ultimately progress to res ....Despite significant improvements in long-term outcome with the use of endocrine therapy (such as tamoxifen and letrozole), breast cancer remains the most common cause of cancer-related death amongst Australian women. A major clinical problem limiting the effectiveness of endocrine therapy is tumour resistance, either intrinsic or acquired. Indeed, about half of patients immediately fail to respond to the treatment, while in the initially responding patients the tumours ultimately progress to resistance to the drug leading to the disease relapse. Therefore, it is imperative to better understand the mechanisms responsible for the resistance and to explore new strategies that overcome this clinical problem in order to prolong the overall survival of patients with breast cancer. Our recent work have shown that a recently-identified enzyme, termed sphingosine kinase, plays an important role in promoting breast cancer cell growth. We also found that cells that have a high level of the enzyme had bad outcomes in response to anti-estrogen drug, tamoxifen. Thus this project seeks to identify the role of this enzyme in contributing towards drug resistance, and test if inhibition of this enzyme could improve and-or restore the drug response in breast cancer. It will ultimately pave a new way to overcoming the drug resistance for improving the treatment and prevention of breast cancer.Read moreRead less
Wnt-5a Signalling - A Novel Therapy For Triple Negative And Tamoxifen Resistant Breast Cancer Patients
Funder
National Health and Medical Research Council
Funding Amount
$330,534.00
Summary
Breast cancer is the most common cancer in women. Commonly used drugs target the estrogen receptor (ER). However, one third of breast cancer patients lack ER, and do not respond to treatment. Cancers that lack ER also lack a gene called Wnt5a, which is linked to better prognosis. We have shown that fixing Wnt5a can restore ER allowing cells to respond to Tamoxifen. We would now test this in animals, in the hope of developing a new drug for breast cancer patients currently with limited options.
Follow-up Phase Of A Randomised Trial Of Tamoxifen Or Placebo For Breast Cancer Prevention In High Risk Women.
Funder
National Health and Medical Research Council
Funding Amount
$459,900.00
Summary
Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. Tamoxifen, a non-toxic tablet used to control the growth of breast cancer, has safely been taken by over a million women long term . This project measures tamoxifen's role in preventing breast cancer in high risk women compared to placebo, in a randomised double blind clinical trial. The trial has the potential to benefit many millions of women worldwide. The study is called IBIS1 (International ....Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. Tamoxifen, a non-toxic tablet used to control the growth of breast cancer, has safely been taken by over a million women long term . This project measures tamoxifen's role in preventing breast cancer in high risk women compared to placebo, in a randomised double blind clinical trial. The trial has the potential to benefit many millions of women worldwide. The study is called IBIS1 (International Breast cancer Intervention Study) , and is conducted in Australia by the Australian New Zealand Breast Cancer Trials Group (ANZ BCTG), and internationally by the Imperial Cancer Research Fund (ICRF) in London. On the trial women have regular, annual mammography, 6 monthly clinical checks and take a tablet each day called TAMPLAC, which is either tamoxifen or placebo. The accrual phase has been funded by the NHMRC and by November 2000 the target number of women on the trial was reached ahead of schedule - over 7000 internationally including over 2500 from Australia. Follow-up is being completed with planned data analysis within the next three years. Funding for this phase in Australia is now being sought. The ANZ BCTG and over 2500 women at increased risk of breast cancer have demonstrated a remarkable commitment to complete accrual. It is now vitally important that the essential follow-up with careful monitoring is completed to facilitate anaysis of the data at the earliest opportunity. The only other large randomised trial testing tamoxifen (NSABP P-1) ceased and unblinded in 1998, with an average follow-up of less than 4 years. This trial has had to re-commence follow-up to determine longer term tamoxifen effects. The IBIS 1 study is now the only large, blinded trial remaining in the world, and it's follow-up is of very high international importance. The completion of follow-up and the publication of results will have substantial impact worldwide.Read moreRead less
Follow-up Of A Randomised Trial Of Tamoxifen Or Placebo For Breast Cancer Prevention In High Risk Women.
Funder
National Health and Medical Research Council
Funding Amount
$893,483.00
Summary
Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. Tamoxifen, a non-toxic tablet used to control the growth of breast cancer, has safely been taken by more then a million women long term . This project measures tamoxifen's role in preventing breast cancer in high risk women compared to placebo, in a randomised double blind clinical trial. The trial has the potential to benefit many millions of women worldwide. The study, IBIS I (International Bre ....Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. Tamoxifen, a non-toxic tablet used to control the growth of breast cancer, has safely been taken by more then a million women long term . This project measures tamoxifen's role in preventing breast cancer in high risk women compared to placebo, in a randomised double blind clinical trial. The trial has the potential to benefit many millions of women worldwide. The study, IBIS I (International Breast Cancer Intervention Study), is conducted in Australia by the Australian New Zealand Breast Cancer Trials Group (ANZ BCTG), and internationally by Cancer Research UK (CRUK). On the trial women have regular, annual mammography, 6 monthly clinical checks and take a tablet each day called TAMPLAC, which is either tamoxifen or placebo. The accrual phase has been funded by the NHMRC and the target number of women on the trial was reached ahead of schedule - 7154 internationally including 2674 from Australia. By April 2006 all women will have completed the treatment phase. Funding is now being sought, in Australia, for continued follow-up and investigations of additional risk factors (breast density and types of tumors which occur-have occurred on IBIS I). The ANZ BCTG and all the women involved in IBIS I have demonstrated remarkable commitment. It is now vitally important that the essential follow-up is completed to facilitate analysis of the data, including the post-treatment phase, as well as related risk factors and types of tumors which develop. The only other large randomised trial testing tamoxifen (NSABP P-1) ceased and was unblinded in 1998, with an average follow-up of less than 4 years, the trial had to re-commence follow-up to determine longer term tamoxifen effects. The IBIS 1 study remains the only large, blinded trial in the world, and completion of it's follow-up and analysis is of very high international importance.Read moreRead less