Mechanism Of Breast Cancer Metastasis: Tumour Cell Remodelling Of The Extracellular Matrix
Funder
National Health and Medical Research Council
Funding Amount
$377,331.00
Summary
The main complication in breast cancers leading to death is metastatic relapse. This research aims to understand the role for a protease that promotes spread of breast cancer to the lymph nodes and lungs. The outcomes will identify a novel process that leads to lymph node metastasis and offer a new target for therapies that prevent relapse and tests to identify breast cancer patients at risk of relapse.
The Role Of Subcapsular Sinus Macrophages In Lymph Node Metastases
Funder
National Health and Medical Research Council
Funding Amount
$451,010.00
Summary
This project tackles the problem of lymph node metastases using complementary studies in mouse models and human patients with melanoma. It takes the novel approach of examining the local geographical factors in the lymph node and focusses on a rare cell called the subcapsular sinus macrophage that may be a critical determinant of the clinical outcome. This will result in innovative strategies for primary prevention of not only melanoma but other cancer cell metastases.
The Sentinel Lymph Node Territories Of The Whole Body And Their Clinical Implications: A Human Cadaver Study
Funder
National Health and Medical Research Council
Funding Amount
$602,984.00
Summary
Lymph gland screening with isotopes (Lymphoscintigraphy) has revealed unexpected pathways of cancer spread. This study, using an X-ray injection technique in human cadavers, is re-evaluating the outdated Melways Roadmap of lymph vessel pathways. The aims are to give accurate predictions of cancer spread, explain unusual clinical manifestations and to provide a new method of treating lymphoedema, the incapacitating swelling of limbs that may complicate lymph gland surgery or radiotherapy.
Randomised Trials Of Adjuvant Cytotoxic & Endocrine Therapy For Early N+ And N- Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$510,509.00
Summary
This application covers 4 adjuvant early breast cancer trials currently part of the Australian New Zealand Breast Cancer Trials Group's national research programme. These trials are international collaborations involving the International Breast Cancer Study Group (IBCSG). Two of the studies concern pre, peri and post-menopausal women with early breast cancer and no involved lymph glands (IBCSG 8 and 9), and two concern pre, peri and post-menopausal women with early breast cancer and involved ly ....This application covers 4 adjuvant early breast cancer trials currently part of the Australian New Zealand Breast Cancer Trials Group's national research programme. These trials are international collaborations involving the International Breast Cancer Study Group (IBCSG). Two of the studies concern pre, peri and post-menopausal women with early breast cancer and no involved lymph glands (IBCSG 8 and 9), and two concern pre, peri and post-menopausal women with early breast cancer and involved lymph glands (IBCSG 13 and 14). In the absence of a definitive cure, the largest gains will come from optimal use of current therapies and new therapies to improve survival, and where possible, to reduce morbidity without the loss of efficacy. These four trials can realistically expect to produce important gains with potential benefit to the many women who are diagnosed with early breast cancer each year. The active accrual period for these studies is complete but all patients are currently on life long follow-up. Patients accrued to trial 8 have a clinical assessment 3 monthly to 2 years, 6 monthly to 5 years, and then annually. For trials 9, 13 and 14 women have a clinical assessment 3 monthly during year 1, 6 monthly for year 2 and then annually.Read moreRead less
Follow-up Of Women On A Randomised Clinical Trial Of Adjuvant Docetaxel And Doxorubicin For Node Positive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$113,250.00
Summary
This project is testing the use of a drug docetaxel in the post-operative (adjuvant) treatment of women with breast cancer and involved lymph nodes (N+). Until recently the drug doxorubicin was the most active chemotherapy drug for breast cancer, but more recently a new group of chemotherapy drugs called taxanes were identified. One taxane called docetaxel may be even more effective than doxoubicin. Using available treatments that include doxorubicin based chemotherapy, approximately half the wo ....This project is testing the use of a drug docetaxel in the post-operative (adjuvant) treatment of women with breast cancer and involved lymph nodes (N+). Until recently the drug doxorubicin was the most active chemotherapy drug for breast cancer, but more recently a new group of chemotherapy drugs called taxanes were identified. One taxane called docetaxel may be even more effective than doxoubicin. Using available treatments that include doxorubicin based chemotherapy, approximately half the women with N+ breast cancer experience recurrence of their cancer. It is therefore important to test whether the inclusion of docetaxel in adjuvant therapy can reduce relapses. If docetaxel is to be included, it is also important to test whether it is best to combine it with doxorubicin at the same time (which for safety reasons requires the doses of each drug to be reduced), versus giving them sequentially at full dose. Currently, docetaxel is not approved nor funded for use in early breast cancer in Australia. There are several international trials testing the inclusion of taxanes in the adjuvant therapy of breast cancer. However this trial stands out, because all the women in the trial receive chemotherapy of at least 6 months. In some other trials, testing the possible benefit of adding a taxane, women in the control treatment group (who were randomised not to receive the taxane) received only 3 months of treatment, which makes it difficult to distinguish between longer treatment or addition of the taxane drug. This trial has completed international recruitment of 2890 women who will be carefully followed for 10 years. Australian and New Zealand centers recruited 20% of the women in the trial. After the women have been followed-up for 5 years the results of this trial will be analysed, presented and published and should provide reliable evidence about the potential benefit of adding docetaxel into adjuvant chemotherapy.Read moreRead less
Clinical Trial Of Adjuvant Docetaxel And Doxorubicin For Node Positive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$185,135.00
Summary
This project is investigating the optimal use of docetaxel and doxorubicin in the treatment of women with breast cancer and involved lymph nodes (N+). Every year 3000 women in Australia, and over 400,000 worldwide are newly diagnosed with N+ breast cancer. Using available treatments more than 60% of these (5 per day in Australia, 4,500 each week worldwide) will die from breast cancer. The efficacy of adjuvant chemotherapy in early breast cancer is well established by the international overview c ....This project is investigating the optimal use of docetaxel and doxorubicin in the treatment of women with breast cancer and involved lymph nodes (N+). Every year 3000 women in Australia, and over 400,000 worldwide are newly diagnosed with N+ breast cancer. Using available treatments more than 60% of these (5 per day in Australia, 4,500 each week worldwide) will die from breast cancer. The efficacy of adjuvant chemotherapy in early breast cancer is well established by the international overview conducted by the Early Breast Cancer Trialist's Collaborative Group (EBCTCG). They have demonstrated the efficacy of adjuvant chemotherapy on reducing mortality and recurrence rates, but current regimens are far from optimal. Docetaxel (Taxotere), a new agent, has effectiveness and manageable side effects in the treatment of advanced breast cancer patients, and can plausibly improve outcomes for patients with early N+ breast cancer by optimal integration into current adjuvant chemotherapy regimens. This clinical trial is designed to compare whether it is advantageous to use docetaxel and-or doxorubicin in combination or sequentially with other currently available chemotherapy drugs.Read moreRead less
Detection Of Metastases In Sentinel Nodes From Patients With Breast Cancer Using Proton Magnetic Resonance Spectroscopy
Funder
National Health and Medical Research Council
Funding Amount
$186,372.00
Summary
The objective is to develop magnetic resonance spectroscopy (MRS) for the rapid and accurate intra-operative detection of cancer cells in sentinel lymph nodes from breast cancer patients. Accurate intra-operative diagnosis of cancer in lymph nodes will enable informed decisions to be made regarding surgery and therapy and reduce the morbidity associated with complete clearance of axillary nodes. Using current histopathological techniques (frozen section) this is not possible. Proton MRS can dete ....The objective is to develop magnetic resonance spectroscopy (MRS) for the rapid and accurate intra-operative detection of cancer cells in sentinel lymph nodes from breast cancer patients. Accurate intra-operative diagnosis of cancer in lymph nodes will enable informed decisions to be made regarding surgery and therapy and reduce the morbidity associated with complete clearance of axillary nodes. Using current histopathological techniques (frozen section) this is not possible. Proton MRS can detect chemicals in malignant cells in lymph nodes with a greater sensitivity than histology and can detect micrometastases in 20 minutes. The MR diagnostic information can be obtained from fine needle biopsies (FNB) making the technique eminently suitable for rapid intra-operative diagnosis. The FNB technique has been shown to be a rapid and accurate method for the assessment of breast lesions, distinguishing benign lesions and invasive cancer with a sensitiviy and specificity of 95% and 96%, respectively. Here we propose to evaluate the use of MRS for the rapid and accurate assessment of sentinel nodes from breast cancer patients. Two blinded studies will be conducted comparing the MRS chemical fingerprints with serial section histopathological data. To evaluate the clinical significance of the MRS diagnosis, all patients will be entered into a prospective study correlating the MRS data with recurrence of disease within 3 and 5 year periods.Read moreRead less
A Trial Of Surgery Versus Surgery Plus Adjuvant Radiotherapy In Patients With Resected Nodal Metastatic Melanoma.
Funder
National Health and Medical Research Council
Funding Amount
$305,000.00
Summary
Skin cancer is extremely common in Australia but usually presents early and is highly curable. Malignant melanoma is the third commonest skin cancer, however is the most lethal. When melanoma spreads away from its primary site on the skin it most frequently presents as a lump in the regional node basin (lymph node metastases). The region containing malignant lymph nodes (or glands) is dependent on where the primary melanoma occurred on the skin. Thus a primary melanoma on the arm or chest would ....Skin cancer is extremely common in Australia but usually presents early and is highly curable. Malignant melanoma is the third commonest skin cancer, however is the most lethal. When melanoma spreads away from its primary site on the skin it most frequently presents as a lump in the regional node basin (lymph node metastases). The region containing malignant lymph nodes (or glands) is dependent on where the primary melanoma occurred on the skin. Thus a primary melanoma on the arm or chest would be expected to spread to nodes in the axilla (armpit) or on the leg to the groin, or on the face to the neck. The standard treatment is surgery (lymphadenectomy, therapeutic lymph node dissection) to remove the malignant nodes, and is usually very effective treatment. However some patients suffer recurrence of the melanoma in the region of the lymph node surgery which can become difficult to control. Early radiotherapy has been variably used soon after the lymph node surgery (called adjuvant radiotherapy as all the known cancer has been removed by surgery) to try and reduce the risk of the melanoma regrowing in the region of the surgically removed (completely resected) nodes. This trial is designed to answer the question as to whether the addition of radiotherapy to the region of lymph node surgery does improve outcomes for patients with this diagnosis. These outcomes include potentially reducing the rate of recurrence of melanoma in the region of the lymph node surgery, finding out the difference in the frequency and severity of side effects for each of the treatments (surgery versus surgery plus radiotherapy) and as a result whether patients on the whole have any difference in their quality of life. The trial will also study what signs in the pathology specimen taken at the time of the operation might indicate when radiotherapy would be best employed. The trial aims to accrue 270 patients over 4 years from multiple centres around Australia and New Zealand.Read moreRead less
The Role Of Na-Ca Exchange Current In Cardiac Pacemaker Cells
Funder
National Health and Medical Research Council
Funding Amount
$263,100.00
Summary
The heart rate is controlled by a small group of pacemaker cells within the heart. The pacemaker cells fire spontaneously and this intrinsic rate is modified by the sympathetic and parasympathetic nerves of the autonomic nervous system. We are studying a new current in the pacemaker cells which helps to control the firing rate. This new current is controlled by the intracellular calcium inside the cells so we are also studying the way in which intracellular calcium changes when the autonomic ner ....The heart rate is controlled by a small group of pacemaker cells within the heart. The pacemaker cells fire spontaneously and this intrinsic rate is modified by the sympathetic and parasympathetic nerves of the autonomic nervous system. We are studying a new current in the pacemaker cells which helps to control the firing rate. This new current is controlled by the intracellular calcium inside the cells so we are also studying the way in which intracellular calcium changes when the autonomic nervous system is active. This project will provide new insights into the function of this small group of critical cells and may allow treatment of some cardiac arrhythmias without the expense and surgery involved in the use of artificial pacemakers.Read moreRead less