Progesterone Regulation Of Epithelial Expansion In The Normal Human Breast
Funder
National Health and Medical Research Council
Funding Amount
$556,393.00
Summary
The ovaries play a pivotal role in breast cancer. Progesterone increases breast cancer risk, and this is likely to be a subversion of its role in the normal breast, which is to participate in the normal expansion of the epithelial cells during the menstrual cycle, but how it does this is unknown. We will explore how progesterone influences cell types in the breast similar to those that become cancerous. This will uncover potential targets for prevention and treatment.
Role Of SOCS3 In Mammary Gland Development And Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$224,278.00
Summary
We are studying the role of a family of inhibitory molecules (SOCS) in breast tissue; these proteins have been established to have critical roles in the immune system and in regulating growth of the entire animal. We have demonstrated that one member of this family can block the action of the prolactin hormone and have recently obtained evidence that another member of this family, SOCS3, affects survival of breast cells. Furthermore, this protein leads to increased growth when overexpressed in b ....We are studying the role of a family of inhibitory molecules (SOCS) in breast tissue; these proteins have been established to have critical roles in the immune system and in regulating growth of the entire animal. We have demonstrated that one member of this family can block the action of the prolactin hormone and have recently obtained evidence that another member of this family, SOCS3, affects survival of breast cells. Furthermore, this protein leads to increased growth when overexpressed in breast cells. We propose to define the normal role of this gene in mouse mammary tissue and to examine the consequences of expressing the gene at high levels in the mammary glands of mice. Inappropriate expression of this gene may predispose humans to breast cancer. SOCS3 expression will be directly studied in a cohort of primary invasive breast cancers with associated clinical outcome data, to determine whether it has a role as a potential prognostic marker.Read moreRead less
Tailored Treatments For Premenopausal Patients With Endocrine Responsive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$257,250.00
Summary
For women under 50 years with hormone receptor positive (ER+) breast cancer, adjuvant treatment with chemotherapy, tamoxifen and ovarian ablation are each effective and reduce recurrence. Combining two treatments is more effective than one, although it is uncertain if combining three provides extra benefit. Ovarian ablation by surgery or radiation is permanent, but reversible ovarian suppression by injections is now available. Three international trials called SOFT, TEXT and PERCHE have been des ....For women under 50 years with hormone receptor positive (ER+) breast cancer, adjuvant treatment with chemotherapy, tamoxifen and ovarian ablation are each effective and reduce recurrence. Combining two treatments is more effective than one, although it is uncertain if combining three provides extra benefit. Ovarian ablation by surgery or radiation is permanent, but reversible ovarian suppression by injections is now available. Three international trials called SOFT, TEXT and PERCHE have been designed for adjuvant therapy of premenopausal women with ER+ breast cancer. These trials take into account regional-country variations in medical practice and different patient choices in this setting. SOFT is for very young women and tests the benefit of adding ovarian suppression in a woman who has received chemotherapy, with tamoxifen planned, but who has not gone into menopause after chemotherapy. The trial also tests if substituting a newer drug called exemestane for tamoxifen, combined with ovarian function suppression is more effective. TEXT is for women who would ordinarily be treated with ovarian suppression plus tamoxifen. The TEXT trial also tests substitution of exemestane for tamoxifen. Exemestane is an aromatase inhibitor. Aromatase inhibitors lower oestrogen levels, but only work if the ovaries are inactive. Recent trials in post menopausal women show aromatase inhibitors are more effective than tamoxifen, and we aim to replicate that improvement in younger women by combining exemestane with ovarian suppression. PERCHE is for women in whom the benefit of chemotherapy is uncertain, for example those with limited or no spread to lymph nodes. All women receive combined endocrine treatment with ovarian suppression plus tamoxifen, and are randomised to receive in addition, either chemotherapy or no chemotherapy, to see if results differ.Read moreRead less
Tailored Treatments For Premenopausal Women With Endocrine Responsive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$299,213.00
Summary
For women <50yrs with ER+ breast cancer adjuvant treatment (AT) with chemotherapy (CT), tamoxifen and ovarian function suppression (OFS) are each effective and reduce recurrence. Combining 2 treatments is more effective than 1, but it is unclear if combining 3 provides any extra benefit. 2 trials,SOFT and TEXT, aim to answer this question. SOFT tests the benefit of adding OFS for very young women who remain premenopausal after CT, TEXT is for women who should receive OFS from the start of AT.
Cognitive Effects Of Adding Ovarian Function Suppression To Adjuvant Hormonal Therapy In Premenopausal Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$301,431.00
Summary
There is mounting evidence that potentially curative treatment for breast cancer might, in some women, have an adverse effect on their subsequent cognitive function i.e. their memory and ability to think clearly. Thus it is important that when new treatments are being tested, the testing includes collecting information on the effect of the new treatment on a woman's cognitive function. There is currently an ongoing large international study examining whether suppressing ovarian function (and thu ....There is mounting evidence that potentially curative treatment for breast cancer might, in some women, have an adverse effect on their subsequent cognitive function i.e. their memory and ability to think clearly. Thus it is important that when new treatments are being tested, the testing includes collecting information on the effect of the new treatment on a woman's cognitive function. There is currently an ongoing large international study examining whether suppressing ovarian function (and thus decreasing oestrogen levels) in women having treatment for breast cancer will improve their outcomes. However,it is known that oestrogen is important for normal cognitive functioning in premenopausal women so there is some concern that dropping the oestrogen levels in this way might cause impairment in cognitive function. In this sub-study we will compare the cognitive function of women having ovarian function suppression with those who do not, to determine if there are any differences. We will also examine how this might affect quality of life.Read moreRead less
Two Recently Identified Calcium Transporters In Lactation And During Mammary Epithelial Cell Apoptosis.
Funder
National Health and Medical Research Council
Funding Amount
$465,115.00
Summary
The transport of calcium into milk is a key event in human health. In addition to its importance in neonatal nutrition, the way breast cells regulate calcium also has implications in breast cancer, as well as the modification of proteins important in immunity, and the activity of biopharmaceuticals. This grant will determine how two specific calcium transporters regulate calcium levels in the breast and their respective roles in cellular processes important in normal function and in disease.
The Role Of The EphA1 In The Normal Epithelial Organs And In Epithelial Tumour Progression.
Funder
National Health and Medical Research Council
Funding Amount
$564,500.00
Summary
The Eph family of proteins were initially found to be important in normal development. In humans this corresponds to the first 12 weeks of pregnancy. In parallel with these studies, other work provided evidence of abnormally high levels of these proteins in a number of human cancers. More recent evidence suggests that these proteins have important roles in the maintenance of normal tissues and in non-malignant diseases. This proposal seeks to understand how one of these proteins (EphA1) works in ....The Eph family of proteins were initially found to be important in normal development. In humans this corresponds to the first 12 weeks of pregnancy. In parallel with these studies, other work provided evidence of abnormally high levels of these proteins in a number of human cancers. More recent evidence suggests that these proteins have important roles in the maintenance of normal tissues and in non-malignant diseases. This proposal seeks to understand how one of these proteins (EphA1) works in the cells which form the skin, liver, kidneys, breast and prostate. These cells also form the lining of the mouth, stomach, bowel and lungs. Understanding how the EphA1 protein and other members of this family cooperate to control the development and maintenance of these organs will allow us to determine whether this protein might be involved in congenital defects and diseases in these organs (such as kidney failure, cirrhosis of the liver and skin diseases). A second main aim of this project is to explore further the observation that Eph proteins are abnormally highly expressed in a wide rangre of human cancers. This abnormal expression is directly correlated with the tumours spreading throughout the body. EphA1 is abnormally highly expressed in cancers of the bowel, lung, breast and prostate. These are the commonest cancers in man and some of the most difficult to treat. The work proposed asks how EphA1 contributes to the development and progression of these cancers. These results will have very direct implications for the development of therapies which target the EphA1 protein.Read moreRead less
Macrophages In Developmental Programming Of Reproductive Health
Funder
National Health and Medical Research Council
Funding Amount
$532,386.00
Summary
Programming of reproductive health in women begins long before sexual maturity. Development during childhood, puberty and adulthood produces a fully functional reproductive system capable of conceiving, gestating and nurturing a child. This project will investigate the role of immune cells known as macrophages in the reproductive system, and investigate how their disruption might influence developmental programming and have lifetime consequences for the reproductive health of the individual.
Incidence And Prognosis Of Metastatic Breast Cancer: A Population-based Data Linkage Study
Funder
National Health and Medical Research Council
Funding Amount
$97,700.00
Summary
This project will provide the first Australian population-based estimates of metastaticbreast cancer (MBC) incidence and survival in women with an initial diagnosis of early stage cancer that reflect current treatment practices. This evidence will help: women with MBC and their clinicians to make decisions about treatment and plan supportive care; researchers planning trials of MBC therapies, and future planning of cancer services.