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.
Determining recurrence risk in breast cancer is crucial, as more than half of all recurrences occur after 5 years. However, optimal management of breast cancer is hampered by the challenges in finding rational preventative and predictive targets. Our vision is to find targets responsible for progenitor cell expansion, as candidates for prevention, and to find markers of relapse, to predict early versus late responders to therapy.
The Oligoadenylate-RNAseL Pathway May Provide A Specific And Low Toxicity Approach To Therapy For Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$439,314.00
Summary
We have discovered that a pathway used to fight viral infections can be triggered to produce massive cell death in the mammary gland. We hope to be able to trigger this response in breast cancers through the strategic combination of available drugs. If successful this project will establish a new therapeutic strategy for breast cancer.
Reducing The Burden Of Breast Cancer Through Precision Prevention, Targeted Treatment And Enhanced Survivorship
Funder
National Health and Medical Research Council
Funding Amount
$1,491,192.00
Summary
Breast cancer affects 1 in 8 Australian women. Of all the cancers, breast cancer results in the largest number of years of healthy life lost from death and illness. My research will reduce this unacceptable burden of breast cancer for women and their families. Spanning prevention, through treatment to survivorship, it will facilitate reduced breast cancer incidence, more effective treatments and enhanced understanding of the effects of new treatments on ovarian function and fertility.
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
Characterisation Of A Novel Oncogene In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,118,325.00
Summary
Breast cancer affects 1 in 8 women in Australia. Cancer cells are able to spread to other sites in the body by a process known as metastasis which is the leading cause of breast cancer death. We have identified a gene which controls breast cancer metastasis and thereby may affect disease outcome. This grant aims to elucidate the mechanisms by which this gene regulates breast cancer metastasis.
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.
SOFT And TEXT Premenopausal Randomised Adjuvant Endocrine Breast Cancer Trials.
Funder
National Health and Medical Research Council
Funding Amount
$722,380.00
Summary
SOFT and TEXT trials enrolled premenopausal women with hormone-sensitive early breast cancer to assess if post-operative hormone treatment that included ovarian function suppression plus tamoxifen, or an aromatase inhibitor exemestane, could improve outcomes. Initial results indicate fewer breast cancer recurrences with the treatment combination of ovarian suppression plus exemestane as compared with tamoxifen, and follow-up of women in these trials can show if overall survival can be improved.