Our breast cancer research

Our breast cancer research

L-R: Garvan cancer researchers Prof Sue Clark, Dr Fatima Valdes Mora, Dr Liz Caldon, Dr Samantha Oakes, Dr David Gallego-Ortega, Dr Andrew Burgess, Prof Chris Ormandy, A/Prof Alexander Swarbrick, A/Prof Elgene Lim.

Whole-genome sequencing gives Garvan’s breast cancer research teams an unparalleled ability to undertake whole-genome sequencing of breast tumours, vastly increasing our understanding of this disease and leading to better, safer, more effective personalised therapies.

Researchers in our Bone Biology theme are also studying how to stop the spread of breast cancer to the skeleton, where it causes bone destruction and becomes incurable, and researchers in our Genomics and Epigenetics theme are looking at ways to improve drug response in breast cancer patients with a poor prognosis. 

We're also running a series of clinical trials covering various stages of breast cancer

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Key areas of investigation

L-R: Dr David Gallego-Ortega, Prof Chris Ormandy<br>and Dr Samantha Oakes
L-R: Dr David Gallego-Ortega, Prof Chris Ormandy
and Dr Samantha Oakes

Resistance to anti-estrogen therapies

Estrogen receptors (ER) drive cancer growth in 70% of all breast cancers and drugs that target the ER pathway, such as Tamoxifen and aromatase inhibitors, have been very successful in the management of ER positive cancers. Relapse, however, remains an issue.

‘We are seeing that ELF5 may be behind two key features of ER positive cancers when they spread – escape from control by anti-estrogen therapy and metastasis.’ Professor Chris Ormandy

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A/Prof Alexander Swarbrick
A/Prof Alexander Swarbrick

The ‘off-switch’ for triple negative breast cancer

Patients with so-called triple negative breast cancers – the 15% of breast cancers that do not have either estrogen (ER) or progesterone (PR) receptors, and do not overexpress the HER2 protein – are younger and have a higher risk of relapse than those with other subtypes of breast cancer.

Personalised medicine aims to develop treatment tailored to each patient. Progress in personalised breast cancer treatment requires the development of new therapies for underserved breast cancer patients and new tests or biomarkers that can identify the most appropriate treatment for each breast cancer patient.’ Associate Professor Alexander Swarbrick

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Prof Sandra O’Toole and A/Prof Alexander Swarbrick
Prof Sandra O’Toole and A/Prof Alexander Swarbrick

Genetics of breast cancer metastasis

Associate Professor Swarbrick and his team are looking at the genes that control breast cancer metastasis and drug response. To metastasise, breast cancer cells must leave the breast, travel through the circulation and invade a distant organ. Once there, cells must adapt and survive and while most cancer cells will die in a new hostile environment, in many cases some cells eventually grow causing metastatic tumours.

‘To design better therapies for metastatic breast cancer, we first must understand the ways in which breast cancers evolve during metastasis and evade therapy.’ Associate Professor Alexander Swarbrick

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A/Prof Elgene Lim, with (L-R) Dr Christine Chaffer<br>and Dr Liz Caldon.
A/Prof Elgene Lim, with (L-R) Dr Christine Chaffer
and Dr Liz Caldon.

Sensitising breast cancer to endocrine therapies

The vast majority of breast cancers express steroid hormone receptors, including the estrogen, progesterone and androgen receptors. Therapies that target the estrogen receptor have transformed the care of patients with these cancers. However, a significant minority of such patients develop resistance to these therapies and relapse from their cancer. There is a critical need to identify new treatments and strategies to overcome treatment resistance to endocrine therapy.

‘As a clinician-scientist, I invite patients to be research partners with Garvan and access the precinct’s state-of-the-art research infrastructure, through participation in clinical trials of novel therapies, and through the provision of their tissue that is in excess of diagnostic requirements for research projects.’ Associate Professor Elgene Lim

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Prof Peter Croucher
Prof Peter Croucher

Cancer metastasis in bone

Bone Biology researchers are also investigating the bone diseases, including osteoporosis, resulting from common cancers that grow in bone, or spread to bone such as breast and prostate cancer. Research has shown that advanced breast and prostate cancers, which have travelled to the bone and myeloma (a cancer which forms in the bone marrow) have dramatic effects on the skeleton, breaking it down or causing bone to form where it shouldn’t.

‘Our research has shown that the bone’s own dynamic process of building up and breaking down bone can send signals to cancer cells inside it, to stay dormant or become active. This has led us to think in a whole new way about treating bone metastasis – and there are two particularly promising treatment approaches.’ Professor Peter Croucher, Head, Bone Biology Division.

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Prof Sue Clark
Prof Sue Clark

Hormone-Resistant Breast Cancer

As 70% of breast cancers are classified as estrogen receptor (ESR1) positive, the majority of patients receive some form of long-term hormone therapy to inhibit the ESR1-signalling network on which their tumours are dependent. Although this treatment reduces the risk of disease recurrence, half of these patients will acquire drug resistance leaving their cancer to spread – to the bone, brain, lung and liver – ruling out surgical intervention in most cases.

‘Critically, there are epigenetic modifying drugs that are currently in clinical trials to restore drug sensitivity in other cancers by reversing the epigenetic profile of a drug-resistant tumour. We are looking to repurpose these drugs for patients who are predicted to fail on hormone therapy to extend drug response.’ Professor Sue Clark

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National and International Collaborations

  • University of Adelaide, Australia
  • Cancer Research UK Cambridge Institute, UK
  • University of Cambridge, UK
  • Cardiff University, UK
  • Chris O’Brien Lifehouse, Sydney, Australia
  • Dana-Farber Cancer Institute, Boston, USA
  • Monash University, Melbourne, Australia
  • Oklahoma Medical Research Foundation, Oklahoma, USA
  • Otago University, Dunedin, New Zealand
  • Peter MacCallum Cancer Centre, Melbourne, Australia
  • Princeton University, New Jersey, USA
  • Royal Prince Alfred Hospital, Sydney, Australia
  • University of California, San Francisco, USA
  • University of Melbourne, Australia
  • University of Queensland, Brisbane, Australia
  • Weill Cornell Medical College, New York, USA
  • Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.