Our research focuses on the molecular and cellular basis of breast cancer devlopment, improving the way we predict the risk of relapse, and finding better ways to treat this disease.

Breast tumour biomarkers

New prognostic and predictive  breast cancer biomarkers

We now know that breast cancer is not a single disease, but a collection of entities that vary widely in their appearance under the microscope, genetic makeup, cellular composition and clinical presentation. This variability, or heterogeneity, exists not only between cancers, but also within each cancer. For example, there may be patchy areas of very tightly packed cancer cells and necrosis (dead or dying tissue that is hypoxic), which can alter the uptake of drugs or immune cells into those areas; and certain genetic alterations may be present in some parts of a tumour but not others. This immense heterogeneity can make it very difficult to predict how an individual cancer will respond to particular therapies.

Ideally, each patient’s treatment should be personalised according to accurate predictions about the risk of relapse, and which therapies are likely to achieve the best results.

The MBP group is part of an international research effort focused on bringing this personalised model of cancer care into clinical practice. Together with traditional histopathology assessment and immunohistochemistry, we also apply cutting-edge molecular profiling technologies and try to correlate molecular tumour features with patient outcomes. A lot of our work involves extracting DNA and RNA from patient tissues, and applying technologies like next-generation sequencing and DNA copy-number analysis.

We are excited about our work in this area with our collaborators from QIMR Berghofer, which is focused on accurately measuring tumour expression of multiple genes associated with aggressive clinical behaviour at the same time to predict the most optimal chemotherapy regimen for each patient. We hope that this work will lead to a new diagnostic test to inform clinical management.

Team members: Dr Jodi Saunus, Lynne Reid, A/Prof Margaret Cummings, Dr Peter Simpson, Dr Amy McCart Reed, Dr Fares Al-Ejeh, Dr Jamie Kutasovic

For more information please contact Dr Jodi Saunus

Familial breast cancer

Computational network modelling to understand tumour development in familial breast cancer

Team members: Dr Peter Simpson, Dr Andrew Dalley,  Dr Sriganesh Srihari, Prof Kum Kum Khanna

For more information please contact Dr Peter Simpson

Lobular breast cancer

Invasive Lobular Cancer (ILC) is the most common ‘special type’ of breast cancer, accounting for up to 15% of all cases. ILCs have a characteristic diffuse morphology and routinely lose expression of the adhesion molecule, E-cadherin.

ILCs are mostly oestrogen receptor positive, which allows treatment of these patients with anti-oestrogen therapies, for example, Tamoxifen. An ILC diagnosis is generally associated with a good short term prognosis, however over the longer term (~20 years) there is increasing evidence to suggest that ILC patients have a worse outcome than patients with the more common subtype of breast cancer (Invasive Carcinoma, no special type). 

There are special morphological subtypes of ILC (including those of mixed phenotypes) and the team is also working toward understanding the molecular heterogeneity of these tumours. ILC show a unique pattern of metastatic progression, and our genomics studies will also elucidate the mechanistic drivers of this so called ‘organotropism’. 

Team members: Dr Peter Simpson, Dr Amy Reed, Samir Lai, Renique Males, Llana Dedina

For more information please contact Dr Peter Simpson

Metaplastic breast cancer

Metaplastic breast carcinomas (MBC) are named from the Greek word ‘metaplasia’, meaning change in form, and typically these tumours present with a mix of malignant cell types (mesenchymal and epithelial elements).

MBC account for <5% of all invasive breast cancers; in other words, they are very rare. However, these tumours can be very aggressive and contribute significantly to global mortality from breast cancer. Current clinical diagnostic criteria are regarded as inadequate for this subtype. A better understanding of Metaplastic breast cancer (and indeed other triple-negative, basal-like breast cancers) will help us to develop more effective therapies.

We have established the Asia-Pacific Metaplastic Breast Cancer Consortium (APMBCC) to facilitate the assembly of a large cohort of these rare tumour samples for research.

APMBCC members:

  • Dr Rin Yamaguchi (Japan)
  • Dr David Papadimos (QLD, Australia)
  • Dr Gary Tse (Hong Kong)
  • Dr Puay Hoon Tan (Singapore)
  • Dr Gavin Harris (New Zealand)
  • Dr Sandra O’Toole (NSW, Australia)
  • Prof Nirmala Pathmanathan (NSW, Australia)
  • Prof Sunil Lakhani (QLD, Australia)
  • Dr Pathma Rajadurai (Malaysia)
  • Dr Amy Reed (QLD, Australia)
  • Dr Peter Simpson (QLD, Australia)
  • Dr Nic Waddell (QLD, Australia)

For more information please contact Dr Amy Reed

Brain metastases

The Australian Institute of Health and Welfare (AIHW) predicted there would be 15,740 new cases of breast cancer in 2015. Mortality from breast cancer has decreased over the last few decades, but unfortunately around 10% of patients still succumb to their disease within 5 years. Most of these early breast cancer deaths involve the spread of cancer (metastais) to the brain.

The development of brain metastases is a very serious complication that affects more than 2000 Australian breast cancer patients each year. Many are young women with HER2+ or triple-negative disease. Prognosis depends on whether disease has also spread to other sites in the body and the subtype of the primary tumour, but unfortunately, most patients experience very challenging neurological side effects and succumb to their disease within a few years of diagnosis. Surgery, radiotherapy and sometimes chemotherapy are used to manage brain metastases currently, and while there have been advances in the way they are delivered to improve local control of disease and quality-of-life, morbidity and mortality remain very high.

There is huge energy across the spectrum of basic, translational and clinical research to address this challenging problem in our community, and researchers around the world are working hard to find new options. The MBP Group is working on several projects in this area:

  • Development of new theranostic agents using the HIRF (Herston Imaging Research Facility), located next to the UQCCR;
  • Identification of miRNA-regulated gene networks involved in the growth of breast cancer cells in the brain;
  • Investigating how tumour cell-intrinsic processes enabling the outgrowth of cancer cells in the brain are influenced by the very unique microenvironment in this organ.

Team members: Dr Jodi Saunus, Dr Priyakshi Kalita, Malcolm Lim

For more information please contact Dr Jodi Saunus

Gynaecological metastases

The most common sites of breast cancer spread, or metastasis, are the bone, lung, liver and brain; but different types of breast cancer tend to spread in specific patterns – so-called organotropic behaviour.

Invasive Lobular Carcinoma (ILC), the second most common type of breast cancer, is more likely to spread to gynaecological and gastrointestinal sites than other types of breast cancer, particularly in young women. In many cases, by the time gynaecological metastases are symptomatic, the disease has often already spread throughout multiple different organ systems (for example, the ovaries, fallopian tubes, and throughout the peritoneum). This insidious, late-presenting complication can be very challenging clinically, and many patients could benefit from earlier detection of metastatic disease so that surgical and/or oncological interventions can be initiated while cancer deposits are still small, and before they are symptomatic. 

The MBP group has an ongoing program of work to study the molecular similarities and differences between primary and metastatic cancer deposits from patients whose disease involves the gynaecological organs. We think this will improve our understanding of how and why these tumours spread in this pattern. 

The main translational aim of this research is to identify primary tumour biomarkers that can be used to predict which patients are at risk of gyanecological metastasis to identify patients who might benefit from heightened clinical surveillance (e.g. advanced imaging). 

Team members: Dr Peter SimpsonDr Amy ReedA/Prof Margaret Cummings, Dr Jamie Kutasovic, Renique Males

For more information please contact Dr Peter Simpson

Circ.BR (Circulating Biomarkers of Relapse in Breast Cancer)

Circ.Br is a prospective, longitudinal study of patients with high grade-breast tumours. The primary aim is to detect biomarkers circulating in the blood that are indicative of recurrence/relapse before it is symptomatic. Earlier detection of treatment resistance will allow therapy to be adjusted while cancer deposits are still small and manageable, and minimise exposure to treatment side-effects in patients who are unlikely to benefit. 

The ultimate goal of this study is to develop a minimally invasive ‘liquid biopsy’-based diagnostic test, but we also hope to identify new drug targets, and understand the genetic changes that underlie breast cancer progression (infographic below).

This is a collaborative study, bringing together several clinical disciplines (including surgery, radiology, pathology and oncology) as well as translational research groups. Patients with high-grade breast cancer are currently being recruited through the Royal Brisbane and Women’s Hospital, and their progress is then followed by the Circ.BR team for as long as possible up to five years.

The commitment of enrolling patients involves:

  • Donation of excess* primary breast tumour tissue from initial biopsy/surgery;

  • Donation of excess* tissue from biopsy or resection of any recurrences (where possible);

  • Donation of blood samples when attending routine clinical follow-up appointments (3-6 monthly);

  • Participation in a lifestyle and well-being questionnaire.

*tissue in excess of what is used in normal clinical diagnostic testing procedures.

Team members:  Dr Amy Reed, Colleen Niland, Kaltin Ferguson, Dr Kowsi Murugappan 

For more information please contact Dr Amy Reed

BROCADE rapid autopsy study

BROCADE - BReast Origin Cancer tissue donated After DEath

In Australia, around 20% of breast cancer patients experience disease recurrence. Once breast cancer spreads to distant sites and establishes new secondary tumours (mainly the liver, lungs, bone and brain), treatment options become very limited. 

Our vision is that breast cancer will be managed within a more personalised model of care in the future:

  • Expertise and infrastructure will be developed for detailed molecular testing of tumour biopsies and blood samples;
  • Molecular tests will predict drug sensitivity and resistance;
  • Optimal treatment regimens will be tailored to each patient, and each tumour;
  • There will be routine clinical use of targeted therapies for both primary and metastatic disease;
  • Combination treatments will be used to simultaneously target tumour growth and likely resistance pathways.

There is a huge, ongoing international effort to realise this goal, involving drug target discovery, therapeutic development and clinical testing of new agents. Researchers are constantly striving to increase the efficiency of this process – one approach is to improve access to human tumour samples for research. At the moment, breast cancer metastases are not routinely excised or biopsied - these invasive procedures are only performed if there is proven benefit for the patient; but paradoxically, efforts to discover and test the benefits often require tissue samples. In the past this dilemma has significantly limited the development of new treatments.

Detailed molecular comparison between ‘matched’ primary and metastatic tissue samples (i.e. from the same patient) can illuminate the changes that facilitate disease spread, as well as those that render the tumour sensitive or resistant to particular therapies. Another cutting-edge application for these donated tissue samples is cancer drug screening in Patient Derived Xenografts (PDX– see infographic below).

The MBP team and the Brisbane Breast Bank comprise the Brisbane node of an NBCF-funded rapid autopsy study called BROCADE. Led by Profs Robin Anderson (Peter Mac, Victoria) and Alex Swarbrick (Garvan Institute, NSW), this 5-year initiative aims to provide resources to accelerate the development of new therapeutics, and predictive biomarkers that will identify the most effective treatments for each patient. BROCADE will establish a biobank of tissues patients who consent to a rapid autopsy in the event of their death from breast cancer, and donation of tumour samples for research that will benefit future generations. PDX will be established as part of this resource. Tissue and data collected will be part of a resource for researchers nationally and internationally, subject to ethics approvals.

BROCADE is currently recruiting. Patients interested in participating should discuss this with their families, support network and doctors.

For more information please contact Amy Reed

BoNSAI

BoNSAI - Improving treatments for brain metastases through advanced imaging

BonsaiOncology R&D is flourishing at the moment, yet molecular-targeted agents are still not routinely used to manage metastatic brain disease. Historically, a heavy co-morbidity burden and misconceptions about added risk of toxicity restricted their participation in clinical trials, but this trend is beginning to change. An increasing number of clinical trials assessing the intracranial efficacy of molecular-targeted agents are being registered. Many are testing monoclonal antibodies (mAbs) that target human epidermal growth factor receptors (HERs), which have been strongly implicated in the risk of metastatic outgrowth in neuregulin-rich brain tissue. This reflects the urgency of the public health problem and is a promising sign of healthcare reform. 

Brain metastases are highly vascular, so their recalcitrance to circulating therapeutics (particularly larger drugs like mAbs) has been mainly attributed to intrinsic resistance and restricted uptake across the blood-brain-barrier. But emerging data suggest a more complex scenario in which drug bioavailability is also restricted by oedema, chaotic vascular perfusion and abnormal interstitial fluid dynamics. Paradoxically, these factors can create areas of sluggish blood flow and hypoxia in an otherwise hypervascular tumour. 

BoNSAI is a cross-sectional, observational clinical trial. Patients participating in this study will be administered with a small dose of 89Zr-pertuzumab tracer, then imaged several times over the following week to determine the uptake and retention of the tracer in brain tumours over time. The study aims to establish guidelines to predict which patients will benefit from HER2-targeted therapy, and around mAb dosing schedules for treatment of metastatic brain disease.

Team members: Jodi Saunus and Colleen Niland 

For more information please contact Jodi Saunus.

For more information about clinical intervention trials for brain metastases visit BRAINMETSBC.org

Based at the UQ Centre for Clinical Research, the Brisbane Breast Bank was originally established by Professor Lakhani in 2005, with the aim of collecting a frozen tumour sample from every patient undergoing treatment at the Royal Brisbane and Women’s Hospital.

With financial support from UQ, QIMR Berghofer, the RBWH Foundation and Australasian Biospecimen Network, as well as the cooperation and goodwill of staff from Pathology Queensland, QML and Sullivan Nicolaides Pathology, the bank has been operating for over 10 years, and has become a valuable resource for breast cancer research in Australia and abroad.

Other researchers can apply to access BBB resources, but the research is conducted on a collaborative basis, rather than as a paid service for sample provision. Conducting the research in this way enables us to be true custodians of the biospecimens and clinical data, ensuring the most efficient and meaningful use of this finite resource, and compliance with National Human Research Ethics guidelines. Requests for research collaboration and clinical samples may also come to us via National and International biobanking groups with which we are affiliated:

  • The Australian Breast Cancer Tissue Bank (ABCTB)
  • The Australasian Biospecimens Network Association (ABNA)
  • Brain Cancer Biobanking Australia (BCBA)
  • The International Cancer Genome Consortium (ICGC)

The Brisbane Breast Bank represents critical national biomedical research infrastructure and is helping to increase the relevance of breast cancer research on an international scale.

It is now more important than ever to ensure its sustainability.

What is a tissue bank?

A tissue bank (biospecimen bank, or bio-bank) is a repository of biological samples (e.g. blood products, tumour tissue), linked to data relating to sample collection and clinical history, such as whether a patient’s cancer responded to a particular treatment.

Biospecimens can be stored for decades in a variety of formats (e.g. frozen, live cell cultures or formalin-fixed). Secondary biospecimens may also be derived to further enhance the value of the samples – byproducts commonly include genetic material (DNA, RNA), digitally archived images of tissue sections and even patient-derived tumour xenografts* (PDX).

Human breast tumour samples and their byproducts are pivotal to research – for example, validating findings from experimental systems, or correlating tumour features with cancer treatments and patient outcomes. Amassing large numbers of samples gives the statistical power needed to determine whether treatments are really working, and if so, allows us to predict which patients would be most responsive to a particular therapy. Personalising cancer treatment in this way is how researchers hope to make a greater impact on breast cancer in the future.

Biobanks can distribute de-identified samples and data to research teams anywhere in the world, helping to build a critical mass that is conducive to innovation, discovery and ultimately, improved healthcare.

Despite the importance of human samples in breast cancer research, infrastructure funding is limited and the procedures for banking patient material are not currently integrated into our healthcare system.

*when human tumour tissue from a surgical specimen is implanted into an immunodeficient mouse to create a live and replenishable source of tumour material for research, and to facilitate experimental testing (e.g. of new cancer therapies). PDX models are highly valued in breast cancer research and are providing critical efficacy and safetly information to help guide patient management in the future.

Sample collections

The Brisbane Breast Bank collects biospecimens from patients undergoing treatment at the Royal Brisbane and Women’s Hospital, though patients undergoing surgery at other South East Queensland hospitals should discuss biobanking with their Surgeons and contact us if they wish to donate tissue, as alternative tissue collection arrangements are often possible.

The BBB Manager provides information on tissue donation to patients at the weekly RBWH breast unit pre-admission clinic, where breast care nurses are also present to discuss issues like rehabilitation after surgery. Patients can then take the information away and consider whether they would like to donate excess* tumour tissue, a blood sample, and make their sample identifiable* to tissue bank staff, so that it may be linked with appropriate clinical data such as treatment response. 

Breast tissue samples from patients undergoing reduction procedures are also collected as an essential source of non-cancerous ’control’ tissue. The 

Brisbane Breast Bank is also the central tissue processing site for the Brisbane node of the ‘BROCADE’ study.

If you are interested in donating tissue for research, please discuss this with your doctors, and contact us with any queries.

For more information and to donate, please contact: 

Kaltin Ferguson, Tissue Bank Manager
Email: k.ferguson2@uq.edu.au
Phone: +61 7 3346 6020

Outcomes

Tissues, secondary byproducts and data from the Brisbane Breast Bank have contributed to dozens of National and International studies, and impacted directly and indirectly on patient management. Here are a few examples:

  • More than 180 primary research papers published in the scientific literature. The networks, infrastructure and procedures established by the BBB have also paved the way for two cutting-edge clinical studies that are currently recruiting patients: Circ.Br and BROCADE.

  • Launched in 2008, the International Cancer Genome Consortium (ICGC) is a worldwide organisation with the primary goal of cataloguing all of the genetic alterations in the 50 most common human cancers, using high-resolution molecular profiling technologies like next-generation sequencing. It is hoped that this initiatve will reveal molecular subtypes of each cancer, clues about cancer development, and enable development of new therapies. The BBB contributed around 10% of the high quality breast tumour samples used in this groundbreaking study.

  • In 2014, the MBP team made a discovery that led to a Brisbane metastatic breast cancer patient being offered new treatments to improve the quality and duration of her life. Amanda had donated three secondary brain tumours to the BBB that were analysed as part of an ongoing research project. The study identified many potentially ‘targetable’ alterations in the donated tumour samples, but for the vast majority, the corresponding treatments had not yet been tested in clinical trials. Amanda’s situation was unique because the new treatments were already proven to be safe and effective, and doctors were able to offer them straight away. She defied all expectations and we are honoured that we were able to help her and her family. Read more about the story here, and the research paper here.

We are passionate about our research, raising awareness, and involving the community.

The Molecular Breast Pathology team values feedback from the community - we need to know if you think we are focusing on the right issues.

We hold annual consumer representative meetings to showcase our research and seek input on future endeavours, and we are committed to attending and contributing to community events that help raise awareness. We have presented on various aspects of our work at Pink Ribbon Breakfasts, Science week and School events, and breast cancer advocacy meetings. For more information, please contact us.

Useful links

 

To all of the patients, families, donors, doctors and other healthcare staff who have contributed to the Brisbane Breast Bank: Your support is invaluable.

Donate funds

How you can help the fight against breast cancer and help save thousands of lives

The Brisbane Breast Bank is run largely on the goodwill of individuals & organisations.

Limited funding is available to support the continued operation of this invaluable tissue bank, and so we are endeavouring to raise $1,000,000 over the next five years. This will provide the stability and sustainability required to continue accruing samples and data, and to maximise the use of the resource through collaboration with researchers from elsewhere in Australia and abroad.

Here are some examples of annual costs associated with maintaining a small biobanking operation: 

  • Staff to collect, process and store tissues - $120,000
  • Nursing staff to visit patients and collect blood samples - $90,000
  • Data management - $30,000
  • Plasticware and chemicals for processing and storing tissues - $10,000

To support the Brisbane Breast Bank and MBP group, make a difference through tax deductible donation: 

Donate tissue

The Brisbane Breast Bank collects biospecimens from patients undergoing treatment at the Royal Brisbane and Women’s Hospital, though patients undergoing surgery at other South East Queensland hospitals should discuss biobanking with their Surgeons and contact us if they wish to donate tissue, as alternative tissue collection arrangements are often possible.

For more information and to donate, please contact: 

Kaltin Ferguson, Tissue Bank Manager
Email: k.ferguson2@uq.edu.au
Phone: +61 7 3346 6020

Donate time

  • Do you feel strongly about breast cancer research, and want to help in some way?
  • Do you have particular skillsets that could be useful?
  • Would you like to fundraise for the MBP Group and Brisbane Breast Bank?
  • Would you like to attend one of our consumer rep meetings?

If the answer is yes, we'd love to hear from you.

Please contact Shari Bowker:
(07) 3346 6052
s.bowker@uq.edu.au

Our supporters

The MBP Group is very grateful for support from these individuals and organisation.

Honour Wall

  • Joy Jensen
  • Amanda Stevens

Our supporters