Breast Biology and Cancer Unit 

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Breast cancer is the most prevalent type of cancer among women, with approximately 13,000 new cases diagnosed each year in Australia. Our Breast Biology and Cancer Unit are researching the basis of the cellular and molecular mechanisms that underpin this high incidence of breast cancer. We use a variety of mouse models, together with human breast tissue, to study how key risk factors, including menstrual cycling and breast density, lead to increased susceptibility of the mammary gland to cancer. We focus on how these risk factors affect the ability of the immune system to protect this unique tissue against carcinogens and other cancer initiating factors. The overarching objective of our research is to provide therapies that reduce a woman’s lifetime risk of developing breast cancer.

In addition to studies on breast cancer susceptibility, we also conduct mastitis research. Mastitis is a common inflammatory disease in lactating women that causes pain, fever, low milk supply and leads many to cease breastfeeding. This research explores the cellular mechanisms that lead to inflammation, and investigates potential therapies to quickly and effectively stop the symptoms of mastitis.

The Breast Biology and Cancer Unit was established at the BHI in 2011 as part of the collaborative links established at The Queen Elizabeth Hospital (TQEH).

Research projects for Honours, Masters and PhD students are available in our laboratory – please read the Projects available and contact wendy.ingman@adelaide.edu.au to discuss these further.

Other related websites: INFORMD (INformation FORum on Mammographic Density) and the Australian Breast Cancer Research website.

Researchers

Students

Student Alumni (since 2017)

NameDegreeYear AwardedThesis titleSupervisors
Vahid AtashgaranPhD, The University of Adelaide. Dean's Commendation for Doctoral Thesis Excellence.2018Hormone and transcription factor regulation of cytokines in the mammary glandIngman W, Dasari P, Barry S
Siti Noor DinPhD, The University of Adelaide.2017Effect of C1q null mutation on mammary gland developmentIngman W, Robertson S

 

Breast Cancer Risk and Prevention
Breast cancer places an incredible burden on Australian women. Every year, around 18,000 Australian women are diagnosed with breast cancer alone - a disease that devastates women's lives and is often fatal. If we are to prevent and treat breast cancer, we must better understand how the disease develops. Breast density (also known as mammographic density) is the percentage of white and bright regions on a mammogram. Breast density is not related to how breasts look or feel and can only be assessed by mammogram. Forty three percent of women have "Heterogenously Dense" or "Extremely Dense" breasts, which together are termed "high breast density". High breast density is both an independent risk factor for breast cancer and masks cancers on a mammogram. Combined, these two distinct phenomena lead to increased incidence, delayed diagnosis, more aggressive tumours, and a 90% increased risk of breast cancer-associated death in women with high breast density. There is exciting potential for breast density to become a widespread health assessment tool, used to identify the women most at risk of breast cancer in order to intervene early and reduce that risk. Our research is the first to demonstrate a causal role for immune system signalling in breast density and the associated cancer risk. Using a unique human biobank of paired high and low density breast tissue samples, together with transgenic mouse models, we demonstrated that pro-inflammatory protein C-C Motif Chemokine Ligand 2 (CCL2) is a biological driver of both high breast density and increased risk of cancer. This study opens the door for new approaches to reduce breast cancer risk through use of anti-inflammatory drugs in women with dense breasts.

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Improving Breast Cancer Treatment
Breaking immune tolerance in triple negative breast cancer: Failure of the body's immune system to attack a threat such as a mutated cell is known as immune tolerance, and is one of the key hurdles to overcome in both treating breast cancer and preventing its recurrence. Our laboratory has identified a new biological pathway active in breast cancer involving a protein called C1q, which can be targeted to break this tolerance. The aim of this project is to capitalize on this discovery to develop a new approach to breaking tolerance in triple negative cancer, a very aggressive subtype of breast cancer which is notoriously difficult to treat. Exploring the impact of menstrual cycling on personalised medicine for premenopausal breast cancer patients: Gene expression profiling of breast cancer is a technology increasingly being adopted in the clinic as a personalised medicine approach to tailor treatment to individual patients. However, an underappreciated factor in premenopausal breast cancer diagnosis is that oestrogen and progesterone fluctuate dramatically during the menstrual cycle, and these hormones are likely to affect gene expression. This research aims to determine whether fluctuation in oestrogen and progesterone associated with different stages of the menstrual cycle significantly affects gene expression profiles in breast cancers from premenopausal women. We will examine gene expression profiles in paired biopsy and surgical breast cancer tissue samples taken from women undergoing treatment at The Queen Elizabeth Hospital, and investigate how menstrual cycle stage in the two samples affects breast cancer subtype.

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Mastitis and Lactation Insufficiency
Lactation mastitis is an inflammatory breast disease affecting 17-27% of Australian breastfeeding women that causes pain, fever and low milk supply. The challenges posed by this disease lead many women to use supplementary formula, or cease breastfeeding altogether leaving their infants at increased risk of respiratory and gastrointestinal diseases as babies, and non-communicable diseases including heart disease, obesity, diabetes, cancer, allergies, asthma, mental illness and chronic lung, liver and renal diseases as both children and adults. Our recent research has suggested that macrophages play a role in development of this disease. Our current research pursues new knowledge in how disease state develop in the breast. We explore revolutionary new concepts of how immune cells function in the breast, and how these cells affect breast disease development.

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For a list of all publications please visit A/Prof Wendy Ingman’s University of Adelaide Researcher Profile.
The gut microbiome: a new player in breast cancer metastasis

Ingman WV. The gut microbiome: a new player in breast cancer metastasis. Cancer Research; 2019. 79(14):3539-3541.

Pubmed Link:  https://www.ncbi.nlm.nih.gov/pubmed/31308136
InforMD: A new initiative to raise public awareness about breast density

Hugo HJ, Zysk A, Dasari P, Britt K, Hopper JL, Stone J, Thompson EW, Ingman WV. InforMD: A new initiative to raise public awareness about breast density. eCancer;  2018. 12:807.

Pubmed Link:  https://www.ncbi.nlm.nih.gov/pubmed/29492101
Dissecting the biology of menstrual cycle-associated breast cancer risk

Atashgaran V, Wrin J, Barry SC, Dasari P, Ingman WV. Dissecting the biology of menstrual cycle-associated breast cancer risk. Frontiers in Oncology; 2016. 6:267.

Pubmed Link:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5183603/
CCL2-driven inflammation increases mammary gland stromal density and cancer susceptibility in a transgenic mouse model

Sun X, Glynn DJ, Hodson LJ, Huo C, Britt K, Thompson E, Woolford L, Evdokiou A, Pollard JW, Robertson SA, Ingman WV. CCL2-driven inflammation increases mammary gland stromal density and cancer susceptibility in a transgenic mouse model. Breast Cancer Research; 2017. 19(1):4.

Pubmed Link:  https://www.ncbi.nlm.nih.gov/pubmed/28077158
Hormonal modulation of breast cancer gene expression: implications for intrinsic subtyping in premenopausal women

Bernhardt SM, Dasari P, Walsh D, Townsend AR, Price TJ, Ingman WV. Hormonal modulation of breast cancer gene expression: implications for intrinsic subtyping in premenopausal women. Frontiers in Oncology; 2016. 6:241.

Pubmed Link:  https://www.ncbi.nlm.nih.gov/pubmed/27896218
Inflammatory mediators in mastitis and lactation insufficiency

Ingman WV, Glynn DJ, Hutchinson MR. Inflammatory mediators in mastitis and lactation insufficiency. Journal of Mammary Gland Biology and Neoplasia; 2014, 19:161–167.

Pubmed Link:  https://www.ncbi.nlm.nih.gov/pubmed/24961655

BHI Collaborators: Andreas Evdokiou, Tim Price, Amanda Townsend, Ken Pittman, David Walsh, Tim Proudman

External Collaborators: Rik Thompson, University of Melbourne; Fiona Pixley, University of Western Australia;  Kara Britt, University of Melbourne; Sarah Robertson, University of Adelaide; Simon Barry, University of Adelaide; Mark Moore, Calvary North Adelaide Hospital