In the Britt laboratory, researchers are interested in understanding what mediates breast cancer risk to develop novel treatments and preventatives.
We are interested in defining:
- What changes occur within the breast during the earliest stages of cancer development.
- What mediates the protection against breast cancer that is afforded by childbearing.
- Why women with increased breast density are at an increased risk of breast cancer.
Determining the role of mammary stem cells in breast cancer risk
Women who have children (parous) have a reduced risk of breast cancer and this protection is strongest for those bearing children early. Women having children later in life are not protected against breast cancer, but instead are at an increased risk. We have developed an in vivo model to test the role of mammary stem cells in parity-induced protection. This project will determine whether a non-classical stem cell with high cancer susceptibility is responsible for mediating the protection and if it is only changed by younger, but not older, pregnancies.
Modulating the immune system in early stage breast cancer to block initiation
Breast cancer is not considered immunogenic, as its incidence is not increased in immunosuppressed patients (such as transplant patients and HIV patients). However, irrefutable data now show that the immune cell infiltrate of a breast cancer affects its growth and metastasis. Only limited data exist on the role of immune cells in the early stages of breast cancer. This project will determine whether immune changes occur early in the tumourigenic process of triple negative breast cancers, and whether this can be treated with immunotherapy to inhibit cancer development.
Finding a therapeutic option for a subset of triple negative breast cancers
Triple negative breast cancers are a poor prognosis breast cancer with limited therapeutic options, as they do not express oestrogen receptor alpha, progesterone receptors or Her2. Recent clinical studies have shown that women who have triple negative breast cancers, but express the alternate oestrogen receptor ERβ, respond well to tamoxifen. This project will use a transgenic model of triple negative breast cancer, engineered to express ERβ, to determine how tamoxifen exerts its benefits to these patients.
Developing a therapy to decrease breast density and breast cancer risk
High mammographic density (HMD) confers a significantly increased risk of breast cancer and is associated with more advanced breast cancers. Fifty per cent of the female population have moderate to high mammographic density, making it a significant risk factor for breast cancer. To determine the pathobiology underlying breast density, we have studied HMD and low mammographic density (LMD) prophylactic mastectomy tissue from non-cancer bearing women. We have also developed a novel biochamber model that allows us to grow HMD and LMD tissue in vivo and test density-modulating therapies. We have also extended this model to assess the ability of HMD tissue to drive early-stage cancer growth. We now want to use these models to test emerging density-reducing therapies, which will also reduce breast cancer risk.
Dall GV, Hawthorne S, Seyed-Razavi Y, Vieusseux J, Wu W, Gustafsson JA, Byrne D4, Murphy L, Risbridger GP, Britt KL, Estrogen receptor subtypes dictate the proliferative nature of the mammary gland. J Endocrinol. 2018 Jun;237(3):323-336.
Huo CW, Hill P, Chew G, Neeson PJ, Halse H, Williams ED, Henderson MA, Thompson EW, Britt KL. High mammographic density in women is associated with protumor inflammation. Breast Cancer Res. 2018 Aug 9;20(1):92
Dall GV, Vieusseux JL, Korach KS, Arao Y, Hewitt SC, Hamilton KJ, Dzierzak E, Boon WC, Simpson ER, Ramsay RG, Stein T, Morris JS, Anderson RL, Risbridger GP, Britt KL, SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24+ CD49fhi Mammary Stem Cell-Enriched Compartment. Stem Cell Reports. 2017 Feb 14;8(2):417-431
Dall GV, Britt KL. Estrogen Effects on the Mammary Gland in Early and Late Life and Breast Cancer Risk, Front Oncol. 2017 May 26;7:110.
Unsworth A, Anderson R, Haynes N, Britt K (2016). Two multi-color immunophenotyping panels for assessing the innate and adaptive immune cells in the mouse mammary gland. Cytometry A. 89(6):527-30.
Dall G, Risbridger G, Britt K (2016). Mammary stem cells and parity-induced breast cancer protection- new insights. J Steroid Biochem Mol Biol. 170:54-60.
Dall G, Vieusseux J, Unsworth A, Anderson R, Britt K (2015). Low dose, low cost estradiol pellets can support MCF-7 tumour growth in nude mice without bladder symptoms. J Cancer. 6(12):1331-6.
Huo CW, Waltham M, Khoo C, Fox SB, Hill P, Chen S, Chew GL, Price JT, Nguyen CH, Williams ED, Henderson M, Thompson EW, Britt KL. Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis. Breast Cancer Res. 2016 Oct 25;18(1):106.
Huo CW, Huang D, Chew GL, Hill P, Vohora A, Ingman WV, Glynn DJ, Godde N, Henderson MA, Thompson EW, Britt KL, Human glandular organoid formation in murine engineering chambers after collagenase digestion and flow cytometry isolation of normal human breast tissue single cells. Cell Biol Int. 2016 Nov;40(11):1212-1223.
Huo CW, Chew G, Hill P, Huang D, Ingman W, Hodson L, Brown KA, Magenau A, Allam AH, McGhee E, Timpson P, Henderson MA, Thompson EW*, Britt K* (2015). High mammographic density is associated with an increase in stromal collagen and immune cells within the mammary epithelium. Breast Cancer Res. 17(1):79. (* Co-senior authors)
Chew GL, Huo CW, Huang D, Blick T, Hill P, Cawson J, Frazer H, Southey MC, Hopper JL, Britt K, Henderson MA, Haviv I, Thompson EW (2014). Effects of tamoxifen and oestrogen on histology and radiographic density in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers. Breast Cancer Res Treat. 148(2):303-14.
Britt K, Short R (2012). The plight of nuns: the hazards of nulliparity. Lancet. 379(9834):2322-3.
Britt KL, Kendrick H, Regan JL, Molyneux G, Magnay FA, Ashworth A, Smalley MJ (2009). Pregnancy in the mature adult mouse does not alter the proportion of mammary epithelial stem/progenitor cells. Breast Cancer Res. 11(2):R20.
Genevieve V Dall, Samuel Hawthorne, Yashar Seyed-Razavi, Jessica Vieusseux, Wanfu Wu, Jan-Ake Gustafsson, Gail P Risbridger, Kara L Britt Estrogen receptor subtypes dictate the proliferative nature of the mammary gland, J Endocrinology, 2018, 237(3):323-336.
Cecilia W. Huo, Prue Hill, Grace Chew, Paul J Neeson, Heloise Halse, Elizabeth D. Williams, Michael A. Henderson, Erik W. Thompson# and Kara Britt # High mammographic density is associated with protumour inflammation, Breast Cancer Research, 2018: 20:92. # co-senior
Robin L. Anderson, Wendy V. Ingman and Kara L. Britt. Editorial: How reproductive History influences our Breast Cancer risk, Frontiers in Oncology, 2017, 7:289
Genevieve V Dall, Jessica L Vieusseux, Kenneth S Korach, Yukitomo Arao, Sylvia C Hewitt, Katherine J Hamilton, Elaine Dzierzak, Wah Chin Boon, Evan R Simpson, Robert G Ramsay, Robin L Anderson, Gail P Risbridger and Kara L Britt, Sca-1 delineates an estrogen responsive stem cell population within the mammary gland, Stem Cell Reports, 2017;8(2):417-431.
Genevieve V Dall and Kara L Britt, Estrogen Effects on the Mammary Gland in Early and Late Life and Breast Cancer Risk, Frontiers in Oncology 2017, doi: 10.3389/fonc.2017.00110
Cecilia W. Huo, Mark Waltham, Christine Khoo, Stephen Fox, Prue Hill, Shou Chen, Grace L Chew, John Price, Chau H. Nguyen, Elizabeth Williams, Michael Henderson, Erik W Thompson and Kara Britt. High mammographic density breast tissue stimulates ductal carcinoma in-situ progression to invasive lesions. Breast Cancer Research, 2016; 18:106
C. W. Huo, G. L. Chew, P. Hill, D. Huang, A. Vohora, W. V. Ingman, D. J. Glynn, M. A. Henderson, #E.W. Thompson and #K. L. Britt. Reconstitution of human mammary tissues in murine engineering chambers after collagenase digestion and flow cytometry isolation to single cells, Cell Biology International, 2016, Sep 3. doi: 10.1002/cbin.10675.
Honours and PhD projects are available.