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.
A mouse model of endocrine therapy for pre-clinical testing of breast cancer preventatives
Tamoxifen inhibits the growth of breast cancer and is an approved preventative for high risk women. However, Tamoxifen has poor uptake rates and adherence due to perceived and real side effects. As our lab identifies new preventatives to be tested in our pre-clinical in-vivo models, we will trial these against Tamoxifen, the “current standard of practice” for women. This project will involve developing a robust a mouse model of endocrine therapy for use in in-vivo pre-clinical testing of novel breast cancer preventatives.
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.
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, Vieusseux J, Seyed-Razavi Y, Godde N, Ludford-Menting M, Russell SM, Ashworth A, Anderson RL, Risbridger GP, Shackleton M, Britt KL, Parity reduces mammary repopulating activity but does not affect mammary stem cells defined as CD24 + CD29/CD49fhi in mice. Breast Cancer Res Treat. 2020 Oct;183(3):565-575.
Britt KL*, Cuzick J, Phillips KA, Key steps for effective breast cancer prevention. Nat Rev Cancer. 2020 Aug;20(8):417-436. (*corresponding author)
Tower H, Ruppert M, Britt K, The Immune Microenvironment of Breast Cancer Progression. Cancers (Basel). 2019 Sep 16;11(9):1375.
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, Hawthorne S, Seyed-Razavi Y, Vieusseux J, Wu W, Gustafsson JA, Byrne D, 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.
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 G, Risbridger G, Britt K, Mammary stem cells and parity-induced breast cancer protection- new insights. J Steroid Biochem Mol Biol. 2017 Jun;170:54-60.
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.
Anderson RL, Ingman WV, Britt KL, Editorial: How Reproductive History Influences Our Breast Cancer Risk. Front Oncol. 2017 Dec 4;7:289.
Unsworth A, Anderson R, Haynes N, Britt K, Two multi-color immunophenotyping panels for assessing the innate and adaptive immune cells in the mouse mammary gland. Cytometry A. 2016 Jun;89(6):527-30.
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. 2015 Jun 4;17(1):79. (* Co-senior authors)
Dall G, Vieusseux J, Unsworth A, Anderson R, Britt K, Low dose, low cost estradiol pellets can support MCF-7 tumour growth in nude mice without bladder symptoms. J Cancer. 2015 Oct 29;6(12):1331-6.
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, 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. 2014 Nov;148(2):303-14.
Britt K, Short R. The plight of nuns: the hazards of nulliparity. Lancet. 2012 Jun 23;379(9834):2322-3.
Britt KL, Kendrick H, Regan JL, Molyneux G, Magnay FA, Ashworth A, Smalley MJ, Pregnancy in the mature adult mouse does not alter the proportion of mammary epithelial stem/progenitor cells. Breast Cancer Res. 2009;11(2):R20.
Honours and PhD projects are available.