I obtained my university degree in Microbial Biology and Genetics at the Faculty of Science, University of Lisbon, in 2004, after completing a Research Training in Pavia (Italy). My PhD was carried out in Bilbao (Spain) under the supervision of Dr Maria Vivanco, and was funded by a Portuguese FCT (Science and Technology Foundation) scholarship. My PhD studies were mainly focused on analysing the effects of estrogen in human breast stem cells. In 2011, I joined Dr Rob Clarke’s group, at the University of Manchester (UK), and since then I have been investigating the role that breast cancer stem cells play in the acquisition of endocrine therapy resistance in estrogen receptor-positive tumours. The ultimate goal of my work is to provide new insights into the biology of breast cancer that can be relevant to the clinical setting by improving treatments and contributing to a reduction in breast cancer mortality.
I have presented my work in several national and international conferences, including the Gordon Research Conference on Mammary Gland Biology and the American Association for Cancer Research (AACR) annual meeting. In 2016, I will serve as co-chair of the Gordon Research Seminar on Mammary Gland Biology in Italy.

New developments in endocrine therapy resistance in breast cancer

About 75% of breast cancers are (ER+) and are treated with endocrine therapies (e.g. tamoxifen) that disrupt the function of ER to prevent tumour growth. Although more than 50% of patients with ER+ tumours initially respond to endocrine therapies, nearly two-thirds of the patients do not benefit from these therapies, eventually recurring and succumbing to their disease. Consequently there is a need to understand why so many patients with ER+ breast cancer either fail to respond to endocrine therapies at diagnosis or develop resistance to these therapies.

We have reported that endocrine therapies like tamoxifen or fulvestrant do not target Cancer Stem Cells (CSCs), which may explain how residual drug-resistant cells are responsible for relapse of ER+ tumours following endocrine therapy.

Recently, we demonstrated that endocrine therapy resistance in human breast tumours is driven by JAGGED1-NOTCH4 signalling-dependent CSC activity (Simões et al., Cell Reports, 2015). Therapies inhibiting this CSC-associated pathway can be effective to target tumour CSCs that evade endocrine therapies. However, since CSCs may employ different signalling pathways we are currently investigating at single cell level the cellular heterogeneity among endocrine resistant CSCs.

In summary, I will discuss the role that breast CSCs play in the acquisition of endocrine resistance and show evidence that combining CSC pathways inhibitors together with endocrine therapies can potentially improve the treatment of patients with ER+ breast cancer.