Breast cancer is the most common malignancy among women in the Western World, accounting for almost 30% of the female cancers diagnosed in Sweden. Over 70% of breast cancers are ER+ and rely on this steroidal transcription factor to drive growth and survival. In spite of the advances made in adjuvant treatment to target ER, up to 20% of ER+ breast cancer patients relapse and, to date, metastatic breast cancer remains an incurable disease. Many clinical trials have proven that ER is a main driver of tumor progression also in the metastatic setting and the use of endocrine therapy, namely aromatase inhibitors (AIs) selective estrogen receptor modulators (SERMs) or selective estrogen receptor degraders (SERDs) such as fulvestrant, can effectively control the disease and induce tumor responses in a large proportion of patients. However, the majority of metastatic patients progress during therapy and eventually become resistant to endocrine treatment.
Accumulating evidences support the hypothesis that tumor progression is driven by a small subset of cancer stem cells with distinct molecular and functional characteristics. These cells may be derived from mutated normal stem or early progenitor cells. The quiescent state of normal as well as cancer stem cells, together with intrinsic mechanisms to prevent or repair DNA damage, makes them more resistant to conventional cancer therapy. The persistence and dormant state of cancer stem cells may be the cause of resistance to hormonal treatment and of the relapse in patients with ER positive breast cancer. Dormant cancer stem cells that will eventually generate recurrences may remain quiescent for a very long time, during which they can acquire features that will drive the relapse, especially under therapeutic pressure exerted by long adjuvant endocrine treatment.
Our ultimate research goal is to find improved ways to treat patients with metastatic breast cancer. By identifying the signaling pathways that are active in recurrent disease and studying responses to targeted therapies against such pathways, we hope to understand better the mechanisms of progression and treatment resistance. Particularly, we want to explore the involvement of the cancer stem cell population. To date there is no specific treatment that is demonstrated to target this cell population, but if the cancer stem cell population could be specifically and efficiently targeted, the tumor-driving cells would be depleted. Combining cancer stem cell targeted therapy with conventional treatments may represent a more efficacious treatment, resulting in better survival for breast cancer patients.