Duration: 36 months
Small or medium-scale
focused research project
5 million euro
HEALTH.2013-0-1: Boosting the translation of health research projects results into innovative applications for health
About breast cancer
Breast cancer is the most common malignancy among women in the Western World. Although the majority present with localized disease and can be cured, around 25% of patients will develop incurable metastatic disease. Besides, approximately 3-10% of all patients with breast cancer have distant metastases at initial presentation.1 Patients with metastatic disease are treated with systemic therapies aiming to prolong life while maintaining an acceptable quality of life. As the use of systemic anti-tumor agents is always accompanied by unwanted side-effects, one of the major challenges of today’s oncology is to personalize medicine, i.e. adapting therapy to characteristics of individual patients and tumors in order to maximize treatment response and minimize toxicity. Consequently, there is a high need for predictive factors to guide treatment.
Two of the most intensively investigated predictive factors and the only factors used for tailoring of breast cancer treatments in current clinical practice are the estrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2). Overexpression of ER occurs in 60-70% of patients and forms a target for hormonal therapies, such as aromatase inhibitors. Its predictive value for response to endocrine treatment is well-documented.2 In 15% of breast cancers HER2 is overexpressed, which is predictive for response to anti-HER2 agents, such as trastuzumab and lapatinib. However, since it is increasingly acknowledged that characteristics of the metastases can differ from the primary tumor, taking biopsies from metastatic sites at time of start treatment for metastatic disease is becoming part of standard care. Studies have shown that in approximately 10% of patients with originally HER2-negative breast cancer, the metastases are positive for HER2, suggesting that these patients might benefit from the trastuzumab they are not allocated to based on the characteristics of the primary tumor.3 For ER, up to 30% of patients might incorrectly receive hormonal treatments when the expression of ER is lost on the metastases.3
Even though it might have clinical implications, clinicians frequently refrain from taking biopsies, given the invasiveness of the procedure and the risk for complications. Therefore, CTCs might provide a more patient-friendly method, and on top of that allow for repetitive analysis throughout treatment. The aim of the CareMore project is to develop a clinically validated characterization method for CTCs and this way greatly aids to a more personalized breast cancer approach that will ultimately lead to improved survival for patients with metastatic breast cancer.
1. Ruiterkamp J, Ernst MF, de Munck L, van der Heiden-van der Loo M, Bastiaannet E, van de Poll-Franse LV, Bosscha K, Tjan-Heijnen VC, Voogd AC. Improved survival of patients with primary distant metastatic breast cancer in the period of 1995-2008. A nationwide population-based study in the Netherlands. Breast Cancer Res Treat 2011;128:495-503.
2. Early Breast Cancer Trialists' Collaborative G. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-717.
3. Lindstrom LS, Karlsson E, Wilking UM, Johansson U, Hartman J, Lidbrink EK, Hatschek T, Skoog L, Bergh J. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol 2012;30:2601-8.