CareMore study 1: prognostic value of HER2-positive circulating tumor cells in metastatic breast cancer patients treated with aromatase inhibitors (CareMore-AI study)

Treatment of metastatic breast cancer patients with hormonal agents is often
employed in the clinic. A worse outcome to hormonal therapy was observed in
patients with primary tumors expressing both ER and HER2 compared to patients
with primary tumors positive for ER but negative for HER2. Metastatic breast
cancer patients are still treated based on primary tumor characteristics, while
it is now increasingly appreciated that important characteristics like ER and
HER2 expression may differ between the primary tumor and the metastatic lesion.
Circulating tumor cells (CTCs) are cancer cells present in the peripheral blood
of patients with metastatic breast cancer and are thought to represent
characteristics of the metastases. We hypothesize that HER2 status on CTCs will
be stronger associated with outcome to hormonal therapy than HER2 status in
primary tumors. If so, this means that patients with primary tumors expressing
ER and lacking HER2, but with CTCs expressing HER2, should not be treated with
hormonal agents.

The primary objective is to determine the impact of HER2 expression in CTCs
taken at baseline on outcome to AIs in metastatic breast cancer patients with
an ER-positive primary tumor. Secondary objectives are to determine impact of
HER2 expression in CTCs taken at baseline on outcome to AIs combined with
CDK4/6 inhibitors. In addition, we will investigate genomic heterogeneity
within a patient on single CTC level.

Patients with metastatic breast cancer, with a HER2-negative and ER-positive
primary tumor and who are candidate to receive first-line aromatase inhibitor
treatment, will be included in this prospective, open study. In all patients,
50 mL of blood will be drawn at baseline for CTC CellSearch enumeration and CTC
characterization (as described in chapter 8.3). Following the start of AI
treatment, patient progression will be monitored for 6 months.

Based on the patients* CTC count and the emergence of HER2-positive CTCs (as
evaluated with the CellSearch method, see chapter 8.3.1), patients can be
divided into three groups:
1. CTC*s detectable, of which a subset is HER2-positive
2. CTC*s detectable, of which all are HER2-negative
3. No CTC*s detectable


When 6 months have passed since the inclusion of the last patient and the data
have been validated, the final analysis will be performed.

In all patients, 50 mL blood for CTC enumeration and CTC characterization will
be drawn at baseline during another blood draw that is already required for
standard care. Therefore, no risks are associated with participation in this
study.