IMaging PAtients for Cancer Drug selecTion - Metastatic Breast Cancer

Overview

Current patient work-up, including conventional imaging and pathological assessment of just one single biopsy, might be insufficient to identify metastatic breast cancer patients, who possibly benefit from first-line anti-hormonal or anti-HER2 therapy. As receptor conversion of the tumor is found quite frequently and molecular heterogeneity can occur within one patient, up-to-date whole body information is necessary to determine estrogen receptor (ER) and/or human epidermal growth factor receptor 2 (HER2) receptor status and subsequently guide therapy decision. With molecular imaging via PET this information can be obtained in a non-invasive, patient friendly way. Furthermore, to improve and individualize treatment and be able to identify (new) drug targets and biomarkers, sampling of venous blood, circulating tumor cells (CTC), as well as circulating tumor DNA, microRNA (miRNA) and molecular characterization of one metastasis at the beginning and, if feasible, of an additional biopsy during therapy, is necessary.

Patient selection for hormone therapy and anti-HER2 therapy is based on the presence of their respective targets, the ER and HER2, as currently assessed on tumor tissue by molecular biological techniques. In primary breast cancer, both ER and HER2 are powerful predictors for response to ER or HER2 targeting treatment, driving treatment decisions. If both receptors are absent, targeted hormone or anti-HER2 therapy will not be administered and chemotherapy is the only therapeutic option left. MBC management in oncology practice is often based on ER and HER2 status of the primary tumor. However, a biopsy of a metastasis is considered part of the standard work up for MBC, in view of the potential conversion of ER and HER2 during the course of the disease. In contrast to primary breast cancer, no prospective studies have been done to evaluate the impact of (converted) receptor status on metastases, on prognosis and prediction of response to subsequent targeted therapy. Although receptor conversion in MBC is a well known phenomenon, clinicians may refrain from having a biopsy taken, for instance when it would require a highly invasive procedure. Even if it is feasible, the biopsy will only reflect ER and HER2 status of a single lesion, and disregard the potential heterogeneity of expression of ER and HER2 status between and within metastatic lesions. Therefore, the current standard work up of MBC is not adequate enough or too invasive in a relevant proportion of MBC patients to drive treatment decisions. As a result, these patients incorrectly receive an ineffective treatment with potentially toxic effects. Meanwhile, an effective treatment for these patients may be delayed or even denied (such as chemotherapy or anti-HER2 based therapy) because of inadequate assessment of ER and HER2 status. This shows the need of obtaining up-to-date whole body information with information of characteristics of the different metastases within a patient. Non-invasive 18F-fluoroestradiol(18F-FES)-PET and Zirconium-89(89Zr)-trastuzumab-PET scan techniques are able to visualize the ER and HER2 in metastatic lesions throughout the whole body, and may therefore - in a patient friendly way- provide comprehensive information (i.e. of the primary tumor and various metastatic lesions) on ER and HER2 status. Furthermore, optimal selection of the right treatment for the right patient may not only reduce unnecessary toxicity, but also health care costs. Although various studies have already indicated the clinical utility of 18F-FES-PET and 89Zr-trastuzumab-PET, no prospective data are yet available assessing their predictive value (14-19). Therefore, it is clear that these new techniques, and also the aspects of cost-effectiveness, need to be prospectively evaluated within the framework of established assessments (including metastases biopsies and FDG-PET), to ensure their implementation in standard care.