Knowledge of breast cancer estrogen receptor (ER) expression is of major importance in treatment-decision making. Patients with ER-positive tumors can be treated with anti-oestrogen therapy, which has relatively few side effects compared to chemotherapy. Whole-body tumor ER-expression can be visualized by 18F-fluoroestradiol PET imaging (FES-PET). In addition to ER, the androgen receptor (AR) is a potential new target in breast cancer. PET imaging with 18F-fluorodihydrotestosterone (18F-FDHT) may allow visualization of tumor AR-expression. In the current study we will perform FES-PET and FDHT-PET in metastatic breast cancer patients and evaluate the concordance with concurrent biopsies. Molecular imaging of tumor AR- and ER-expression may well be of value for future treatment decision-making.

Inclusion Criteria:

1. Metastatic breast cancer, with at least one known metastasis outside of the liver

2. Presence of a lesion that is safely accessible for tumor biopsy (may be liver lesion)

3. Postmenopausal status defined as one of the following:

   • age ≥60 years
   • previous bilateral oophorectomy
   • age <60 years and amenorrhea for >12 months in the absence of interfering hormonal therapies (such as LH-RH agonists and ER-antagonists)
   • patients age <60 years using an ER-antagonist should have amenorrhea for > 12 months and FSH >24 U/L and LH >14 U/L e. patient age <60 years using LH-RH agonists should continue LH-RH-agonists until after the PET procedures

4. Initially ER-positive tumor histology.

5. ECOG performance status 0-2.

6. Signed written informed consent

7. Able to comply with the protocol

Exclusion Criteria:

1. Use of estrogen receptor ligands, including tamoxifen, fulvestrant or estrogens, or androgen receptor ligands, during the 6 weeks before entry into the study
2. Life-expectancy ≤ 3 months