IMaging PAtients for Cancer Drug selecTion - Metastatic Breast Cancer

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.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Patient with first presentation of MBC, regardless of ER and HER2 status of the primary tumor, who is eligible for first-line systemic therapy.
* Patient with non-rapidly progressive MBC, not requiring urgent initiation of chemotherapy, based on clinician's evaluation which may include:

  * no recent (\< 2 weeks prior to screening visit) significant worsening of MBC related signs and symptoms according to patient history.
  * in case of liver metastases: no significant increase in liver function tests alanine aminotransferase aspartate transaminase (ASAT) and alanine transaminase (ALAT) in 2 weeks prior to screening visit. (Significant increase of liver function test is defined as 50% increase of absolute amount of ASAT/ALAT.)
* Patients in whom standard imaging work-up of MBC was recently (≤ 28 days) performed. Standard imaging must include: CT chest/abdomen, 18F-FDG-PET and bone scintigraphy.
* Patient with measurable or clinically evaluable (bone only) disease on recent standard work up of MBC are eligible.
* Metastatic lesion(s) of which a histological biopsy can safely be obtained according to standard clinical care procedures.
* Primary tumor blocks available for confirmatory central laboratory ER/HER2 testing in the UMCG. If available a snap frozen sample of the primary tumor will also be centralized in the University Medical Center Groningen (UMCG).
* WHO performance status 0-2.
* Patient is able to undergo PET imaging procedures.
* Age \>18 years of age, willing and able to comply with the protocol as judged by the investigator.
* Signed written informed consent.

Exclusion Criteria:

* Contraindications for systemic treatment (as will be assigned based on biopsy and experimental scan results), either chemotherapy, hormonal therapy or anti-HER2 therapy, based on clinical judgment of treating medical oncologist and patient history.
* Pregnant or lactating women.
* Prior allergic reaction to immunoglobulins or immunoglobulin allergy.
* Inability to comply with study procedures.
* Rapidly progressive (visceral) disease requiring rapid initiation of chemotherapy.

• DERIVEDvan Geel JJL, Eisses B, Elias SG, Brouwers AH, Bensch F, Gerritse SL, Angus L, Glaudemans AWJM, Kuip EJM, Jager A, Oprea-Lager DE, Vugts DJ, Emmering J, Arens AIJ, Oyen WJG, van der Vegt B, Lub-de Hooge MN, Menke-van der Houven van Oord CW, de Vries EGE, Schroder CP; IMPACT-Metastatic Breast Cancer Consortium. 18F-Fluorodeoxyglucose Positron Emission Tomography for Estimating Outcomes After Initial Treatment for Metastatic Breast Cancer: A Nonrandomized Clinical Cohort Trial. JAMA Oncol. 2026 Jun 1;12(6):611-618. doi: 10.1001/jamaoncol.2026.0767. PMID 41989806
• DERIVEDvan Geel JJL, Moustaquim J, Boers J, Elias SG, Smeets EMM, Knip JJ, Glaudemans AWJM, de Vries EFJ, Hospers GAP, van Kruchten M, Stokkel M, Oprea-Lager DE, Menke-van der Houven van Oordt WC, de Vries EGE, Schroder CP; IMPACT-Metastatic Breast Consortium. Intrapatient 16alpha-[18F]Fluoro-17beta-Estradiol PET Heterogeneity as a Prognostic Factor for Endocrine Therapy Response and Survival in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer. J Nucl Med. 2025 Feb 3;66(2):194-200. doi: 10.2967/jnumed.124.268984. PMID 39848768
• DERIVEDBoers J, Eisses B, Zwager MC, van Geel JJL, Bensch F, de Vries EFJ, Hospers GAP, Glaudemans AWJM, Brouwers AH, den Dekker MAM, Elias SG, Kuip EJM, van Herpen CML, Jager A, van der Veldt AAM, Oprea-Lager DE, de Vries EGE, van der Vegt B, Menke-van der Houven van Oordt WC, Schroder CP; IMPACT-Metastatic Breast Consortium. Correlation between Histopathological Prognostic Tumor Characteristics and [18F]FDG Uptake in Corresponding Metastases in Newly Diagnosed Metastatic Breast Cancer. Diagnostics (Basel). 2024 Feb 14;14(4):416. doi: 10.3390/diagnostics14040416. PMID 38396455
• DERIVEDvan Geel JJL, Boers J, Elias SG, Glaudemans AWJM, de Vries EFJ, Hospers GAP, van Kruchten M, Kuip EJM, Jager A, Menke-van der Houven van Oordt WC, van der Vegt B, de Vries EGE, Schroder CP; IMPACT-Metastatic Breast Consortium. Clinical Validity of 16alpha-[18F]Fluoro-17beta-Estradiol Positron Emission Tomography/Computed Tomography to Assess Estrogen Receptor Status in Newly Diagnosed Metastatic Breast Cancer. J Clin Oncol. 2022 Nov 1;40(31):3642-3652. doi: 10.1200/JCO.22.00400. Epub 2022 May 18. PMID 35584346