COntinue the SaMe Systemic Therapy After Local Ablative Therapy for Oligo Progression in Metastatic Breast Cancer - the COSMO Study

Inclusion Criteria:

• Histologically confirmed invasive breast cancer

• Metastatic breast cancer

• Oligoprogression defined as one or two distant metastatic lesions, limited to oneorgan, or the primary tumor or locoregional lymph nodes, increasing ≥20% in size andbe larger than 15 mm or if metabolic activity increases (with 20% in SUVmax) onFDG-PET-CT.

• Systemic treatment can be either endocrine, targeted, chemotherapy orimmune-checkpoint blockade

• Patients should be on systemic therapy for at least six months. Status should bestable disease or partial or complete response for at least 6 months.

• Oligoprogression has to be detected with radiological imaging comparing the lesionon the same type of imaging modality as has been used at the start of systemictherapy.

• The radiological imaging that shows progression must be performed within 70daysprior to LAT.

• Bone metastases are classified as progressive if the lytic component of the lesionincreases by ≥20% or the FDG-uptake increases by ≥20% on FDG-PET-CT

• Oligo-progression has to be confirmed with a FDG-PET-CT-scan 5-7 weeks after theinitial scan that showed oligoprogression.

• Lesion(s) must be amenable to resection, radiotherapy or radiofrequency ablationwith the intent of local obliteration

• Age ≥18

• World Health Organization (WHO) Performance Status 0 or 1

• Signed written informed consent before patient registration according to ICH/GCP,and national/local regulations

Exclusion Criteria:

• Having received more than two lines of systemic therapy for MBC If a treatmentregimen has been de-escalated without adding other therapies, this is seen as oneline of therapy. For example: Pertuzumab/trastuzumab+docetaxel followed bypertuzumab/trastuzumab will be viewed as one line of systemic therapy.

• Other malignancy except carcinoma in situ and basal-cell and squamous cell carcinomaof the skin, unless the other malignancy was treated ≥5 years ago with curativeintent without the use of chemotherapy or radiation therapy

• Current pregnancy or breastfeeding. Women of childbearing potential must useadequate contraceptive protection

• Presence of any medical condition that would place the patient at unusual risk, upto the discretion of the clinician

• Presence of any psychological, familial, sociological, or geographical conditionpotentially hampering compliance with the study protocol and follow-up schedule