Elacestrant for Treating ER+/HER2- Breast Cancer Patients With ctDNA Relapse (TREAT ctDNA)

Inclusion Criteria

• •1. ctDNA screening phase:
• •• Female (both pre- and postmenopausal) or male patients with histologically confirmed ER positive (regardless of PR),
• •HER2 negative breast cancer, according to local pathologist:
• •* ER-positive defined as ≥ 10% of cells staining positive for ER or Allred proportion score ≥3
• •* HER2-negative defined as a score of 0, 1+ by immunohistochemistry (IHC) or a negative in situ hybridization (ISH) based on single-probe average HER2 copy number, as per American Society of Clinical Oncology guidelines
• •* Intermediate to high risk of recurrence after definitive treatment for early breast cancer, defined as:
• •FOR PATIENTS TREATED WITH PRIMARY SURGERY:
• •* Any patient with ≥ 4 positive axillary lymph nodes (stage pN2-3).
• •* 1-3 positive axillary lymph nodes (stage pN1) and either:
• •* Tumour size ≥ 5 cm or/and
• •* Histologic grade 3 or/and
• •* Ki67≥20% or/and
• •* High genomic risk defined as Oncotype Dx Recurrence Score \>=26, Mammaprint high risk, Prosigna score \>40 or EPclin risk score \>=4.0.
• •* Negative axillary lymph nodes (stage pN0) and tumour size ≥ 5 cm and either
• •* Histologic grade 3 a or/and
• •* Ki67≥20% and/or
• •* High genomic risk defined as Oncotype Dx Recurrence Score \>=26, Mammaprint high risk, Prosigna score \>60 or EPclin risk score \>=4.0. FOR PATIENTS TREATED WITH NEOADJUVANT
• •SYSTEMIC TREATMENT FOLLOWED BY SURGERY:
• •* Patient may have received neoadjuvant endocrine therapy or neoadjuvant chemotherapy provided that:
• •* The initial tumour and/or the tumour after surgery meet the criteria above defined for patients treated with primary surgery or the initial tumour was staged as cT4anyN and
• •* There is no pathological complete response, defined as no invasive disease in the breast and axilla (ypT0/is ypN0).
• •* Age ≥18 years
• •* Patients must have received at least 1 year and up to 7.5 years of ET and planned to continue adjuvant ET during ctDNA screening phase
• •* Previous adjuvant CDK4/6 inhibitor or PARP-inhibitor treatment is allowed provided it is completed
• •* Invasive multicentric / multifocal disease is allowed provided that all the tested foci are ER+ HER2-. A sample from the highest-risk one, according to the investigator decision based on the size and grade, should be sent to Natera to build the patient ctDNA assay.
• •* Available tumour sample from resected or biopsied tissue, with a tumour content of ≥20% (30% preferred) either before or after macro dissection (if performed) and a cell viability of a minimum 100 cells.
• •* Core Needle Biopsies (CNB): recommended minimum of four (4) cores per block
• •* Fine Needle Aspirates (FNA) are not accepted
• •* The following sample types are acceptable:
• •* 6-10 unstained slides (charged and unbaked) of 10μm each (or 12-19 unstained slides at 5 μm each), PLUS one contiguous H\&E slide. Minimum total tissue thickness must be 60μm OR
• •* FFPE tissue block with 25mm2 minimum surface area
• •* Written informed consent must be given according to ICH/GCP, and national/local regulations.
• •ctDNA positive according to the Signatera ctDNA assay (main study ctDNA test) or other ctDNA assay approved for diagnostic purposes.
• •Patients must meet the eligibility criteria for the screening phase, with the exception of the tissue sample requirements.
• •Patients must receive adjuvant ET at the time of the ctDNA positive test
• •Absence of locoregional and/or metastatic disease and/or new malignancy, as investigated by:
• •Mammogram (unilateral in case of mastectomy; not required in patients having undergone bilateral mastectomy) NOTE: if local investigator plans to use MRIs instead of mammograms during the study, MRI will have to be performed at baseline.
• •CT thorax and abdomen/pelvis with IV contrast. In case of any contra-indications (medical or regulatory): CT thorax without contrast + MRI abdomen/pelvis.
• •Technetium-99m bone scintigraphy
• •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• •Adequate organ function
• •Women of childbearing potential (WOCBP) must have a negative highly sensitive serum or urine pregnancy test within 7 days prior to randomisation.