A study of the effect of adding anti-hormone therapy to so-called PARP inhibitor therapy in patients with advanced and metastatic hormone receptor-positive breast cancer.

Breast cancer (mammary carcinoma) is a malignant disease of the mammary gland tissue characterized by the uncontrolled proliferation of mammary gland cells. Treatment of the disease depends on numerous factors, such as the patient’s overall health, the stage (extent) of the disease, the tumor’s growth rate (Ki-67 index), the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased presence of the HER2 receptor on the cells (HER2-positive). In a locally advanced stage (Stage 3) or when metastases have already been detected in the body, the disease is often no longer curable. Hereditary factors can increase the risk of breast cancer. A significant genetic change is a mutation in the BRCA1 or BRCA2 gene, which substantially increases the lifetime risk of breast and ovarian cancer.

Hormone receptor-positive breast cancer is usually treated with anti-hormone therapy. Various classes of medications are used for this purpose: aromatase inhibitors (e.g., letrozole), drugs that degrade the estrogen receptor (SERDs, e.g., elacestrant or fulvestrant), or drugs that modulate the receptor (SERMs, e.g., tamoxifen). If the disease progresses despite anti-hormone therapy, the cancer cells have often developed resistance mechanisms. Studies show that PARP inhibitors such as olaparib can prevent disease progression in patients with BRCA1/2 mutations. Olaparib is already approved.

The goal of the ELEMENT trial is to determine whether a combination of olaparib and elacestrant is superior to olaparib alone. Elacestrant is already approved for hormone receptor-positive breast cancer in the advanced or metastatic stage following failure of anti-hormone therapy. It belongs to the SERD class and is taken orally.

Patients will be randomly assigned to two study arms in a 2:1 ratio. The experimental arm will receive olaparib plus elacestrant, while the control arm will receive olaparib alone. Treatment continues until disease progression or until the end of the study, for a maximum of 48 months. The study is open-label, meaning that both medical staff and patients know which study arm they are in.

Eligible participants include women and men aged 18 and older with hormone receptor-positive, HER2-negative breast cancer at the locally advanced (Stage 3) or metastatic (Stage 4) stage, in whom a BRCA1/2 mutation has been detected. Participants must have already undergone chemotherapy and an initial course of anti-hormone therapy, during which disease progression was documented. Prior treatment with PARP inhibitors is not permitted. Metastases must not be actively present in the brain and must not cause debilitating symptoms in other organs.