Observational Study of Elacestrant Treatment in Patients with ESR1-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer

In hormone receptor-positive, HER2-negative breast cancer, the cancer cells have binding sites (receptors) for the hormone estrogen, which can stimulate tumor growth. At the same time, the tumor cells do not express elevated levels of the HER2 receptor, a protein on the cell surface that can also transmit growth signals into the cell. In the locally advanced or metastatic stage, this form of breast cancer is often initially treated with anti-hormone therapy, usually in combination with a CDK4/6 inhibitor. Over time, however, the disease may continue to progress despite this treatment. One possible cause of this is changes in the ESR1 gene. This gene contains the blueprint for the estrogen receptor alpha. If an ESR1 mutation is present, the estrogen receptor can remain permanently active even without the hormone estrogen. This is considered a major reason why existing anti-hormone therapy may eventually become ineffective (endocrine resistance). Elacestrant belongs to the class of selective estrogen receptor degraders (SERDs). These drugs bind to the estrogen receptor and cause its degradation within the cancer cell. Elacestrant is approved in the EU for the treatment of hormone receptor-positive, HER2-negative, locally advanced, or metastatic breast cancer with an ESR1 mutation, provided the disease has progressed following anti-hormonal therapy, including a CDK4/6 inhibitor.

The aim of this non-interventional observational study is to determine, in real-world clinical practice, how frequently a change in the ESR1 gene (ESR1 mutation) occurs following anti-hormonal therapy and what the effects of subsequent treatment with elacestrant are. There is no randomization and no blinding (open-label study). This means that both the patients and the study physicians know which treatment is being administered. Two groups are being observed: patients with an ESR1 mutation in the tumor, who are treated with elacestrant in accordance with the prescribing information, and patients with wild-type ESR1 (no evidence of an ESR1 mutation), who receive a standard treatment selected by the study physicians. The study will assess the incidence of the ESR1 mutation following anti-hormone therapy, quality of life, tolerability and safety, as well as the management of side effects.

Eligible participants are postmenopausal women aged 18 years or older with locally advanced and/or metastatic, hormone receptor-positive, and HER2-negative breast cancer whose disease has progressed following initial anti-hormonal therapy with a CDK4/6 inhibitor. Previous chemotherapy in the advanced or metastatic stage, as well as any contraindications to treatment with elacestrant as listed in the prescribing information, exclude participants from the study.