Comparison of Treatments for Hormone-Receptor-Positive Premenopausal Breast Cancer

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue characterized by the uncontrolled proliferation of breast cells. Treatment occurs in several phases and depends largely on how widespread the tumor is (stages 1–4). For operable breast cancer, the standard of care is an initial phase of chemotherapy (neoadjuvant). This is followed by surgery on the breast and, if necessary, the lymph nodes, before further treatment (adjuvant) is administered, depending on individual factors. An important factor in selecting the medications for treatment is the characteristics of the cancer cells in the initial tissue sample. This includes, above all, whether hormone receptors are detectable on the surface of the cancer cells and the increased presence of the HER2 receptor. Both the hormones estrogen and progesterone, as well as HER2, can promote tumor growth. This study is testing anti-hormone therapy. To block the influence of estrogen on tumor growth, a combination of hormone blockers such as anastrozole and medications that inhibit estrogen production in the ovaries (such as triptorelin) is often used. This combination is therefore the standard of care for premenopausal women. The drug giredestrant is also used for anti-hormone therapy and belongs to the group of selective estrogen receptor degraders (SERDs), which promote the breakdown of estrogen receptors and thus inhibit estrogen-dependent tumor growth.

The goal of the PREcoopERA study is to investigate whether giredestrant, either alone or in combination with triptorelin, is as effective as—or even more effective than—the standard therapy with anastrozole and triptorelin.

Patients will be randomly assigned to three groups, each of which will receive their treatment for four weeks prior to the first phase of therapy (neoadjuvant chemotherapy). All participants are aware of their assignment (open-label). Study arm A receives giredestrant daily in tablet form until the day of surgery or repeat biopsy. The second group (arm B) is treated with giredestrant plus triptorelin; giredestrant is taken daily, and triptorelin is administered as a single injection on the first day of the study. Study arm C serves as the active control group receiving the current standard of care. Patients in this group receive anastrozole orally once daily and a single injection of triptorelin.

The study is a so-called “window-of-opportunity” study, which means that treatment is administered shortly before the actual standard therapy begins in order to evaluate the direct effect of the medications on the tumor. The primary objective of such a study is to assess how effectively the new drug or therapy affects the tumor without delaying or compromising the subsequent standard treatment. It is therefore not a complete course of treatment, but rather a targeted test to determine whether this therapy can effectively slow tumor growth. The Ki-67 index is used for this purpose. The Ki-67 index is a marker for the rate of cell growth. In this study, it is measured four weeks after the start of the study and compared with the value before the start of therapy. This is intended to evaluate and compare the growth-inhibiting effect of the medications.

Eligible participants are premenopausal adult women diagnosed with operable breast cancer. They must not have advanced (Stage 4) or inflammatory breast cancer. The breast cancer must be estrogen receptor-positive and HER2-negative and have a Ki-67 index greater than 10%.