Breast Cancer with a BRCA Mutation: Study on a New Drug Combination Before Surgery

In the early stages, breast cancer is often treated with neoadjuvant therapy to shrink the tumor. This improves the chances of completely removing the tumor through surgery—which is crucial for a good prognosis. Breast cancer is generally classified into different subgroups based on specific characteristics of the tumor. For the OlympiaN study, in addition to being “early-stage,” the tumor must also be HER2-negative and have a BRCA mutation. The estrogen receptor (ER) must either be undetectable (negative) or only very weakly expressed (low). Treatment with olaparib is routinely administered for breast cancer that has already been treated surgically; olaparib inhibits tumor growth. Durvalumab is an antibody that interacts with the immune system to destroy tumor cells. It is already approved for lung cancer. This means that durvalumab is already in use, and data on the drug’s safety are available. However, it is not yet approved for breast cancer.

The goal of the OlympiaN study is to test olaparib as a neoadjuvant therapy (before surgery) and to compare which treatment is more effective: olaparib as monotherapy or the combination of olaparib and durvalumab. There are therefore two study arms, and patients will receive either olaparib alone or a combination of olaparib and durvalumab. Assignment to one of the two study arms (olaparib or olaparib + durvalumab) is based on whether the tumor is classified as low-risk (stage T1b-c/N0, Study Arm A) or as high-risk (Stage T2/N0 or T1/N1, Study Arm B). The study is therefore open-label, meaning that patients and medical staff know which study arm they are in. Treatment consists of 4–6 cycles, each lasting 28 days; the exact number of cycles will be determined by the medical staff. Afterward, the study treatment ends, and breast surgery is performed. A tissue examination (histology) is conducted to determine whether all tumor cells have been destroyed. This allows for a comparison of the effectiveness of both treatment approaches. Afterward, you will receive standard-of-care treatment, although treatment with olaparib may be continued if both doctors and patients deem it appropriate (not part of the study). Follow-up within the study lasts for up to 3 years.

Women and men aged 18 and older with early-stage breast cancer are eligible to participate in the study. The cancer must be operable and must not have metastasized. It must be HER2-negative, ER-negative, or ER-low, and must have a BRCA1 or BRCA2 mutation. The breast cancer must not have been previously treated.