Establishment of Molecular Profiling for Individual Clinical Routine Treatment Decision in Early Breast Cancer

Several known prognostic factors are used to identify breast cancer patients with an unfavourable prognosis to receive adjuvant systemic therapy, such as tumor size, histological grade, hormone receptor status and axillary lymph node metastasis. However, a large majority of early stage breast cancer patients with small primary tumors and no lymph-node metastasis receive such treatment without being at risk of developing recurrent distant disease. Furthermore, today still only about 1/3-1/2 of the patients with occult residual cancer who receive standard adjuvant chemotherapy and/or endocrine therapy are cured as a consequence of this treatment.Therefore, the future clearly needs a more precise stratification for treatment decisions. As several alternative potent therapeutic agents exist for breast cancer, a detailed characterization of the individual breast cancer disease may improve individualized prognostication and treatment. The possibilities for detailed characterization of the primary tumor have grown substantially during the last 10 years, and the prognostic and predictive impact of various molecular-based analytical tests and algorithms has been established. In order to bring forward such strategies to the individual patient in a routine clinical setting, a project with a clear goal of establishing and evaluating the most validated molecular profiles is needed.This project will evaluate the consequences of a molecular based classification of breast cancer on treatment selection as well as on economical issues such as laboratory expenses and costs related to treatment. The safety and reproducibility of the molecular assays will also be evaluated and compared to existing prognostic and predictive markers. Finally, it will also provide an opportunity for development and prospective testing of novel prognostic or predictive subtype-specific molecular markers. The project is multidisciplinary involving personnel from the following disciplines; pathology, molecular pathology, surgery, oncology and molecular biology.

Patients with lymph node negative ER+positive HER2 negative breast cancer who have completed primary surgery, are candidates for this study. Patient can be included after written informed consent has been obtained and eligibility has been established and approved. It will be organized as a multi-center study. The study will be run as a one-armed trial. Patients with appropriate primary tumor characteristics will be informed at first postoperative visit.

Treatment recommendations will be based on the Prosigna test result, in addition to conventional clinicopathological parameters. The Prosigna test will be performed after study inclusion. Before the Prosigna test result will be informed, the treating physician has to report the type of adjuvant treatment that would have been recommended without performing the Prosigna test. After the Prosigna test results is available, the final decision of adjuvant systemic treatment plan is registered.

During and after adjuvant treatment, the follow-up of patients will be according to usual care and Norwegian Breast Cancer Group (NBCG) guideline recommendations, including annual mammography and/or breast ultrasound. The events recorded during follow-up will be reported in the Norwegian Breast Cancer Registry (NBCR) which will be the main study CRF. The annual follow-up can be organized at the hospital or with the general practioner (including telephone contact from study center).

The study will recruit a total of 2150 patients, of whom approximately 1500 will not be recommended chemotherapy. After inclusion, the patients will be followed for breast cancer related events for at least 5 years (8 years from study start).