It was determined that we had sufficient enrollment and study data to explore the impact of the Endopredict test in endocrine therapy decision-making.

The purpose of this study is to evaluate the impact of using EndoPredict® clinically to inform treatment decisions for extended endocrine therapy, and the subsequent impact on patient outcomes.

The EndoPredict® molecular test is validated to predict late distant recurrence after 5 years of endocrine therapy in women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) early stage breast cancer, with or without treatment with adjuvant chemotherapy. The test provides an individualized EPclin score based on the tumor gene expression, tumor size and nodal status, and categorizes patients as High or Low risk of distant recurrence.

The primary objective of this study is to evaluate the distant recurrence-free survival (DRFS) at 5-10 years in patients with ER+/HER2- early stage breast cancer with EPclin Low scores that did not extend endocrine therapy.

Data collection is prospective and patient enrollment is expected to occur over 24 months. The study will enroll patients who are near the 5-year post-diagnosis time point when decisions on extending endocrine therapy are being made. Patient breast cancer tumors, stored from surgical collection after initial diagnosis, will be tested with EndoPredict and a report generated. The provider will convey the report results to the patient and establish a treatment plan to continue or forgo endocrine therapy. Patients will then be followed for 6 years with data collection every year, and outcomes (distant and local disease recurrence, second primary breast cancer, etc.) recorded.

The associations between outcomes and treatment, EPclin score and risk category, EP molecular score, and clinicopathologic features will be investigated in all patients and in subpopulations (node negative, node positive, treated with or without chemotherapy, etc.).

Inclusion Criteria:

• Female
• At least 18 years of age at time of enrollment
• Able to provide informed consent
• ER+, HER2- breast tumor
• Stage T1-T3
• Currently receiving endocrine therapy
• Are between 4 and 6.5 years post-invasive breast cancer diagnosis
• Have all available information to produce an EPclin score, including treatment-naïve tumor stage, nodal status, and sufficient amount of remaining tissue from biopsy or resection to perform genomic testing (section 9)
• Patient and physician are willing to consider a change in endocrine therapy

Exclusion Criteria:

• Metastatic disease or currently active additional cancer diagnosis (except non- melanoma skin cancer) or any second primary breast cancer (includes ductal and/or lobular carcinoma in situ)
• Patient received systemic chemotherapy within 1 year of enrollment
• Currently enrolled in an interventional clinical trial or other clinical trial that precludes freely making decisions regarding extended endocrine therapy
• More than 3 positive nodes
• Received neo-adjuvant treatment (new-adjuvant chemotherapy or neo-adjuvant endocrine therapy)
• Are beyond 7 years post-breast cancer diagnosis

The primary objective of this study is to evaluate distant recurrence-free survival (DRFS) between years 5 and 10 post-diagnosis of women with ER+, HER2- breast cancer who are classified as low risk according to their EPclin score and who did not receive extended endocrine therapy.

Approximately 2,800 patients with ER+, HER2- breast cancer will be enrolled in this study across multiple sites. These patients will include both node-positive and node negative patients, with a minimum of 1673 patients with low-risk EPclin scores including 1,505 who forego extended endocrine therapy. Patients will be eligible for the study if they meet the following inclusion criteria.