LCD L37264: MolDX: EndoPredict Breast Cancer Gene Expression Test

This Medicare contractor will provide limited coverage for the EndoPredict ® breast cancer gene expression test (Myriad Genetic Laboratories Inc., Salt Lake City, UT) for the management of post-menopausal women diagnosed with early-stage (TNM stage T1-3, N0-1) estrogen-receptor (ER) positive, Her2-negative breast cancer, who are either lymph node-negative or who have 1-3 positive nodes, and for whom treatment with adjuvant endocrine therapy (e.g., tamoxifen or aromatase inhibitors) is being considered. The test is used by physicians in the management of these patients by identifying those who have sufficiently low risk of distant recurrence (DR) at 10 years and may safely forego chemotherapy.

In 2016, approximately 247,000 cases of breast cancer were diagnosed in the United States. 1 Approximately 75% of early-stage breast cancers are estrogen receptor (ER)-positive and HER2-negative, leading to treatment with adjuvant endocrine therapy (e.g., tamoxifen or aromatase inhibitors) that significantly improves prognosis. 2,3 Determining which patients with ER+/Her2- breast cancer will have a low enough risk of DR after 5 years of endocrine therapy to forgo adjuvant chemotherapy is a priority for physicians who manage these patients.

A 2012 meta-analysis by the Early Breast Cancer Trialist’s Collaborative Group demonstrated that all clinical risk groups of patients with early breast cancer experience a ~30% benefit from chemotherapy, in terms of decrease in DR rate. 4 Therefore, patients with a low underlying risk of DR will have a lower absolute benefit from chemotherapy, compared to patients with a high underlying risk of DR. For each patient, the expected absolute benefit of chemotherapy needs to be weighed against the 2-3% chance of treatment-related toxicity and long-term side effects.

Tumor size, grade, and nodal status are currently used for assessment of a patient’s distant recurrence risk to make decisions about the addition of chemotherapy to endocrine therapy. However, molecular tests have been shown to improve prognostic accuracy compared to standard clinical features and have become increasingly important for patients with ER+/Her2- breast cancer. These assays have become standard of care in the treatment of early stage breast cancer, to identify patients who have a low risk of DR such that chemotherapy would not provide an overall benefit, to directly predict chemotherapy benefit, and to help curtail costly overtreatment.

In determining the cutoff to identify low risk patients, breast cancer prognostic tests commonly use a threshold of a 10% risk of DR at 10 years. Patients with a risk under 10% are categorized as low risk. This 10% cutoff is a well-accepted standard used by many currently available breast prognostic tests and accepted by the American Society of Clinical Oncology (ASCO). 5 In addition, while hormone receptor-positive early-stage breast cancer patients have a favorable prognosis overall, there is an ongoing risk of distant recurrence (DR) and death. 15,16 Women with node-negative disease who received 5 years of endocrine therapy have a 13% risk of recurrence 5-20 years after diagnosis. 15 Studies have offered conflicting results on the efficacy of continuing endocrine therapy beyond five years. A series of randomized trials that compared the benefit of extended endocrine therapy (EET; 10 years total) versus the 5-year standard of care demonstrated that EET led to a modest clinical benefit in disease free survival, although many were confounded by the inclusion of patients who received adjuvant chemotherapy or by unknown hormone receptor status. 17-23