Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer

Effective 1-15-2021

• Updated Description Section
• Updated Medical Policy Section

Removed Item A: The use of Oncotype DX, EndoPredict, the Breast Cancer Index, MammaPrint, and Prosigna to determine recurrence risk for deciding whether to undergo adjuvant chemotherapy may be considered medically necessary in individuals with primary, invasive breast cancer meeting ALL of the following characteristics:

Added Item A The use of the 21-gene reverse transcriptase-polymerase chain reaction (RT-PCR) assay (ie, Oncotype DX) to determine recurrence risk for deciding whether to undergo adjuvant chemotherapy may be considered medically necessary in women with primary, invasive breast cancer meeting all of the following characteristics:

Added Item B The use of the MammaPrint assay to determine recurrence risk for deciding whether to undergo adjuvant chemotherapy may be considered medically necessary in women with primary, invasive breast cancer meeting all of the following characteristics:

1. Unilateral tumor;
2. Hormone receptor-positive (ie, estrogen receptor-positive or progesterone receptorpositive);
3. Human epidermal growth factor receptor 2-negative;
4. Stage T1 or T2 or operable T3 at high clinical risk (see Policy Guidelines);
5. One to three positive nodes;
6. Who will be treated with adjuvant endocrine therapy (eg, tamoxifen, aromatase inhibitors);
7. When the test result aids the patient in deciding on chemotherapy (ie, when chemotherapy is a therapeutic option); AND
8. When ordered within 6 months after diagnosis, because the value of the test for making decisions regarding delayed chemotherapy is unknown.

Removed Item B The 21-gene RT-PCR assay Oncotype DX should only be ordered on a tissue specimen obtained during surgical removal of the tumor and after subsequent pathology examination of the tumor has been completed and determined to meet the above criteria (ie, the test should not be ordered on a preliminary core biopsy). The test should be ordered in the context of a physician-patient discussion regarding risk preferences when the test result will aid in making decisions regarding chemotherapy.

Added Item E All other indications “for the 21-gene RT-PCR assay” (ie,for Oncotype DX, EndoPredict, the Breast Cancer Index, MammaPrint, and Prosigna, including determination of recurrence

risk in invasive breast cancer patients with positive lymph nodes, patients with bilateral disease, or to consider length of treatment with tamoxifen, are considered experimental / investigational. Added Item F Use of gene expression assays in men with breast cancer is considered experimental/investigational.

Added Policy Guidelines

In the MINDACT trial (Cardoso 2016), low versus high clinical risk was determined using the Adjuvant! Online tool (version 8.0 with HER2 status, www.adjuvantonline.com). The Adjuvant tool includes factors for age, comorbidities, ER status, tumor grade and size and number of positive nodes.

In MINDACT, ER-positive, HER2-negative, node-positive patients were classified as high clinical risk if they met any of the following additional criteria:

• Grade: well differentiated; tumor size, <= 2 cm or 2.1 to 5 cm • Grade: moderately differentiated; tumor size, any size
• Grade: poorly differentiated or undifferentiated; tumor size, any size See the Codes table for details.
• Updated Code Section Added CPT 81522, 81599

Source: https://www.bcbsks.com/CustomerService/Providers/MedicalPolicies/policies/policies/Assays_GeneticExpression_TumorTissue_Technique_DeterminePrognosis_Patients_BreastCancer_2021-01-15.pdf