This document addresses the use of genetic profiling of breast tumors to predict breast cancer recurrence and response to therapy.

Clinical Indications

Medically Necessary:

Gene expression profiling for breast cancer is considered medically necessary in the following situations:

1. Gene expression profiling with the Oncotype DX^® Breast Recurrence Score, EndoPredict^®, Prosigna^® Breast Cancer Prognostic Gene Signature Assay, the Breast Cancer Index^℠ or MammaPrint^® as a technique for managing the treatment of breast cancer when all of the following criteria are met:
   1. Individual has had surgery and full pathological evaluation of the specimen has been completed; and
   2. Histology is ductal, lobular, mixed, or metaplastic; and
   3. Estrogen receptor positive (ER+), or progesterone receptor positive (PR+), or both; and
   4. HER2 (human epidermal growth factor receptor-2) receptor negative; and
   5. pN0 (node negative) or pN1mi with axillary lymph node micrometastasis less than or equal to 2 mm; and
   6. T1b to T3 (tumor size greater than 0.5 cm and less than or equal to 5.0 cm); and
   7. Chemotherapy is a therapeutic option being considered by the individual and their provider; and
   8. No other breast cancer gene expression profiling assay has been conducted for the same tumor (for example a metastatic focus) or from more than one site when the primary tumor is multifocal.
      OR
2. Use of gene expression profiling with the Oncotype DX Breast Recurrence Score for postmenopausal individuals with 1-3 positive lymph nodes (pN1a, pN1b or pN1c) when criteria A, B, C, D, F, G and H above have been met.
   OR
3. Use of gene expression profiling with EndoPredict, Prosigna Breast Cancer Prognostic Gene Signature Assay, or the Breast Cancer Index as a genetic index used to assist in decisions of extending adjuvant hormonal therapy beyond 5 years of treatment when all of the following criteria are met:
   1. When criteria A through F above have been met; and
   2. When the Oncotype DX Breast Recurrence Score was the initial gene expression profiling test used, and
   3. The individual is a candidate for additional cancer therapy.
      OR
4. Use of gene expression profiling with the Breast Cancer Index as a genetic index used to assist in decisions of extending adjuvant hormonal therapy beyond 5 years of treatment for individuals with 1-3 positive lymph nodes (pN1a, pN1b or pN1c) is considered medically necessary when all of the following criteria are met:
   1. When criteria A through D above have been met; and
   2. When the Oncotype DX Breast Recurrence Score was the initial gene expression profiling test used, and
   3. The individual is a candidate for additional hormonal or chemotherapy.

Not Medically Necessary:

Gene expression profiling with the Oncotype DX Breast Recurrence Score, EndoPredict, Prosigna Breast Cancer Prognostic Gene Signature Assay, the Breast Cancer Index or MammaPrint as a technique of managing the treatment of breast cancer is considered not medically necessary when the criteria above have not been met, including but not limited to in individuals with known metastatic cancer.

Gene expression profiling as a technique of managing the treatment of ductal carcinoma in situ (DCIS) (when DCIS is the sole breast cancer histology) is considered not medically necessary under all circumstances.

Repeat gene expression profiling with the Oncotype DX Breast Recurrence Score, EndoPredict, Prosigna Breast Cancer Prognostic Gene Signature Assay, the Breast Cancer Index, or MammaPrint for the same tumor (for example a metastatic focus) or from more than one site when the primary tumor is multifocal is considered not medically necessary.

Gene expression profiling as a technique of managing the treatment of breast cancer is considered not medically necessary when a gene profiling test other than the Oncotype DX Breast Recurrence Score, EndoPredict, Prosigna Breast Cancer Prognostic Gene Signature Assay, the Breast Cancer Index or MammaPrint is being used, including but not limited to:

1. BluePrint^™ (also referred to as “80-gene profile”)
2. BreastOncPX^™
3. BreastPRS
4. Insight TNBCtype^™
5. Mammostrat
6. MammaTyper^®
7. NexCourse^® Breast IHC4
8. NuvoSelect^™ eRx 200-Gene Assay
9. Oncotype DX^® Breast DCIS Score
10. PAM50 Breast Cancer Intrinsic Classifier^™
11. SYMPHONY^™ Genomic Breast Cancer Profile
12. TargetPrint^®
13. TheraPrint ^™
14. The 41-gene signature assay
15. The 76-gene “Rotterdam signature” assay