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The rules say that plans must pay for a medical service or item if regular Medicare would pay for it in this case. 
You can find this rule at 42 Code of Federal Regulations (CFR) Section 422.101. 
 
The rules say covered clinical types of application(s) are identified below as diagnostic (DX), prognostic 
(PROG) or predictive (PRED). 
 
Women with early breast cancer and up to 3 locally positive lymph nodes whose tumor is estrogen-receptor 
positive will usually receive anti-hormonal therapy such as tamoxifen or aromatase inhibitors. U.S. (NCCN) 
and international (St. Gallen) guidelines predicate the decision for adjuvant chemotherapy on the size and grade 
of the breast cancer and other factors including genomic assays that provide additional information on risk of 
recurrence (Hernandez-Ava et al., 2013). According to a 2014 review, Prognostic factors provide an 
indication of whether a patient needs subsequent therapy. (Paoletti & Hayes, 2014). Similarly, another 2014 
review article states, Efforts should be focused on reducing chemotherapy in patients unlikely to benefit. 
(Rampurwala et al., 2014). 
 
The PAM50 breast cancer gene signature test was developed in the late 1990s and initial studies showed a 
strong correlation with breast cancer recurrence and with complete pathologic response to neoadjuvant 
chemotherapy (Parker et al., 2009). While test results are reported on a scale of 1-100 as a Risk of Recurrence 
(ROR) score, the underlying algorithm is also able to classify cases into the luminal A and B, Her2neu, and 
triple-negative subtype classifications. 
 
The Nanostring nCounter nucleic acid analysis system replicates the PAM50 algorithm, as an FDA cleared 
kit, the Prosigna Breast Cancer Gene Signature Assay (FDA, 2013). The Prosigna package insert was most 
recently updated in January, 2015 (FDA, 2015) reflecting additional studies (Sestak et al., 2014). Notably, the 
Prosigna platform and the original PAM50 platform have a 0.997 correlation (Dowsett et al., 2013). 
 
For the FDA, the Prosigna test was validated in a large population of post-menopausal, estrogen-receptor 
positive women based on 1,017 cases of the TransATAC study (Dowsett et al., 2013). The study showed a 
strong correlation with long-term breast cancer recurrence and added substantial additional prognostic 
information over a clinical treatment score based on standard clinical variables. This study was replicated in an independent population, also on the Prosigna test, using 1,620 samples from the ABCSG8 trial (Gnant, 2014). 
A separate analysis of these trials validated prediction of distant recurrence in years 5-10 after initial diagnosis 
(Sestak et al., 2014) and has been incorporated in the FDA labeling (FDA, 2015). The Prosigna test is issued as 
separate reports, consistent with FDA review and labeling, for node-negative and node-positive (1-3 node) 
populations. Analytic performance, precision, reproducibility, and analysis of the clinical validations are 
provided in the FDA labeling (https://www.accessdata.fda.gov/cdrh_docs/reviews/K130010.pdf). 
 
Clinical utility of this breast cancer gene signature has also been assessed. The study of Martin et al. (2015) 
showed a 20% decision impact on decisions for or against adjuvant chemotherapy in an all-comers population 
of 200 new cases of incident breast cancer, when Prosigna test information became available after all other 
clinical information had been considered. The net rates of selecting adjuvant chemotherapy for low, 
intermediate, and high risk cases was similar to that observed in a meta-analysis of Oncotype DX decision data 
(Carlson & Roth, 2013). Additional support for the use of these test results in treatment decisions comes from 
Parker et al. (2009), in which there was a strong association with neoadjuvant chemotherapy response. Low-
scoring cases have a very low chance of complete pathological response to neoadjuvant chemotherapy, while 
high-scoring cases approach a 50% chance of complete pathological response. The same findings have been 
observed for other breast cancer gene signatures based on prognostic algorithms (Chang et al., 2008).  
 
The Prosigna test is reasonable and necessary when performed according to the FDA label 
(https://www.accessdata.fda.gov/cdrh_docs/reviews/K130010.pdf). 
 
21.  Bladder 
 
CDKN2A  PROG 
FGFR1  PROG 
FGFR3  PROG 
MTOR  PROG 
PIK3CA  DX and PROG 
PTEN  PROG 
RB1  PROG 
TP53 - PROG 
 
You can find this information in Medicare's Local Coverage Determination (LCD): Biomarkers for Oncology 
(L35396). 
 
If you want to read these Medicare rules, you can go to this website www.medicareappeal.com.