SUPERSEDED Local Coverage Determination (LCD)

MolDX: Breast Cancer Assay: Prosigna®

L36425

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Proposed LCD
Proposed LCDs are works in progress that are available on the Medicare Coverage Database site for public review. Proposed LCDs are not necessarily a reflection of the current policies or practices of the contractor.
Superseded
To see the currently-in-effect version of this document, go to the section.

Document Note

Note History

Contractor Information

LCD Information

Document Information

Source LCD ID
N/A
LCD ID
L36425
Original ICD-9 LCD ID
Not Applicable
LCD Title
MolDX: Breast Cancer Assay: Prosigna®
Proposed LCD in Comment Period
N/A
Source Proposed LCD
DL36425
Original Effective Date
For services performed on or after 02/01/2016
Revision Effective Date
For services performed on or after 03/02/2023
Revision Ending Date
02/14/2024
Retirement Date
N/A
Notice Period Start Date
12/17/2015
Notice Period End Date
01/31/2016
AMA CPT / ADA CDT / AHA NUBC Copyright Statement

CPT codes, descriptions and other data only are copyright 2023 American Medical Association. All Rights Reserved. Applicable FARS/HHSARS apply.

Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein.

Current Dental Terminology © 2023 American Dental Association. All rights reserved.

Copyright © 2023, the American Hospital Association, Chicago, Illinois. Reproduced with permission. No portion of the American Hospital Association (AHA) copyrighted materials contained within this publication may be copied without the express written consent of the AHA. AHA copyrighted materials including the UB‐04 codes and descriptions may not be removed, copied, or utilized within any software, product, service, solution or derivative work without the written consent of the AHA. If an entity wishes to utilize any AHA materials, please contact the AHA at 312‐893‐6816.

Making copies or utilizing the content of the UB‐04 Manual, including the codes and/or descriptions, for internal purposes, resale and/or to be used in any product or publication; creating any modified or derivative work of the UB‐04 Manual and/or codes and descriptions; and/or making any commercial use of UB‐04 Manual or any portion thereof, including the codes and/or descriptions, is only authorized with an express license from the American Hospital Association. The American Hospital Association (the "AHA") has not reviewed, and is not responsible for, the completeness or accuracy of any information contained in this material, nor was the AHA or any of its affiliates, involved in the preparation of this material, or the analysis of information provided in the material. The views and/or positions presented in the material do not necessarily represent the views of the AHA. CMS and its products and services are not endorsed by the AHA or any of its affiliates.

Issue

Issue Description

Annul review for policy, no changes made.

Issue - Explanation of Change Between Proposed LCD and Final LCD

CMS National Coverage Policy

Title XVIII of the Social Security Act (SSA), §1862(a)(1)(A), states that no Medicare payment shall be made for items or services that “are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.”

42 Code of Federal Regulations (CFR) §410.32 Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests and §80.1.1 Certification Changes

Coverage Guidance

Coverage Indications, Limitations, and/or Medical Necessity

This policy provides limited coverage of the Prosigna® Breast Cancer Gene Signature Assay to patients that meet the following criteria consistent with the United States (U.S.) Food and Drug Administration (FDA) indications for use:

  • Post-menopausal female either
    • ER+, lymph node-negative, stage I or II breast cancer; or
    • ER+, lymph node-positive (1-3 positive nodes), stage II breast cancer.



Claims for Prosigna® testing will be denied when testing does not meet all of the above criteria.

Background

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). Accordingly, Medicare has covered breast cancer gene signature prognostic/predictive tests since 2006.

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 Prosign®a 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 (FDA, 2013; FDA, 2015).

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 change 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).

Summary of Evidence

N/A

Analysis of Evidence (Rationale for Determination)

N/A

Proposed Process Information

Synopsis of Changes
Changes Fields Changed
N/A
Associated Information
Sources of Information
Bibliography
Open Meetings
Meeting Date Meeting States Meeting Information
N/A
Contractor Advisory Committee (CAC) Meetings
Meeting Date Meeting States Meeting Information
N/A
MAC Meeting Information URLs
N/A
Proposed LCD Posting Date
Comment Period Start Date
Comment Period End Date
Reason for Proposed LCD
Requestor Information
This request was MAC initiated.
Requestor Name Requestor Letter
N/A
Contact for Comments on Proposed LCD

Coding Information

Bill Type Codes

Code Description
N/A

Revenue Codes

Code Description
N/A

CPT/HCPCS Codes

Group 1

Group 1 Paragraph

N/A

Group 1 Codes

N/A

N/A

ICD-10-CM Codes that Support Medical Necessity

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

N/A

N/A

ICD-10-CM Codes that DO NOT Support Medical Necessity

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

N/A

N/A

Additional ICD-10 Information

General Information

Associated Information

Documentation Requirements

The patient's medical record must contain documentation that fully supports the medical necessity for services included within this LCD. (see “Coverage Indications, Limitations, and/or Medical Necessity") This documentation includes, but is not limited to, relevant medical history, physical examination, and results of pertinent diagnostic tests or procedures.

Documentation supporting the medical necessity should be legible, maintained in the patient's medical record, and must be made available to the MAC upon request.

Sources of Information

N/A

Bibliography
  1. Carlson JJ, & Roth JA. The impact of Oncotype DX breast cancer assay in clinical practice: A systematic review and meta-analysis. Breast Cancer Res Treat 2013;141:13-22.

  2. Chang JC, Makris A, Gutierrez MC, et al. Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients. Breast Cancer Res Treat 208;108:233-240.

  3. Dowsett M, Sestak I, Lopez-Knowles E, et al. Comparison of PAM50 Risk of Recurrence score with Oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy. J Clin Oncol. 2013; 31(22):2783-2790.

  4. FDA (2013). 510(k) Summary: K130010. Prosigna Breast Cancer Prognostic Gene Signature Assay. Accessed 03/03/2021.

  5. FDA (2015) Package Insert: Prosigna Breast Cancer Prognostic Gene Signature Assay. Accessed 03/03/2021. 

  6. Gnant M, Filipits M. Greil R,  et al. Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: Using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Ann Oncol 2013;25:339–345.

  7. Hernandez-Aya LF, Gonzalez-Angulo AM. Adjuvant systemic therapies in breast cancer. Surg Clin North Am . 2013  93(2):473–491.

  8. Martin M, Gonzalez-Rivera M, Morales S, et al.  Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer. Curr Med Res Opin 2015; 31 (6):1129-1137.

  9. Paoletti C, Hayes DF. Molecular testing in breast cancer. Ann Rev Med 2014; 65:95-110.

  10. Parker JS, Mullins M, Cheang MCU, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27(8):1160-1167.

  11. Rampurwala M, Rocque GB, Burkard ME. Update on adjuvant chemotherapy for early breast cancer. Breast Cancer: Basic and Clinical Research. 2014;8:125-134.

  12. Sestak I, Cuzick J, Dowsett M, et al. Prediction of late distant recurrence after 5 years of endocrine treatment: A combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and Arimidex, Tamozigen alone or in combination randomized trials using the PAM50 risk of recurrence score. J Clin Oncol. 2014;33:916-922.
  13.  

Revision History Information

Revision History Date Revision History Number Revision History Explanation Reasons for Change
03/02/2023 R14

R14

Revision Effective: 02/02/2023

Revision Explanation: Annual review, no changes made.

  • Other (Annual Review)
03/10/2022 R13

R13

Revision Effective: 03/10/2022

Revision Explanation: Annual review, no changes made.

  • Other (Annual Review)
04/22/2021 R12

R12

Revision Effective: 04/22/2021

Revision Explanation: LCD Title added a registered mark to Prosigna®. Under CMS National Coverage Policy added regulation CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests and §80.1.1 Certification Changes. Under Bibliography changes were made to citations to reflect AMA citation guidelines. Prosigna® was inserted throughout the LCD where applicable. Formatting, punctuation and typographical errors were corrected throughout the LCD. Acronyms were defined and inserted where appropriate throughout the LCD.

At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Provider Education/Guidance
09/23/2019 R11

R11

Revision Effective: n/a

Revision Explanation: Annual review, no changes made.

08/25/2020:At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Other (Annual Review)
09/23/2019 R10

R10

Revision Effective: 11/21/2019

Revision Explanation: Moved sources of information to the bibliography section. Removed the following regulations from the CMS National Policy section and placed into billing and coding article:

Title XVIII of the Social Security Act, §1833(e), prohibits Medicare payment for any claim lacking the necessary documentation to process the claim;

CMS Internet Online Manual Pub. 100-02 (Medicare Benefit Policy Manual), Chapter 15, Section 80, “Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests”;

CMS Internet-Only Manuals, Publication 100-04, Medicare Claims Processing Manual, Chapter 16, §50.5 Jurisdiction of Laboratory Claims, 60.12 Independent Laboratory Specimen Drawing, 60.2. Travel Allowance; and

CMS Internet Online Manual Pub. 100-04 (Medicare Claims Processing Manual), Chapter 23 (Section 10) “Reporting ICD Diagnosis and Procedure Codes”.

11/21/2019:At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Provider Education/Guidance
09/23/2019 R9

R9

Revision Effective: 09/23/2019 Revision Explanation: Annual review, no changes made.

09/23/2019:At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Other (Annual Review, no changes made)
09/19/2019 R8

R8

Revision Effective: 09/19/2019 Revision Explanation: Converted policy into new policy template that no longer includes coding section based on CR 10901. For Approval, no changes.

09/13/2019:At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Revisions Due To Code Removal
09/19/2019 R7

R7

Revision Effective: 09/19/2019 Revision Explanation: Converted policy into new policy template that no longer includes coding section based on CR 10901.

09/12/2019:At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Revisions Due To Code Removal
09/05/2019 R6

R6

Revision Effective: 09/05/2019

Revision Explanation: All coding located in the Coding Information section has been moved into the related Billing and Coding: MolDX: Breast Cancer Assay: Prosigna A56989 article and removed from the LCD.

  • Provider Education/Guidance
01/01/2018 R5

R5

Revision Effective: N/A

Revision Explanation: Annual review no changes made.

DATE (08/27/2019): At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Other (Annual Review)
01/01/2018 R4

R4

Revision Effective: N/A

Revision Explanation: Annual review no changes made.

DATE (08/13/2018): At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Other (Annual Review)
01/01/2018 R3

R3

Revision Effective: 01/01/2018

Revision Explanation: Remove 0008M and replaced with new code 81520 due to annual HCPCS update. Corrected some formatting in text.

DATE (12/13/2017): At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Revisions Due To CPT/HCPCS Code Changes
02/01/2016 R2

R2

Revision Effective: N/A

Revision Explanation: Annual review no changes made.

DATE (08/28/2017): At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.


  • Other (Annual review)
02/01/2016 R1 R1
Revision Effective: N/A
Revision Explanation: Annual review no changes made.
  • Other (Annual Review)
N/A

Associated Documents

Attachments
N/A
Related National Coverage Documents
N/A
Public Versions
Updated On Effective Dates Status
02/06/2024 02/15/2024 - N/A Currently in Effect View
02/20/2023 03/02/2023 - 02/14/2024 Superseded You are here
Some older versions have been archived. Please visit the MCD Archive Site to retrieve them.

Keywords

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