Highmark Commercial Medical Policy - Pennsylvania

Medical Policy: L-215-002
Topic: PALB2 Genetic Testing for Breast Cancer Risk
Section: Laboratory
Effective Date: July 1, 2018
Issue Date: July 2, 2018
Last Reviewed: March 2018

Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancer mortality in women around the world. Hereditary breast cancer accounts for 5% to 10% of all breast cancer cases.In particular, two cancer susceptibility genes, BRCA1 and BRCA2, are implicated in about 20% of all hereditary breast cancer cases. Other genes have also been identified in the literature; in particular, PALB2 is a gene that encodes a protein that may be involved in tumor suppression, and is considered a partner and localizer of BRCA2. Specifically, ~50 truncating mutations in PALB2 have been detected among breast cancer families worldwide.

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member’s benefit plan.

Known Familial Mutation Analysis

PALB2 genetic testing for a known familial mutation analysis may be considered medically necessary when ALL of the following are met:

·         Genetic Counseling:

o    Pre- and post-test genetic counseling by an appropriate provider (as deemed by the Health Plan policy); and

·         Previous Genetic Testing:

o    No previous full sequence testing or deletion/duplication analysis; and

o    Known family mutation in PALB2 identified in 1st, 2nd, or 3rd degree relative(s); and

·         Age 18 years or older.

Procedure Codes

Full Sequence Analysis

Full sequence analysis of the PALB2 gene may be considered medically necessary when ALL of the following are met:

 **Please see the guideline BRCA Analysis for criteria

Procedure Codes

Professional Statements and Societal Positions

The National Comprehensive Cancer Network (NCCN, 2017) includes breast cancer risk and management recommendations for individuals with PALB2 in a table located in their Genetic/Familial High-Risk Assessment: Breast and Ovarian guideline. However, it is noted that, “The inclusion of a gene on this table below does not imply endorsement either for or against multi-gene testing for moderate penetrance genes.” Recommendations are as follows:

  • “Screening: Annual mammogram and consider breast MRI with contrast at 30y.
  • RRM: Consider based on family history.”

The European Society for Medical Oncology (ESMO, 2016) states the following prevention and screening strategies for individuals with a PALB2 mutation:

  • “Clinical breast examination every 6-12 months staring from age 20-25
  •  Annual breast MRI from age 20-29
  •  Annual breast MRI and/or mammogram at age 30-87.”

ESMO (2016) also states the following regarding PALB2 testing, “The following genes might have moderate- to high-penetrance germline mutations for breast or ovarian cancer: p53, PTEN, CDH1, PALB2, CHEK2, ATM, RAD51C, STK11, RAD51D, BRIP1, MLH1, MSH, MSH6, and PMS2. Prevention and screening strategies for these mutations are summarized in Table 1 – due to limited research in individuals harboring these mutations, the level of evidence for these recommendations is mostly expert opinion, and a full discussion is beyond the scope of these guidelines.”

The Second International Consensus Conference for Breast Cancer in Young Women (BCY2, 2016) led to publication of consensus recommendations. The following is stated regarding PALB2 genetic testing:

  • “Other moderate-high-penetrance genes (e.g., CDH1, CHEK2, PALB2, RAD51C, BRIP1) should be tested for as deemed necessary by the geneticist.”

A review of the available PALB2 literature revealed the following:

  • Direct evidence from a number of case control studies reporting relative risk and odds ratio values suggest that PALB2 testing accurately identifies PALB2 mutations, which are associated with an increased risk of developing breast cancer. Indirect evidence suggests that the clinical utility of PALB2 testing may alter clinical decision making enough to lead to improved patient health outcomes.
  • Direct and indirect evidence regarding clinical validity and clinical utility suggest that expanded panel testing may be used to identify more women who can benefit from appropriate breast cancer risk reduction strategies. However, gaps in knowledge persist regarding the precise cancer risk estimates for PALB2 (e.g., wide confidence intervals) and the predictive value in individuals and relatives who test negative for pathogenic variants yet have a strong family history of disease.
  • Before clinical utility of PALB2 testing can be adequately established, well designed studies are crucial to directly evaluate the clinical utility of PALB2 to alter treatment and overall disease management strategies and improve morbidity and mortality outcomes in women who develop hereditary breast cancer

Place of Service: Outpatient

PALB2 testing is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

The policy position applies to all commercial lines of business

Denial Statements

Services that do not meet the criteria of this policy will not be considered medically necessary. A network provider cannot bill the member for the denied service unless: (a) the provider has given advance written notice, informing the member that the service may be deemed not medically necessary; (b) the member is provided with an estimate of the cost; and (c) the member agrees in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.


Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer: If you need these services, contact the Civil Rights Coordinator.

If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

Insurance or benefit/claims administration may be provided by Highmark, Highmark Choice Company, Highmark Coverage Advantage, Highmark Health Insurance Company, First Priority Life Insurance Company, First Priority Health, Highmark Benefits Group, Highmark Select Resources, Highmark Senior Solutions Company or Highmark Senior Health Company, all of which are independent licensees of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield plans.

Highmark retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.