Welcome to NGC. Skip directly to: Search Box, Navigation, Content.

Brief Summary

GUIDELINE TITLE

American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.

BIBLIOGRAPHIC SOURCE(S)

GUIDELINE STATUS

This is the current release of the guideline.

BRIEF SUMMARY CONTENT

 RECOMMENDATIONS
 EVIDENCE SUPPORTING THE RECOMMENDATIONS
 IDENTIFYING INFORMATION AND AVAILABILITY
 DISCLAIMER

 Go to the Complete Summary

RECOMMENDATIONS

MAJOR RECOMMENDATIONS

Optimal algorithm for human HER2 testing Positive for HER2 is either IHC HER2 3+ (defined as uniform intense membrane staining of > 30% of invasive tumor cells) or FISH amplified (ratio of HER2 to CEP17 of > 2.2 or average HER2 gene copy number > six signals/nucleus for those test systems without an internal control probe)

Equivocal for HER2 is defined as either IHC 2+ or FISH ratio of 1.8-2.2 or average HER2 gene copy number four to six signals/nucleus for test systems without an internal control probe

Negative for HER2 is defined as either IHC 0-1+ or FISH ratio of <1.8 or average HER2 gene copy number of < four signals/nucleus for test systems without an internal control probe

These definitions depend on laboratory documentation of the following:
  1. Proof of initial testing validation in which positive and negative HER2 categories are 95% concordant with alternative validated method or same validated method for HER2
  2. Ongoing internal QA procedures
  3. Participation in external proficiency testing
  4. Current accreditation by valid accrediting agency
Optimal FISH testing requirements Fixation for fewer than 6 hours or longer than 48 hours is not recommended

Test is rejected and repeated if:
  • Controls are not as expected
  • Observer cannot find and count at least two areas of invasive tumor
  • > 25% of signals are unscorable due to weak signals
  • > 10% of signals occur over cytoplasm
  • Nuclear resolution is poor
  • Autofluorescence is strong
Interpretation done by counting at least 20 cells; a pathologist must confirm that counting involved invasive tumor

Sample is subjected to increased counting and/or repeated if equivocal; report must include guideline-detailed elements (see Table 10 in the original guideline document)
Optimal IHC testing requirements Fixation for fewer than 6 hours or longer than 48 hours is not recommended

Test is rejected and repeated or tested by FISH if:
  • Controls are not as expected
  • Artifacts involve most of sample
  • Sample has strong membrane staining of normal breast ducts (internal controls)
Interpretation follows guideline recommendation:
  • Positive HER2 result requires homogeneous, dark circumferential (chicken wire) pattern in > 30% of invasive tumor
  • Interpreters have method to maintain consistency and competency
Sample is subjected to confirmatory FISH testing if equivocal based on initial results

Report must include guideline-detailed elements (see Table 9 in the original guideline document)
Optimal tissue handling requirements Time from tissue acquisition to fixation should be as short as possible; samples for HER2 testing are fixed in neutral buffered formalin for 6 to 48 hours; samples should be sliced at 5 to 10 mm intervals after appropriate gross inspection and margins designation and placed in sufficient volume of neutral buffered formalin

Sections should ideally not be used for HER2 testing if cut > 6 weeks earlier; this may vary with primary fixation or storage conditions

Time to fixation and duration of fixation if available should be recorded for each sample
Optimal internal validation procedure Validation of test must be done before test is offered

Initial test validation requires 25 to 100 samples tested by alternative validated method in the same laboratory or by validated method in another laboratory

Proof of initial testing validation in which positive and negative HER2 categories are 95% concordant with alternative validated method or same validated method for HER2

Ongoing validation should be done biannually
Optimal internal QA procedures Initial test validation

Ongoing quality control and equipment maintenance

Initial and ongoing laboratory personnel training and competency assessment

Use of standardized operating procedures including routine use of control materials

Revalidation of procedure if changed

Ongoing competency assessment and education of pathologists
Optimal external proficiency assessment Participation in external proficiency testing program with at least two testing events (mailings)/year

Satisfactory performance requires at least 90% correct responses on graded challenges for either test
  • Unsatisfactory performance will require laboratory to respond according to accreditation agency program requirements
Optimal laboratory accreditation Onsite inspection every other year with annual requirement for self-inspection
  • Reviews laboratory validation, procedures, QA results and processes, results and reports
  • Unsatisfactory performance results in suspension of laboratory testing for HER2 for that method

Abbreviations: HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; FISH, fluorescent in situ hybridization; QA, quality assurance

CLINICAL ALGORITHM(S)

Algorithms are provided in the original guideline document for:

  • Immunohistochemistry (IHC)
  • Fluorescent in situ hybridization (FISH)
Top^

EVIDENCE SUPPORTING THE RECOMMENDATIONS

TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The evidence supporting each recommendation is presented in the original guideline document under "Review of Relevant Literature." In general, the literature review supporting these recommendations centered on consensus conferences held in the United States, single institution studies, experience from reference laboratories, international reports, regulations currently in force in the United States (Clinical Laboratory Improvement Amendment [CLIA] 88 and US Food and Drug Administration regulations), and expert consensus at the panel meeting.

Top^

IDENTIFYING INFORMATION AND AVAILABILITY

BIBLIOGRAPHIC SOURCE(S)

ADAPTATION

Not applicable: The guideline was not adapted from another source.

DATE RELEASED

2007 Jan 1

GUIDELINE DEVELOPER(S)

American Society of Clinical Oncology - Medical Specialty Society
College of American Pathologists - Medical Specialty Society

SOURCE(S) OF FUNDING

American Society of Clinical Oncology

College of American Pathologists

GUIDELINE COMMITTEE

ASCO/CAP Expert Panel on Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer

COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

Panel Members: Antonio C. Wolff; M. Elizabeth H. Hammond; Jared N. Schwartz; Karen L. Hagerty; D. Craig Allred; Richard J. Cote; Mitchell Dowsett; Patrick L. Fitzgibbons; Wedad M. Hanna; Amy Langer; Lisa M. McShane; Soonmyung Paik; Mark D. Pegram; Edith A. Perez; Michael F. Press; Anthony Rhodes; Catharine Sturgeon; Sheila E. Taube; Raymond Tubbs; Gail H. Vance; Marc van de Vijver; Thomas M. Wheeler; Daniel F. Hayes

FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment: N/A

Leadership: N/A

Consultant: Richard J. Cote, Clarient, Roche, Abbott; Mitchell Dowsett, Roche, Abbott Diagnostics; Soonmyung Paik, Genentech, GlaxoSmithKline; Mark D. Pegram, Genetech; Michael F. Press, Genentech; Anthony Rhodes, European Collection of Cell Cultures; Marc van de Vijver, Roche; Daniel F. Hayes, Immunicon, Pfizer, Novartis

Stock: Richard J. Cote, Clarient

Honoraria: M. Elizabeth H. Hammond, M2 Communications, Serinomics; Mitch Dowsett, Roche; Soonmyung Paik, Genentech, GlaxoSmithKline; Mark D. Pegram, Genentech; Michael F. Press, Genentech; Raymond Tubbs, Ventana, Abbott/Vysis; Marc van de Vijver, Roche

Research Funds: Antonio C. Wolff, Roche; Richard J. Cote, Roche, Abbott; Raymond Tubbs, Ventana, Abbott/Vysis; Daniel F. Hayes, Pfizer, Novartis

Testimony: Michael F. Press, Genentech

Other: Raymond Tubbs, Nanoprobes

GUIDELINE STATUS

This is the current release of the guideline.

GUIDELINE AVAILABILITY

Electronic copies: Available in from the American Society of Clinical Oncology (ASCO) Web site. Also available from the College of American Pathologists (CAP) Web site.

Print copies: Available from American Society of Clinical Oncology, Cancer Policy and Clinical Affairs, 1900 Duke Street, Suite 200, Alexandria, VA 22314; E-mail: guidelines@asco.org.

AVAILABILITY OF COMPANION DOCUMENTS

The following is available:

Electronic copies: Available in Portable Document Format (PDF) from the American Society of Clinical Oncology (ASCO) Web site. Also available from the College of American Pathologists (CAP) Web site.

Guidelines are available for Personal Digital Assistant (PDA) download from the ASCO Web site.

PATIENT RESOURCES

The following is available:

Please note: This patient information is intended to provide health professionals with information to share with their patients to help them better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether or not it accurately reflects the original guideline's content.

NGC STATUS

This NGC summary was completed by ECRI on February 21, 2007. The information was verified by the guideline developer on February 22, 2007.

COPYRIGHT STATEMENT

This summary is based on the original guideline, which is subject to the American Society of Clinical Oncology's copyright restrictions.

Top^

DISCLAIMER

NGC DISCLAIMER

The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

All guidelines summarized by NGC and hosted on our site are produced under the auspices of medical specialty societies, relevant professional associations, public or private organizations, other government agencies, health care organizations or plans, and similar entities.

Guidelines represented on the NGC Web site are submitted by guideline developers, and are screened solely to determine that they meet the NGC Inclusion Criteria which may be found at http://www.guideline.gov/about/inclusion.aspx .

NGC, AHRQ, and its contractor ECRI Institute make no warranties concerning the content or clinical efficacy or effectiveness of the clinical practice guidelines and related materials represented on this site. Moreover, the views and opinions of developers or authors of guidelines represented on this site do not necessarily state or reflect those of NGC, AHRQ, or its contractor ECRI Institute, and inclusion or hosting of guidelines in NGC may not be used for advertising or commercial endorsement purposes.

Readers with questions regarding guideline content are directed to contact the guideline developer.
Top^

 


Search Help
Detailed Search
Frequent Searches

Summary

Brief Summary
Complete Summary
XML View
Full Text
Palm Download
MS Word
Adobe PDF

Browse

» Disease / Condition
» Treatment / Intervention
» Measures
» Organization
» Guideline Index
» Guidelines In Progress
» Guideline Archive

Compare

» View My Collection
» Add to My Collection
» Guideline Syntheses

 

   
DHHS Logo