HERmark™ Collaborative Biomarker Study

The HERmark Collaborative Biomarker Study (CBS) is a retrospective, multi-center, observational biomarker study comparing conventional methods of HER2 testing against a quantitative HER2 total expression and HER2 homodimer assay (HERmark™)

Collaborative Biomarker Study will also collect data on HER1 (EGFR) and HER3 expression profiles, as measured by VeraTag™ assays, in this unselected population of women with breast cancer.

Rationale

Breast cancer patients are currently selected for trastuzumab therapy based on their HER2 status as determined by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) tests. Recently, the American Society of Clinical Oncology (ASCO), in collaboration with the College of American Pathologists (CAP)1, produced guidelines to improve testing accuracy and reduce the risks associated with false-positive and false-negative results. However, the best method to assess HER2 status remains controversial.

Additional members of the HER family of proteins, including HER1 and HER3, have been implicated as resistance pathways to trastuzumab and other therapies. The goal of the study is to understand quantitative measures of HER1, HER2 and HER3 expression and co-expression and their distribution in this population of women with breast cancer, as well as their association with tumor and disease characteristics and certain clinical outcomes. Such quantitative data on these HER family members, in a large cross section of breast cancer cases, are currently not available to the research community.

HERmark Collaborative Biomarker Study Objectives

1.  To compare quantitative measures of HER2 total expression and HER2 homodimers, as measured by HERmark™ , with conventional methods of HER2 testing (HER2 expression by IHC and/or HER2 gene amplification by FISH) performed at a central or local laboratory during the routine course of clinical evaluation of breast cancer patients.
2.  To describe other HER family (HER1/EGFR and HER3) protein expression and co-expression profiles as measured by quantitative VeraTag™ Research Use Only assays in a large and unselected set of breast tumors.
3.  To correlate expression profiles of HER family proteins measured in this study with tumor and disease characteristics and clinical outcomes.

Quantitative Measurement of Total HER1 and HER3 Protein Expression

Built on the VeraTag platform, assays for the measurement of total HER1 and HER3 protein expression are now available from Monogram Biosciences for Research Use Only.
  • Measure HER1 and HER3 total protein levels over a wide dynamic range
  • Identify potential resistance pathways for current HER2-targeted therapies

HERmark Collaborative Biomarker Study Sites

Physicians who routinely order HER2 tests (by IHC or FISH) on their patients undergoing breast cancer evaluation and treatment are invited to participate in this study. This retrospective study does not alter the practice patterns of participating physicians. No patient identifiers will be required.

Patient Inclusion Criteria
  • A histopathologic diagnosis of adenocarcinoma of the breast and either IHC staining for HER2 protein expression and/or FISH confirmation of HER2 gene amplification
  • Samples from the same tissue block must be available for HERmark testing
Specimen Requirements
  • FFPE tissue specimens from retrospective patient cases (specimens collected between Jan 2000 and May 2008)
  • 5 slides with one 5-µm section per positively charged glass slide
  • Monogram Biosciences will perform H&E staining, and certain acceptance criteria will apply

Patient Information to Be Provided to Monogram Biosciences

Participating physicians will be asked to complete a case report form, with patient de-identified information that includes but is not limited to:
  • HER2 results (IHC and/or FISH) by local or central laboratories
  • Estrogen receptor/progesterone receptor (ER/PR) status

Information to Be Provided to Participating Sites

  • A HERmark report for each patient case collected
  • At the conclusion of the study, data analysis of the total population will be reviewed by Monogram and the protocol committee
    • Results will be reviewed by and presented to investigators in the study
    • It is anticipated that after data analyses are complete, the data will be published or presented at a scientific conference
Authorship of publications and acknowledgement of contributions will be in accordance with standard academic and scientific practices .

Site Enrollment Criteria

  • 5 to 10 FFPE patient samples per site, retrospectively defined
  • Clinical study experience preferred
  • Individual sites can use Monogram's central Western Institutional Review Board (WIRB®)

1. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Arch Pathol Lab Med. 2007;131(1):18-43.