ASCO BREAST CANCER BIOMARKERS GUIDELINES

The American Society of Clinical Oncology (ASCO) has published new clinical practice guidelines on the use of biomarkers to guide decisions about systemic adjuvant therapy for women with early-stage invasive breast cancer and known estrogen-receptor (ER), progesterone-receptor (PR), and HER2status.

The updated guidelines, published online on February 8 in the Journal of Clinical Oncology, use more rigorous criteria to evaluate the evidence base than the 2007 biomarker guidelines, according to Lyndsay N. Harris, MD, director of the breast cancer program at Case Western University in Cleveland, and members of a biomarker expert panel.

The guidelines address two main issues: Which biomarkers have clinical utility in guiding decisions about adjuvant systemic therapy?; and which biomarkers guide the choice of specific drugs or regimens?

To update the guidelines, Dr Harris and the panel conducted a systematic literature review of studies published from 2006 to 2014. The search identified one randomized clinical trial and 18 prospective-retrospective studies that evaluated the clinical utility of specific biomarkers to guide decisions about adjuvant systemic therapy.

Clinical utility was defined as "a favorable balance of benefits to harms compared with treatment of the patient in the absence of the biomarker test result." Analytic and clinical validity were also evaluated.

The panel found "sufficient evidence" of clinical utility to recommend assays that identify ER, PR, and HER2 receptor status, and six biomarker assays in specific subgroups of patients with breast cancer: Oncotype DX (Genomic Health), EndoPredict (Sividon Diagnostics), PAM50 (Prosigna Breast Cancer Prognostic Gene Signature Assay), Breast Cancer Index, urokinase plasminogen activator, and plasminogen activator inhibitor type 1.

According to the panel, only ER, PR, and HER2 status can guide decisions about specific treatments.

There are differences in insurance coverage and issues of racial and ethnic disparities in cancer care, the panel notes, and ER/PR and HER2 expression and biomarker testing can vary across ethnic and racial backgrounds. Treatment plans should include chronic conditions, and decision-making should be shared.

"Clinicians should educate patients, family members, and/or caregivers about the results of pathology tests and how they use them to develop a treatment plan tailored to the biology of the cancer," the panel concludes. "Because many patients who receive a new diagnosis are under emotional stress and/or may be unaccustomed to complex medical terminology, the use of easily understood language, at an educational level that the patient can understand, is key to clear communication."

Table. Recommendations on the Use of Biomarkers to Guide Decisions About Adjuvant Systemic Therapy

The Oncotype DX 21-gene recurrence score may be used in patients with ER/PR-positive, HER2-negative (node-negative) breast cancer (strength of recommendation: strong). However, it should not be used in patients with HER2-positive or triple-negative breast cancer.

The EndoPredict 12-gene risk score may be used in patients with ER/PR-positive, HER2-negative (node-negative) breast cancer (strength of recommendation: moderate). However, it should not be used in patients with ER/PR-positive, HER2-negative (node-positive) breast cancer, nor in patients with HER2-positive or triple-negative breast cancer.

The MammaPrint (Agendia) 70-gene assay should not be used in patients with triple-negative breast cancer; in patients with ER/PR-positive, HER2-negative (node-positive or node-negative) breast cancer; nor in patients with HER2-positive breast cancer.

PAM50 risk of recurrence score may be used, in combination with other clinicopathologic variables, in patients with ER/PR-positive, HER2-negative (node-negative) breast cancer (strength of recommendation: strong). However, it should not be used in patients with ER/PR-positive, HER2-negative (node-positive) breast cancer, nor in patients with HER2-positive or triple-negative breast cancer.

The Breast Cancer Index may be used in patients with ER/PR-positive, HER2-negative (node-negative) breast cancer (strength of recommendation: moderate). However, it should not be used in patients with ER/PR-positive, HER2-negative (node-positive) breast cancer, nor in patients with HER2-positive or triple-negative breast cancer.

The Mammostrat (Clarient) five-protein assay should not be used in patients with ER/PR-positive, HER2-negative (node-positive or node-negative) breast cancer, nor in patients with HER2-positive or triple-negative breast cancer.

Immunohistochemistry 4 may be used in patients with ER/PR-positive, HER2-negative (node-negative) breast cancer (strength of recommendation: moderate). However, it should not be used in patients with HER2-positive or triple-negative breast cancer.

Urokinase plasminogen activator and plasminogen activator inhibitor type 1 may be used in patients with ER/PR-positive, HER2-negative (node-negative) breast cancer (strength of recommendation: weak). However, they should not be used in patients with HER2-positive breast cancer or triple-negative breast cancer.

Circulating tumor cells should not be used to guide decisions on adjuvant systemic therapy.

Tumor infiltrating lymphocytes should not be used in patients with ER/PR-positive, HER2-negative (node-positive or node-negative) breast cancer, nor in patients with HER2-positive or triple-negative breast cancer.

Protein encoded by the MKI67 gene should not be used to guide the selection of adjuvant chemotherapy.

CYP2D6 polymorphisms or p27 expression determined by immunohistochemistry should not be used to guide the selection of adjuvant tamoxifen.

Protein encoded by the immunohistochemistry MKI67 gene labeling index should not be used to guide the selection of adjuvant aromatase inhibitors.

For patients with ER/PR-positive, HER2-negative (node-negative) breast cancer who have had 5 years of endocrine therapy without evidence of recurrence, clinicians should not use multiparameter gene expression or protein assays (Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, or immunohistochemistry 4) to guide decisions on extended endocrine therapy.

Clinicians should not use microtubule-associated protein Tau messenger (m)RNA expression or mRNA expression determined by immunohistochemistry, nor HER1/epidermal growth-factor receptor expression by immunohistochemistry, to guide the selection of adjuvant taxanes.

Clinicians should not use TOP2A gene amplification or TOP2A protein expression determined by immunohistochemistry, and should not use HER2 and TOP2A gene coamplification, CEP17 duplication, TIMP-1, FOXP3, nor p53 to guide the selection of adjuvant anthracyclines.

Guidelines on the use of biomarkers to guide decisions about systemic therapy in metastatic breast cancer were released by ASCO last year (J Clin Oncol. 2015;33:2695-2704).

One or more of the authors report financial relationships with Philips Research, GlaxoSmithKline, AstraZeneca, Novartis, Pfizer, Eisai, Eli Lilly, Servier, Merck, Roche, Daiichi Sankyo, Janssen Pharmaceuticals, Hospira, Amgen, Seattle Genetics, Celgene, Veridex, Clearbridge Biomedics, Genetech, Bayer AG, UpToDate, Arrien Pharmaceuticals, Fujirebio Diagnostics, Oncimmune, Inbiomotion, and/or Puma Biotechnology. Coauthor Nofisat Ismaila, MD, is an employee of GlaxoSmithKline. Coauthor Robert Mennel, MD, from the Baylor University Medical Center in Dallas, is an employee of Texas Oncology. Coauthor Daniel Hayes, MD, from the University of Michigan Comprehensive Cancer Center in Ann Arbor, holds three patents for technologies related to the diagnosis and treatment of breast cancer.

J Clin Oncol. Published online February 8, 2016. Abstract