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ASCO Guideline Clarifies Biomarker Assay Use in Adjuvant Breast Cancer Care

Gina Columbus @ginacolumbusonc
Published: Monday, Feb 08, 2016

Lyndsay N. Harris, MD

Lyndsay N. Harris, MD

ASCO released new evidence-based recommendations to ensure appropriate use of biomarker assay results in guiding decisions on adjuvant therapy for women with early-stage invasive breast cancer and known estrogen receptor (ER), progesterone receptor (PR), and HER2 status.

Specifically, the recommendations, which were published in the Journal of Clinical Oncology, state that beyond ER/PR and HER2 status, results from Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 have clinical utility in guiding treatment decisions on adjuvant therapy in subgroups of patients with breast cancer.

“In the era of precision medicine, the role of biomarkers in guiding clinical care is greater than in the past. An extensive number of new tests have come out in the last 5 to 10 years, but not all have sufficient evidence of clinical utility,” said Lyndsay N. Harris, MD, co-chair of the ASCO expert panel that developed the guideline, in a statement. “These latest recommendations truly inform physicians about which tests need to be performed. But this is not all that goes into patient care. Doctors need to continue discussions with patients to develop individualized treatment plans.”

Additionally, no biomarker test, except for ER/PR and HER2 status, was recommended for use to guide choices of specific drugs or treatment regimens.

Treatment decisions should also consider disease stage, comorbidities, and patient preferences, the authors state in the guideline.

The multidisciplinary panel of experts who developed the recommendations conducted a systematic review of literature published from January 2006 to September 2015, identifying 50 relevant studies. They sought to answer 2 clinical questions:
  1. For women with early-stage invasive breast cancer and with known ER/ PR and HER2 status, which additional biomarkers have demonstrated clinical utility to guide decisions with regard to the need for adjuvant systemic therapy?
  2. Which biomarkers guide the choice of specific drugs or regimens for adjuvant systemic therapy?
For patients who are ER/PR-positive, HER2-negative with node-negative disease, clinicians can use the 21-gene recurrence score Oncotype DX, the 12-gene risk score EndoPredict, the PAM50 risk of recurrence score in conjunction with other clinicopathologic variables, Breast Cancer Index, or urokinase plasminogen activator and plasminogen activator inhibitor type 1 to determine if adjuvant systemic therapy will be useful.

Patients who are HER2-positive or have triple-negative breast cancer (TNBC), however, should not use any of the reviewed assays—Oncotype DX, EndoPredict, MammaPrint, PAM50 risk of recurrence score, Breast Cancer Index, Mammostrat, Immunohistochemistry 4, and urokinase plasminogen activator and plasminogen activator inhibitor type 1—to guide decisions on adjuvant systemic therapy.

None of the specific biomarkers—aside from ER, PR, and HER2—were found to demonstrate strong enough evidence to select patients for adjuvant endocrine therapy selection, the report states. These include CYP2D6 polymorphisms, p27 expression, MKI67 gene, TOP2A gene amplification or TOP2A protein expression, CEP17 duplication, TIMP-1, FoxP3, p53, or PTEN.

In addition, the guideline states that clinicians should not use circulating tumor cells to guide decisions on adjuvant systemic therapy. Tumor-infiltrating lymphocytes should also not be used to guide treatment decisions in patients who are ER/PR-positive, HER2-negative (node-positive or node-negative), HER2-positive, or TNBC.

BRCA1/2 germline mutations were not considered for the guideline, as there is no direct application to choice of adjuvant therapy at this time, the authors noted.

New biomarker tests must be shown to contribute clinically useful information beyond what is already provided by clinical or pathologic indicators in standard use, the authors wrote, unless a new test can provide equivalent information at lower cost, less invasively, or with less inconvenience or risk.

“Research is needed in all areas in the guideline to continue to refine and redefine clinical utility of specific biomarkers. Inclusion of biomarker investigations at the beginning of clinical trials during conception and design and prospective or prospective-retrospective studies that validate the clinical utility of biomarker candidates are important to allow selection of therapy for early-stage invasive breast cancer,” the authors note.


Harris LN, Ismaila N, McShane LM, et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline [published online February 8, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.65.2289.



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