ASCO Releases Clinical Practical Guidelines for Decisions on Systemic Therapy for Metastatic Breast Cancer

The American Society of Clinical Oncology (ASCO)’s Breast Cancer Guideline Advisory Group and Clinical Practice Guideline Committee have published an updated guideline in the Journal of Clinical Oncology on using breast cancer biomarkers to guide clinical decisions on the use of systemic therapy for advanced metastatic breast cancer. The guideline purports to answer the following questions to help physicians decide on initiating systemic therapy or changing an existing treatment regimen:

1. Should metastases be biopsied or otherwise sampled to test for changes from the primary tumor with respect to ER, PR, or HER2 status
2. For women with metastatic breast cancer and with known ER, PR, and HER2 status, which additional tumor markers have demonstrated clinical utility to initiate systemic therapy or direct selection of a new systemic therapy regimen?
3. For women with metastatic breast cancer and with known ER, PR, and HER2 status, which additional tumor markers have demonstrated clinical utility to guide decisions on switching to a different drug or regimen or discontinuing treatment?
4. For biomarkers shown to have clinical utility to guide decisions on systemic therapy for metastatic disease, what are the appropriate assays, timing, and frequency of measurement?

A panel of experts conducted an exhaustive literature review to come up with the following recommendations for the above queries:

1. Biopsy

Patients with accessible, newly diagnosed metastases from primary breast cancer should be offered biopsy for confirmation of disease process and testing of ER, PR, and HER2 status. Patients should be informed that in case of a discordance, there is no evidence to determine whether outcomes are better with treatment regimens based on receptor status in the metastases or the primary tumor. With discordance of results between primary and metastatic tissues, the Panel recommends using the ER, PR, and HER2 status from the metastasis to direct therapy, if supported by the clinical scenario and the patient's goals for care.

2. Systemic therapy

Clinical evaluation, judgment, and patient preferences should guide decisions on initiating systemic therapy for metastatic breast cancer. There is no evidence at this time that initiating therapy solely on the basis of biomarker results beyond those of ER, PR, and HER2 improves health outcomes.

3. Switching therapy based on tissue biomarkers or circulating tumor markers

In patients already receiving systemic therapy for metastatic breast cancer, decisions on changing to a new drug or regimen or discontinuing treatment should be based on clinical evaluation, judgment of disease progression or response, and the patient's goals for care. There is no evidence at this time that changing therapy based solely on biomarker results beyond ER, PR, and HER2 improves health outcomes, quality of life, or cost effectiveness.

4. Clinical utility of existing biomarkers

CEA, CA 15-3, and CA 27-29 may be used as adjunctive assessments to contribute to decisions regarding therapy for metastatic breast cancer. Data are insufficient to recommend use of CEA, CA 15-3, and CA 27-29 alone for monitoring response to treatment. The recommendation for use is based on clinical experience and Panel informal consensus in the absence of studies designed to evaluate the clinical utility of the markers. As such, it is also reasonable for clinicians to not use these markers as adjunctive assessments.

The Panel underscored the importance of continuing research in the field of biomarkers to guide treatment decisions, stating that the study of biomarkers has always lagged behind drug development. However, increased funding of biomarker research by the National Cancer Institute, and the investment by the pharmaceutical industry in developing companion diagnostics is changing the scenario.