As reported in the Journal of Clinical Oncology by Catherine Van Poznak, MD, and colleagues, ASCO has issued a clinical practice guideline on the use of biomarkers to guide decisions on systemic therapy in women with metastatic breast cancer.¹ The statement is based on an ASCO expert panel review of systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies reported between 2006 and September 2014. The panel was co-chaired by ­Lyndsay N. Harris, MD, of Seidman Cancer Center, Case Western Reserve University, Cleveland, and Dr. Van Poznak, of the University of Michigan Comprehensive Cancer Center, Ann Arbor.

Guideline Questions

The expert panel sought to develop answers to the following questions:

(1) Should metastases be biopsied or otherwise sampled to test for changes from the primary tumor with respect to estrogen receptor, progesterone receptor, or HER2 status?

(2) For women with metastatic breast cancer and known estrogen receptor, progesterone receptor, 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 known estrogen receptor, progesterone receptor, 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 in questions 2 and 3, what are the appropriate assays, timing, and frequency of measurement?

Key Points

The key points of the guideline are reproduced below, with the type of recommendation, evidence quality, and strength of recommendation shown in parentheses.

Patients with accessible, newly diagnosed metastases from primary breast cancer should be offered biopsy for confirmation of disease process and testing of estrogen receptor, progesterone receptor, and HER2 status. They should also be informed that if discordances are found, evidence is lacking 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 consensus is to preferentially use the estrogen receptor, progesterone receptor, and HER2 status from the metastasis to direct therapy, if supported by the clinical scenario and the patient’s goals for care. (Type: evidence-based for biomarker change from primary to metastasis, but no evidence to address systemic therapy choices affecting health outcome when biomarker change occurs. Evidence quality: insufficient. Strength of recommendation: moderate.)

Decisions on initiating systemic therapy for metastatic breast cancer should be based on clinical evaluation, judgment, and patient preferences. There is no evidence at this time that initiating therapy solely on the basis of biomarker results beyond those of estrogen receptor, progesterone receptor, and HER2 improves health outcomes. (Type: evidence-based. Evidence quality: low. Strength of recommendation: moderate.)

Recommendations for tissue biomarkers: 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 estrogen receptor, progesterone receptor, and HER2 improves health outcomes, quality of life, or cost-effectiveness. (Type: evidence-based. Evidence quality: low. Strength of recommendation: moderate.)

Recommendations for 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 circulating biomarker results improves health outcomes, quality of life, or cost-effectiveness. (Type: evidence-based. ­Evidence quality: intermediate. Strength of recommendation: moderate.)

Carcinoembryonic antigen (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 not to use these markers as adjunctive assessments. (Type: informal consensus. Evidence quality: insufficient. Strength of recommendation: moderate.) ■

Disclosure: Dr. Van Poznak has received research funding from Amgen and Novartis (via her institution) and has reported patents, royalties, or other intellectual property associated with UpToDate. For full disclosures of the other authors, visit jco.ascopubs.org.

Reference

1. Van Poznak C, Somerfield MR, Bast RC, et al: Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 33:2695-2704, 2015.