As summarized in this issue of The ASCO Post (see "ASCO Clinical Practice Guideline: Use of Biomarkers to Guide Systemic Therapy for Women With Metastatic Breast Cancer"), Van Poznak and colleagues recently presented an ASCO clinical practice guideline on the use of biomarkers for decisions regarding systemic therapy in women with metastatic breast cancer.¹ A previous ASCO biomarker guideline addressed all indications in breast cancer for biomarker assays.² Later, ASCO and the College of American Pathologists updated two guidelines on testing for human epidermal growth factor receptor 2 (HER2) and endocrine receptors for estrogen and progesterone.^3-5

Van Poznak et al addressed the use of biomarkers in selecting treatment for metastatic breast cancer on the basis of estrogen receptor, progesterone receptor, and HER2 status, as well as considering evaluation of response to therapy using assays for carcinoembryonic antigen, cancer antigen 15-3 (CA 15-3), cancer antigen 27-29 (CA 27-29), and circulating tumor cells. The lack of controlled data and the variability in clinical practice in these areas almost certainly explain the high priority ASCO assigned to this project. The guidelines also re-emphasize the importance of distinguishing the predictive vs prognostic value of clinical information.

Clinical Context and Biomarker Results

The guidelines recommend biopsy of a site of disease if accessible at the time of first relapse. This step serves to affirm the diagnosis conclusively and allows retesting of estrogen receptor, progesterone receptor, and HER2 status. Most trials test treatment for selected patients with metastatic disease on the basis of estrogen receptor, progesterone receptor, and HER2 testing of the primary tumor.

When biomarkers of the metastatic disease differ from those of the primary tumor, it is unknown which tumor biomarker profile will best predict the most effective approach to treatment. Retesting metastatic tumor is especially attractive when the primary tumor is negative for endocrine or HER2 biomarkers, and retesting checks the accuracy of the initial assays. However, in the situation in which tests of the metastatic site are negative for biomarkers and positive in the primary tumor, extra caution must be taken.

For both situations, the guideline committee sagely advises that treatment decisions must be informed by the clinical context as well as biomarker results. For example, an endocrine approach should be selected for an elderly woman relapsing in bone 10 years after diagnosis with an estrogen receptor/progesterone receptor–positive primary tumor regardless of repeat biomarker results. Thus, the guidelines acknowledge that no reexamination of biomarkers of the primary tumor can be an acceptable practice.

Assessing Treatment Efficacy

The guidelines also address the use of biomarkers to gauge the efficacy of therapy. Again, the guidelines allow that markers may be used with clinical information and patient preference to determine the need for change in treatment but expressly warn against changing therapy based on biomarkers alone.

Some would argue that there is no role for biomarkers in assessing treatment efficacy, but others use the biomarker trend to support clinical judgment in patients who have signs, symptoms, and tumor imaging that may be difficult to interpret or when marker trends may decrease costly and uncomfortable imaging. The measurement of persistent circulating tumor cells after some therapy was acknowledged to be prognostic of poorer outcome when compared with patients in whom circulating tumor cells became undetectable, but persistent circulating tumor cells did not predict that a change in therapy improved outcome, and the use of circulating tumor cells was not ­endorsed.

The committee should be commended for gleaning the data from a limited number of trials and lending its great clinical experience to publish guidelines that enlighten the often mysterious art of managing metastatic breast cancer. ■

Disclosure: Dr. Reed reported no potential conflicts of interest.

References

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.

2. Harris L, Fritsche H, Mennel R, et al: American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 25:5287-5312, 2007.

3. 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. J Clin Oncol 25:118-145, 2007.

4. Wolff AC, Hammond ME, Hicks DG, et al: Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31:3997-4013, 2013.

5. Hammond ME, Hayes DF, Dowsett M, et al: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784-2795, 2010.