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ASCO: Biomarker assays demonstrate utility for early-stage invasive breast cancer
ASCO has issued a new clinical practice guideline that endorses the use of several biomarker assays to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer and known hormone receptor and HER-2 status.
However, the guidance states no biomarker test other than ER, PR and HER-2 should be used to make choices of specific drugs or treatment regimens.
“In the era of precision medicine, the role of biomarkers in guiding clinical care is greater than in the past,” Lyndsay N. Harris, MD, professor of medicine, director of the breast cancer program, and Diana Hyland Chair in Breast Cancer at Case Western Reserve University School of Medicine — as well as co-chair of the ASCO expert panel that developed the guideline — said in a press release. “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.”
To provide recommendations on appropriate use of biomarker assays, Harris and colleagues performed a literature search of systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies and observational studies conducted between 2006 and 2014.
The researchers considered OS, DFS and RFS to be outcomes of interest in these studies. Informal consensus served as the primary tool for developing evidence-based recommendations.
Harris and colleagues identified 50 relevant studies, 19 of which (prospective-retrospective, n = 18; randomized controlled trial, n = 1) evaluated the clinical utility of biomarker assay use for determining adjuvant systemic therapy.
Based on the available data, the expert panel endorsed the use of Oncotype DX (Genomic Health), EndoPredict (Sividon Diagnostics), PAM50 (Prosigna, NanoString Technologies), Breast Cancer Index (Bio Theranostics), and the urokinase plasminogen activator and plasminogen activator inhibitor type 1 assay as tools for the guidance of adjuvant systemic therapy.
However, none of the studies were found to guide choice of specific treatments or regimens. Thus, the expert panel judged that no biomarker test — aside from those for ER, PR and HER-2 status — should be used to choose specific drugs or regimens. They also stressed that treatment decisions should consider disease stage, comorbidities and patient preferences.
The expert panel acknowledged the lack of prospective confirmatory trials and the lack of data on clinical utility and reproducibility of assays as limitations of their recommendations.
They further noted that additional research remains necessary in all areas to refine and redefine clinical biomarker utility.
“These latest recommendations truly inform physicians about which tests need to be performed,” Harris said. “But this is not all that goes into patient care. Doctors need to continue discussions with patients to develop individualized treatment plans.” – by Cameron Kelsall
Disclosure: Harris reports research funding from Philips Research. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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The ASCO Breast Cancer Guidelines Advisory Group and the Clinical Practice Guideline Committee has issued new recommendations for biomarker use in early-stage breast cancer. The recommendations update a previous guideline published in 2007 and illustrate both progress in this field and refinements in the guideline development process.
Compared with the previous version, the new recommendations are more focused. They target a specific clinical niche — adjuvant therapy for stage I to stage III breast cancer — and specific assays are assessed by taking into consideration the evidence that supports the analytical validity, clinical validity and clinical utility of the tests. The task force made separate recommendations for the three clinically important breast cancer subtypes (ER-positive, triple-negative breast cancer and HER-2–positive).
The guideline endorses the use of the Oncotype Dx (Genomic Health), EndoPredict (Sividon Diagnostics), PAM50 (Prosigna, NanoString Technologies) and Breast Cancer Index assays for ER-positive cancers to select patients for adjuvant chemotherapy. These tests are not recommended for triple-negative breast cancer or HER-2–positive cancers because evidence for clinical validity and utility is limited or nonexistent.
These recommendations mostly reflect already existing current practice. The National Comprehensive Cancer Network and the European St. Gallen treatment guidelines have already endorsed the use of many of these assays several years ago. The St. Gallen guideline also includes MammaPrint (Agendia) — which is an FDA-cleared assay in the U.S. — and takes a more liberal attitude toward using Ki67 immunohistochemistry as an additional acceptable option for prognostic risk stratification of ER-positive cancers. The ASCO guideline development panel has done an excellent job to succinctly convey the type and quality of evidence that supports a particular recommendation, which is further qualified by levels of strength.
However, the language of the actual recommendations is rather strong and dichotomous and either state that “the clinician may use” or “the clinician should not use” an assay. Although this provides practical clarity, it does not do full justice for the available evidence for some uses of these tests.
The recommendation that the above tests should not be used in triple-negative breast cancer is based on consistent and broad evidence that demonstrated no clinically meaningful risk stratification function in this disease subtype. On the other hand, the recommendation that these tests should not be used in patients with one or two positive nodes is based on well-reasoned caution, despite multiple studies independently demonstrating continued prognostic function for each of the tests even in node-positive patients, some of which even provide nodal status-adjusted risk estimates.
Similarly, the guideline recommends against using any of the tests to guide selection of extended adjuvant therapy, despite multiple publications supporting their ability to predict late recurrences. In the case of at last one assay, there are data to suggest that those at high risk for late recurrence also benefit from extended endocrine therapy. Practicing oncologists often encounter clinical scenarios when test results with some degree of uncertainty still provide helpful information.
Maybe future iterations of guidelines could consider three tiered recommendations — definitely recommended, definitely not recommended and maybe considered in some scenarios.