Genomic Tests Guiding the Adjuvant Systemic Therapy in Women with Breast Cancer

Abstract

Introduction: The decision to initiate adjuvant chemotherapy after surgery in patients with estrogen receptor-positive and lymph node-negative early stage breast cancer, has traditionally been guided by clinical and pathological factors (characteristics of the patient and the tumor), in conjunction with the clinician`s and the patient`s preferences. Many of these patients are exposed to adjuvant chemotherapy toxicity and cost with little or no clinical benefit, and identifying those who do benefit, remains a challenge. Gene-expression profiling is an emerging clinical strategy which evaluates cancer recurrence risk by using genomic information in order to support better decision-making about adjuvant chemotherapy. Materials and Methods: In this research we analyzed three types of gene-expression-profiling tests of breast cancer. A multigene immunohistochemistry-based test, known as MammoStrat, classifies breast cancer patients into low-, moderate- or high-risk categories for disease recurrence. The MammaPrint assay is a seventy-gene signature developed using tumor tissue from young women (less than fifty-five years of age) with node-negative disease. OncotypeDX is a twenty-one-gene-expression profiling that provides a probability of recurrence score for women with early stage (Stage I or II), estrogen receptor-positive, node-negative breast cancer, and categorizes patients as low-, intermediate- , or high- risk for distant metastasis in the next five to ten years. Results: A high-risk result is correlated with distant breast cancer recurrence rate, hormone therapy benefit, and chemotherapy benefit. A lower score is correlated with a lower risk of distant breast cancer recurrence, lower benefit of chemotherapy, and greater benefit of hormone therapy. Conclusion: Use of gene-expression profiling along with clinical and pathological classification of early-stage breast cancer provides the physician with additional information about adjuvant systemic therapy in these patients in order to maximize efficacy and minimize adverse side effects.