Use of Multiparameter Tests for Identifying Women with Early Breast Cancer Who Do Not Need Adjuvant Chemotherapy.

Abstract

For women diagnosed with early breast cancer, 3 main forms of adjuvant systemic therapy are available, i.e., endocrine therapy, anti–human epidermal growth factor receptor 2 (HER2)4 therapy, and chemotherapy (Table 1). The decision on whether or not to administer endocrine therapy is based on the estrogen receptor (ER)–progesterone receptor (PR) status of the primary cancer, i.e., ER-positive or PR-positive patients receive endocrine therapy. On the other hand, patients with HER2 gene amplification/overexpression are usually treated with anti-HER2–based chemotherapy, especially trastuzumab (Herceptin). In contrast to the situation with endocrine and anti-HER2–based therapy, predictive biomarkers for selecting patients for specific forms of chemotherapy are currently unavailable. View this table: Table 1. Systemic therapies used to treat breast cancer. Although biomarkers for predicting benefit from specific chemotherapy drugs currently do not exist, several recently described multigene signatures (1) are indirectly predictive of a benefit from adjuvant chemotherapy in general, as they identify women at an increased risk of early recurrence. Because of this enhanced risk of early recurrence, these women tend to obtain a greater absolute reduction in recurrence and death rates from treatment with adjuvant chemotherapy. Furthermore, some of these multigene signatures (e.g., Oncotype DX) may be predictive of a benefit from chemotherapy since they measure the expression of genes involved in cell proliferation. Enhanced cancer cell proliferation is generally associated with a better response to cytotoxic drugs. In a recent report, Cardoso et al. (2) described the clinical validation of one of these multigene signatures, named the 70-gene signature or MammaPrint, using a prospective randomized trial, i.e., a level I evidence study. In this phase 3 study, which involved 6693 women with newly diagnosed invasive breast cancer with 0–3 metastatic lymph nodes [Microarray for Node-Negative Disease Avoids Chemotherapy (MINDACT) trial], women were categorized as having a low or high risk of disease recurrence using 2 …