Prediction of adjuvant chemotherapy benefit in endocrine responsive, early breast cancer using multigene assays

Abstract

The prediction of adjuvant chemotherapy benefit over and above endocrine therapy using multigene assay-determined risk category differs greatly across risk level and challenges the previous adjuvant therapy paradigm that degree of benefit is the same regardless of risk. These data justify current clinical use of these assays, while ongoing prospective studies will refine their role in practice settings.

The prognostic importance of cathepsin D and E-cadherin in early breast cancer: A single-institution experience

“…Notably, the addition of Ki67 to the model of cathepsin D and E-cadherin in our study did not improve prediction over and above the two-biomarker model. Multiple studies have previously shown that the immunohistochemical expression of nuclear Ki67 may be prognostic and predictive in patients with EBC (22), and the majority of gene expression-based predictors, including Oncotype DX, make use of proliferation phenotypes (23).…”

MammaPrint for Individualized Recurrence Risk Assessment and Treatment Recommendations for Early-Stage Breast Cancer Patients

“…A substantial decrease, from 63% in 2009 to 49% in 2010, in the use of chemotherapy for node-negative breast cancer patients, has seemingly been driven by clinician's use of the two prognostic genomic assays Oncotype Dx and MammaPrint. This corresponds to the determination that, at 10-year follow-up, low-risk patients with node positivity gained absolutely no benefit from chemotherapy with 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC) chemotherapy with or without tamoxifen [61]. Compared to conventional risk assessment tools, microarray data are much more quantitative and reproducible as they are subjected to less human variability.…”

Neoadjuvant Systemic Therapy in Breast Cancer

“…Neither assay has been validated nor demonstrated prognostic utility in hormone receptor-negative breast cancer. Both the 21-gene and 70-gene assays also provide additional information for treatment decision-making beyond algorithms based on standard clinicopathologic criteria such as Adjuvant-Online (Albain et al, 2009). Although the original validation of the 21-gene RS assay established its prognostic ability in patients treated with adjuvant tamoxifen, a recent study demonstrated similar prognostic ability in patients who received an aromatase inhibitor as upfront adjuvant therapy (Dowsett et al, 2008).…”

“…Although the original validation of the 21-gene RS assay established its prognostic ability in patients treated with adjuvant tamoxifen, a recent study demonstrated similar prognostic ability in patients who received an aromatase inhibitor as upfront adjuvant therapy (Dowsett et al, 2008). For both prognosis and prediction, only the 21-gene RS assay has been studied with specimens from phase III adjuvant therapy trials (Albain et al, 2009.…”