The terms prognostic and predictive are frequently used interchangeably; however, there are some important distinctions. Generally speaking, a predictive biomarker identifies patients who would benefit from a specific intervention. things The BRAF V600E mutation, which predicts benefit from tyrosine kinase inhibitor therapy with vemurafinib in metastatic melanoma, is an example of a predictive biomarker.23 A prognostic biomarker provides information on the likely outcome of the disease irrespective of treatment. An example of a prognostic biomarker is the KRAS mutation, which is associated with poor survival in non�Csmall-cell lung cancer.24 Some biomarkers are both predictive and prognostic, such as protein overexpression or gene amplification of HER2, or KRAS mutations in colorectal cancer.

The 3 currently available genomic biomarker assays for breast cancer are not ��predictive�� of chemotherapy benefit in the same sense as BRAF for melanoma because none of these assays were specifically designed to predict which subset of patients would benefit from chemotherapy. The first genomic biomarker assay that became available for breast cancer treatment decisions was the Oncotype DX. This assay was initially tested and validated in women with hormone-receptor-positive early breast cancer who were receiving endocrine therapy. This assay, therefore, gives a recurrence score for patients on endocrine therapy. The gene signatures comprising both PAM50 and MammaPrint, by contrast, were derived from patients with all subtypes of breast cancer.

Moreover, patients in the initial and validation data sets underwent surgery only and did not receive systemic adjuvant therapy.41,28,53 A truly predictive chemotherapy genomic signature for breast cancer would likely be best developed in the neoadjuvant setting correlating signature with pathologic complete response, which is a validated surrogate marker for overall survival. Such predictive biomarkers have been evaluated; however, further elaboration is beyond the scope of this review.25,26 Datasets showing a significant benefit of adjuvant chemotherapy in breast cancer patients with a high recurrence risk score by both Oncotype DX and MammaPrint are predictive in the sense that they quantify the recurrence risk.27,32,48 The relative benefit of chemotherapy can then be extrapolated for each risk group.

26 Oncotype DX Oncotype DX is a multiplex, 21-gene, real time, PCR-based assay that was developed to quantify the likelihood of disease recurrence in women Cilengitide with stages I and II hormone-receptor-positive, lymph-node-negative, invasive breast cancer, and who had received tamoxifen for 5 years.28 This genomic assay was developed through selection of a panel of genes with known function that were thought to be the most relevant to the biology of hormone-receptor breast cancer.