NCCN VERSION 2 2015

NCCN Guidelines Version 2.2015 Breast Cancer

NCCN Guidelines Index Breast Cancer Table of Contents Discussion

methods (including MammaPrint and Oncotype DX) provided similar predictions of clinical outcome. 236 A similar approach has been used to define more limited sets of genes for prognostic and predictive purposes. 237 For example, the MammaPrint assay uses microarray technology to analyze a 70-gene expression profile from breast tumor tissue as a means of selecting patients with early-stage breast cancer who are more likely to develop distant metastases. 238-244 MammaPrint is approved by the FDA to assist in assignment of women with ER-positive or ER-negative breast cancer into a high versus low risk for recurrence, but not for predicting benefit from adjuvant systemic therapy. Studies using MammaPrint as a prognostic and predictive tool are small and/or retrospective in nature. Multiple other multi-gene or multi-gene expression assay systems have been developed. These systems are generally based upon small, retrospective studies, and the Panel believes that none are currently sufficiently validated to warrant inclusion in the guideline. While many of the DNA microarray technologies are able to stratify patients into prognostic and/or predictive subsets on retrospective analysis, the gene subsets differ from study to study, and prospective clinical trials testing the utility of these techniques have yet to be reported. Currently, prospective randomized clinical trials are addressing the use of Oncotype DX and MammaPrint as predictive and/or prognostic tools in populations of women with early-stage, lymph node-negative breast cancer. 245-247 Pending the results of the prospective trials, the panel considers the 21-gene RT-PCR assay an option when evaluating patients with primary tumors characterized as 0.6 to 1.0 cm with unfavorable features or >1 cm, and node-negative, hormone receptor-positive, and HER2-negative (category 2A). In this circumstance, the recurrence score may be determined to assist in

estimating likelihood of recurrence and benefit from chemotherapy. The panel emphasizes that the recurrence score should be used for decision-making only in the context of other elements of risk stratification for an individual patient. Unplanned, retrospective subset analysis from a single randomized clinical trial in post-menopausal, ALN-positive, ER-positive breast cancer found that the 21-gene RT-PCR assay may provide predictive information for chemotherapy benefit in addition to tamoxifen. 248 Patients with a high score in the study benefited from chemotherapy, whereas patients with a low score did not appear to benefit from the addition of chemotherapy regardless of the number of positive lymph nodes. 248 Patient selection for assay use remains controversial. The additional benefit from adjuvant chemotherapy in addition to endocrine therapy is currently unclear for intermediate-risk patients (as assessed by the gene-based assays). The TAILORx and RxPONDER trials are being conducted to help answer this question. In the TAILORx trial, patients with node-negative, hormone receptor-positive breast cancer classified as being at low risk based on the gene signature or Adjuvant! Online are receiving endocrine therapy alone, whereas patients deemed to be at high risk based on gene signature profiles or other characteristics are receiving chemotherapy in addition to endocrine therapy. Those classified with an intermediate risk are being randomized to receive chemotherapy or no chemotherapy. 249 The RxPONDER trial will confirm the SWOG-8814 trial data for women with ER-positive, node-positive disease treated with endocrine therapy with or without chemotherapy based on risk scores. 245 The findings from these trials will help determine the benefit of treating patients at intermediate risk with adjuvant chemotherapy. The MINDACT trial is underway in Europe to compare the 70-gene signature with the commonly used clinicopathologic criteria in selecting patients for

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