NCCN VERSION 2 2015

The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

MS-26

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

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