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-27

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

adjuvant chemotherapy in breast cancer with 0 to 3 positive nodes.

247

The findings from this trial will help determine the prognostic value of

MammaPrint and the benefit of treating intermediate-risk patients with

adjuvant chemotherapy.

Axillary Lymph Node-Negative Tumors

Small tumors (up to 0.5 cm in greatest diameter) that do not involve the

lymph nodes are so favorable that adjuvant systemic therapy is of

minimal incremental benefit and is not recommended as treatment of

the invasive breast cancer. Endocrine therapy may be considered to

reduce the risk for a second contralateral breast cancer, especially in

those with ER-positive disease. The NSABP database demonstrated a

correlation between the ER status of a new contralateral breast tumor

and the original primary tumor, which reinforced the notion that

endocrine therapy is not an effective strategy to reduce the risk for

contralateral breast cancer in patients diagnosed with ER-negative

tumors.

250

Patients with invasive ductal or lobular tumors 0.6 to 1 cm in

diameter and no lymph node involvement may be divided into patients

with a low risk of recurrence and those with unfavorable prognostic

features that warrant consideration of adjuvant therapy. Unfavorable

prognostic features include intramammary angiolymphatic invasion,

high nuclear grade, high histologic grade, HER2-positive status, or

hormone receptor-negative status (category 2B). The use of endocrine

therapy and chemotherapy in these relatively lower risk subsets of

women must be based on balancing the expected absolute risk

reduction and the individual patient’s willingness to experience toxicity

to achieve that incremental risk reduction.

Patients with lymph node involvement or with tumors greater than 1 cm

in diameter are appropriate candidates for adjuvant systemic therapy

(category 1). For women with lymph node-negative, hormone

receptor-negative tumors greater than 1 cm in diameter, chemotherapy

is recommended (category 1). For those with lymph node-negative,

hormone receptor-positive breast cancer tumors greater than 1 cm,

endocrine therapy with chemotherapy is recommended (category 1).

Incremental benefit of combination chemotherapy in patients with lymph

node-negative, hormone receptor-positive breast cancer may be

relatively small.

251

Therefore, the panel recommends that tumor

hormone receptor status be included as one of the factors considered

when making chemotherapy-related treatment decisions for patients

with node-negative, hormone receptor-positive breast cancer. Patients

for whom this evaluation may be especially important are those with

tumors characterized as 0.6 to 1.0 cm and hormone receptor-positive

that are grade 2 or 3 or have unfavorable features, or tumors greater

than 1 cm and hormone receptor-positive and HER2-negative.

However, chemotherapy should not be withheld from these patients

solely based on ER-positive tumor status.

3,251,252

The use of genomic/gene expression array data that also incorporate

additional prognostic/predictive biomarkers (eg, Oncotype DX

recurrence score) may provide additional prognostic and predictive

information beyond anatomic staging and determination of ER/PR and

HER2 status. Assessment of the role of the genomic/gene expression

array technology is difficult because of the retrospective nature of the

studies, the evolution of chemotherapy and hormone therapy regimens,

and the overall more favorable prognosis of the patients with lymph

node-negative disease compared with those enrolled in the historically

controlled clinical trials. Some NCCN Member Institutions consider

performing RT-PCR analysis (eg, Oncotype DX assay) to further refine

risk stratification for adjuvant chemotherapy for patients with

node-negative, ER-positive, HER2-negative breast cancers >0.5 cm,

whereas others do not.