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-17

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

and placement of image-detectable marker(s) should be considered to

demarcate

the tumor bed for any future (post-chemotherapy) surgical

management. Clinically positive ALN should be sampled by FNA or core

biopsy and the positive nodes must be removed following preoperative

systemic therapy at the time of definitive operation. Patients with

clinically negative ALNs should have axillary ultrasound prior to

neoadjuvant treatment. For those with clinically suspicious ALNs, the

panel recommends consideration of either a core biopsy or FNA of

these nodes.

152

. If FNA or core biopsy indicates any positive nodes,

these should be removed following neoadjuvant therapy at the time of

definitive surgery.

According to the NCCN Panel, axillary staging after preoperative

systemic therapy may include sentinel node biopsy or level I/II

dissection. Level I/II dissection should be done when patients are

proven node positive prior to neoadjuvant therapy (category 2B). The

false-negative rate of SLN biopsy in either the pre- or

post-chemotherapy settings is low.

132,153,154

Nevertheless, the possibility

remains that a pathologic complete response (pCR) following

chemotherapy may occur in lymph node metastases previously

undetected by clinical exam. An SLN excision can be considered before

administering preoperative systemic therapy, because it provides

additional information to guide local and systemic treatment

decisions.

155,156

In the event that SLN resection is performed after

administration of preoperative systemic therapy, both the

pre-chemotherapy clinical and the post-chemotherapy pathologic nodal

stages must be used to determine the risk of local recurrence. Close

communication between members of the multidisciplinary team,

including the pathologist, is particularly important when any treatment

strategy involving preoperative systemic therapy is planned.

In some patients, preoperative systemic therapy results in sufficient

tumor response that makes breast-conserving therapy possible.

Because complete or near-complete clinical responses are common,

the use of percutaneously placed clips into the breast under

mammographic or ultrasound guidance or other method of localizing

pre-chemotherapy tumor volume aids in the post-chemotherapy

resection of the original area of tumor and is encouraged. The results of

the NSABP B-18 trial show that breast conservation rates are higher

after preoperative systemic therapy.

157

However, preoperative systemic

therapy has no demonstrated disease-specific survival advantage over

postoperative adjuvant chemotherapy in patients with stage II tumors.

NSABP B-27 is a three-arm, randomized, phase III trial of women with

invasive breast cancer treated with preoperative systemic therapy with

AC (doxorubicin/cyclophosphamide) for 4 cycles followed by local

therapy alone, preoperative AC followed by preoperative docetaxel for 4

cycles followed by local therapy, or AC followed by local therapy

followed by 4 cycles of postoperative docetaxel. Results from this study,

which involved 2411 women, documented a higher rate of complete

pathologic response at the time of local therapy in patients treated

preoperatively with 4 cycles of AC followed by 4 cycles of docetaxel

versus 4 cycles of preoperative AC. DFS and OS have not been shown

to be superior with the addition of docetaxel treatment in B-27.

158

A DFS

advantage was observed (HR, 0.71; 95% CI, 0.55–0.91;

= .007)

favoring preoperative versus postoperative docetaxel in the subset of

patients experiencing a clinical partial response to AC.

Several chemotherapy regimens have been studied as preoperative

systemic therapy. The panel believes that the regimens recommended

in the adjuvant setting are appropriate to consider in the preoperative

systemic therapy setting. The benefits of “tailoring” preoperative

systemic therapy (ie, switching following limited response) or using