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-19

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

pertuzumab, trastuzumab, and docetaxel. pCR is defined by the FDA as

“the absence of invasive cancer in the breast and lymph nodes.”

In the NeoSphere trial, 417 patients were randomized 1:1:1:1 to receive

trastuzumab plus docetaxel, or pertuzumab and trastuzumab plus

docetaxel, or pertuzumab and trastuzumab, or pertuzumab plus

docetaxel. Forty-five point eight percent [95% CI, 36.1–55.7] of patients

who received pertuzumab plus trastuzumab and docetaxel achieved

pCR, compared with only 29% [CI, 20.6–38.5] of patients who achieved

pCR on the trastuzumab plus docetaxel regimen (

= .0063).

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The

TRYPHAENA was a phase II, randomized, multicenter trial designed to

evaluate the safety and tolerability of trastuzumab and pertuzumab in

combination with anthracycline-, or carboplatin-based neoadjuvant

chemotherapy. A total of 225 patients with HER2-positive, locally

advanced (T2-3, N2-3, M0; T4a-c, any N,M0), inflammatory (T4d, any

N,M0), or early-stage breast cancer (tumors >2 cm) were enrolled and

randomized 1:1:1 to receive 6 cycles of neoadjuvant therapy with FEC

plus trastuzumab and pertuzumab followed by docetaxel, trastuzumab,

and pertuzumab; or FEC followed by docetaxel, trastuzumab, and

pertuzumab; or docetaxel, carboplatin, and trastuzumab along with

pertuzumab. Based on the assessment of pCR, all 3 regimens seem

active. The reported pCR ranged from 57.3% to 66.2%. The highest

pCR was observed in patients who received pertuzumab, trastuzumab,

docetaxel, and carboplatin chemotherapy, with a pCR of 66.2%. The

adverse events reported in the trial were consistent with what was

observed which each of the three agents, and low rates of symptomatic

left ventricular systolic dysfunction were reported.

The NCCN Panel has included pertuzumab-based regimens as

neoadjuvant therapy options for patients with early-stage (≥T2 or ≥N1),

HER2-positive tumors.

Several randomized trials have assessed the value of neoadjuvant

endocrine therapy in postmenopausal women with ER-positive breast

cancer. These studies have generally compared the rates of objective

response and rates of breast-conserving surgery among treatment with

tamoxifen, anastrozole, anastrozole plus tamoxifen, or letrozole. These

studies consistently demonstrate that the use of either anastrozole or

letrozole alone provides superior rates of breast-conserving surgery and

usually objective response when compared with tamoxifen.

170,171

Based

on these trials, if preoperative endocrine therapy is to be utilized, an

aromatase inhibitor is preferred in the treatment of postmenopausal

women with hormone receptor-positive disease.

Local therapy following a complete or partial response to preoperative

systemic therapy is usually lumpectomy if possible along with surgical

axillary staging. If lumpectomy is not possible or progressive disease is

confirmed, mastectomy is performed along with surgical axillary staging

with or without breast reconstruction. Surgical axillary staging may

include SLN biopsy or level I/II dissection. If SLN biopsy was performed

before administering preoperative systemic therapy and the findings

were negative, then further ALN staging is not necessary. If an SLN

procedure was performed before administering preoperative systemic

therapy and the findings were positive, then a level I/II ALN dissection

should be performed.

If an inoperable tumor fails to respond, or if the response is minimal,

after several cycles of preoperative systemic therapy, or the disease

progresses at any point, an alternative chemotherapy regimen and/or

preoperative radiation therapy should be considered followed by local

therapy, usually a mastectomy plus axillary dissection, with or without

breast reconstruction.