NCCN VERSION 2 2015

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NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

tamoxifen. Those with one or two variant alleles with either reduced

or no activity are designated as intermediate metabolizers and poor

metabolizers, respectively.

A large retrospective study of 1325 patients

found that time to disease recurrence was significantly shortened in

poor metabolizers of tamoxifen.

314

However, the BIG 1-98 trial reported

on the outcome based on CYP2D6 genotype in a subset of

postmenopausal patients with endocrine-responsive, early invasive

breast cancer.

315

The study found no correlation between CYP2D6

allelic status and disease outcome or between CYP2D6 allelic status

and tamoxifen-related adverse effects.

315

A genetic analysis of the

ATAC trial found no association between CYP2D6 genotype and clinical

outcomes.

316

Given the limited and conflicting evidence at this time,

317

the NCCN Breast Cancer Panel does not recommend CYP2D6 testing

as a tool to determine the optimal adjuvant endocrine strategy. This

recommendation is consistent with the ASCO Guidelines.

318

When

prescribing a selective serotonin reuptake inhibitor (SSRI), it is

reasonable to avoid potent and intermediate CYP2D6 inhibiting agents,

particularly paroxetine and fluoxetine, if an appropriate alternative

exists.

Adjuvant Cytotoxic Chemotherapy

Several combination chemotherapy regimens are appropriate to

consider when adjuvant cytotoxic chemotherapy is utilized. All adjuvant

chemotherapy regimens listed in the NCCN Guidelines have been

evaluated in phase III clinical trials, and the current version of the

adjuvant chemotherapy guidelines does not distinguish between options

for chemotherapy regimens by ALN status.

The adjuvant chemotherapy guidelines also include specific

representative doses and schedules for the recommended adjuvant

chemotherapy regimens. The regimens have been categorized as

“preferred” or “other.”

The purpose of distinguishing the adjuvant chemotherapy regimens as

preferred and other adjuvant chemotherapy regimens is to convey the

sense of the panel regarding the relative efficacy and toxicity of the

regimens.

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Factors considered by the panel include the efficacy,

toxicity, and treatment schedules of the regimens. Summarized below

are clinical trial results focusing on treatment efficacy.

Preferred Regimens

Regimens listed as preferred include: dose-dense doxorubicin and

cyclophosphamide (AC) with dose-dense sequential paclitaxel;

dose-dense AC followed by sequential weekly paclitaxel; and docetaxel

plus cyclophosphamide (TC).

The results of two randomized trials comparing AC chemotherapy with

or without sequential paclitaxel chemotherapy in women with axillary

node-positive breast cancer suggest improved disease-free rates, and

results from one of the trials showed an improvement in OS, with the

addition of paclitaxel.

320,321

On retrospective analysis, the apparent

advantage of the paclitaxel-containing regimen appears greater in

women with ER-negative breast cancers.

A randomized trial evaluated the use of concurrent versus sequential

chemotherapy (doxorubicin followed by paclitaxel followed by

cyclophosphamide vs. doxorubicin plus cyclophosphamide followed by

paclitaxel) given either every 2 weeks with filgrastim support or every 3

weeks. The results show no significant difference between the two

chemotherapy regimens, but demonstrate a 26% reduction in hazard of

recurrence (

= .01) and a 31% reduction in the hazard of death (

.013) for the dose-dense regimens.

322

The ECOG E1199 study was a four-arm trial that randomized 4950

women to receive AC chemotherapy followed by either paclitaxel or