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-35

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

docetaxel given by either an every-3-week schedule or a weekly

schedule.

323-325

At a median 63.8 months of follow-up, no statistically

significant differences in DFS or OS were observed when comparing

paclitaxel to docetaxel or weekly versus every-3-week administration. In

a secondary series of comparisons, weekly paclitaxel was superior to

every-3-week paclitaxel in DFS (HR, 1.27; 95% CI, 1.03– 1.57;

.006) and OS (HR, 1.32; 95% CI, 1.02–1.72;

= .01), and

every-3-week docetaxel was superior to every-3-week paclitaxel in DFS

(HR, 1.23; 95% CI, 1.00–1.52;

= .02) but not in OS.

325

Based on

these results, as well as the findings from the CALGB trial 9741 that

showed dose-dense AC followed by paclitaxel every 2 weeks to have a

survival benefit when compared with the regimen of AC followed by

every-3-week paclitaxel,

322

the every-3-week paclitaxel regimen has

been removed from the guidelines.

Combination TC was compared with AC chemotherapy in a trial that

randomized 1016 women with stage I to III breast cancer.

326

At a

median follow-up of 7 years, overall DFS (81% vs. 75%; HR, 0.74; 95%

CI, 0.56–0.98;

= .033) and OS (87% vs. 82%; HR, 0.69; 95% CI,

0.50–0.97;

= .032) were significantly improved with TC compared with

AC.

Other Regimens

Other regimens included in the guidelines are: AC; fluorouracil,

doxorubicin, and cyclophosphamide (FAC/CAF); cyclophosphamide,

epirubicin, and fluorouracil (FEC/CEF); epirubicin and

cyclophosphamide (EC); CMF; AC with sequential docetaxel

administered every 3 weeks; AC with sequential weekly paclitaxel;

FEC/CEF followed by docetaxel or weekly paclitaxel; FAC followed by

weekly paclitaxel; and docetaxel, doxorubicin, and cyclophosphamide

(TAC).

The AC regimen for four cycles has been studied in randomized trials,

resulting in relapse-free survival and OS equivalent to CMF

chemotherapy.

327-329

No benefit from dose escalation of either

doxorubicin or cyclophosphamide was shown.

320,330

Studies of CMF chemotherapy versus no chemotherapy have shown

DFS and OS advantages with CMF chemotherapy.

3,331

Studies using

CAF/FAC chemotherapy have shown that the use of full-dose

chemotherapy regimens is important.

332

In the

EBCTCG

overview of

polychemotherapy, comparison of anthracycline-containing regimens

with CMF showed a 12% further reduction in the annual odds of

recurrence (

= .006) and an 11% further reduction in the annual odds

of death (

= .02) with anthracycline-containing regimens.

331

Based on

these data, the Panel qualified the appropriate chemotherapy regimens

by the statement that anthracycline-containing regimens are preferred

for node-positive patients.

The

EBCTCG

analysis, however, did not consider the potential

interaction between HER2 tumor status and efficacy of

anthracycline-containing versus CMF chemotherapy regimens.

Retrospective analysis has suggested that the superiority of

anthracycline-containing chemotherapy may be limited to the treatment

of those breast cancers that are HER2

positive.

214,216,219,259,333-335

The

retrospective finding across several clinical trials that

anthracycline-based chemotherapy may be more efficacious in patients

whose tumors are HER2

positive has led to a footnote stating that

anthracycline-based chemotherapy may be superior to

non-anthracycline-containing regimens in the adjuvant treatment of

such patients.

Two randomized prospective trials of CEF chemotherapy in

ALN-positive breast cancer are available. In one trial, premenopausal