NCCN VERSION 2 2015

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MS-32

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

associated with significant increases in both DFS (HR, 0.66; 95% CI,

0.44–1.00;

= .049) and OS (HR, 0.0.53; 95% CI, 0.28–0.99;

.045).

282

A meta-analysis of ABCSG 8, ARNO 95, and ITA studies

showed significant improvement in OS (HR, 0.71, 95% CI, 0.5200.98;

= .04) with a switch to anastrozole.

300

The TEAM trial compared sequential treatment of exemestane alone

versus sequential therapy of tamoxifen for 2.5 to 3.0 years followed by

exemestane to complete 5 years of hormone therapy.

301

At the end of 5

years, 85% of patients in the sequential group versus 86% in the

exemestane group were disease free (HR, 0.97; 95% CI, 0.88–1.08;

= .60). This is consistent with the data from the BIG 1-98 trial,

295

which tamoxifen followed by letrozole or the reverse sequence of

letrozole followed by tamoxifen was not associated with significant

differences in efficacy versus letrozole monotherapy after a median

follow-up of 71 months.

Results of the MA-17 trial in 5187 women who had completed 4.5 to 6

years of adjuvant tamoxifen demonstrated that extended therapy with

letrozole provides benefit in postmenopausal women with hormone

receptor-positive, early breast cancer.

283,302

At a median follow-up of 2.5

years, the results showed fewer recurrences or new contralateral breast

cancers with extended letrozole (HR, 0.58; 95% CI, 0.45– 0.76;

P <

.001). No difference in OS was demonstrated (HR, 0.82; 95% CI, 0.57–

1.19;

= .3), although there was a survival advantage in the subset of

patients with ALN-positive disease (HR 0.61; 95% CI, 0.38–0.98;

.04). In a separate cohort analysis of the MA-17 trial, the efficacy of

letrozole versus placebo was evaluated after un-blinding of the study in

the 1579 women who had been randomly assigned to placebo after 4.5

to 6 years of tamoxifen.

303,304

The median time since completion of

tamoxifen was 2.8 years. Both DFS and distant DFS were significantly

improved in the group receiving letrozole, thereby providing some

evidence for the efficacy of letrozole in patients who had received 4.5 to

6 years of tamoxifen therapy followed by no endocrine therapy for an

extended period. A formal quality-of-life analysis demonstrated

reasonable preservation of quality of life during extended endocrine

therapy, although women may experience ongoing menopausal

symptoms and loss of bone mineral density.

305,306

No data are available

regarding use of aromatase inhibitors for more than 5 years or

long-term toxic effects from extended treatment. In addition, the ATLAS

trial data does not provide clear direction for treatment of

postmenopausal women.

265

There are no data available to suggest that

an aromatase inhibitor for 5 years is better for long-term benefit than 10

years of tamoxifen.

In the extension study of ABCSG trial 6, hormone receptor-positive

postmenopausal patients received 5 years of adjuvant tamoxifen and

were randomized to 3 years of anastrozole or no further therapy.

307

At a

median follow-up of 62.3 months, women who received anastrozole (n =

387) were reported to have a statistically significantly reduced risk of

recurrence compared with women who received no further treatment (n

= 469; HR, 0.62; 95% CI, 0.40– 0.96;

= .031).

307

The differences in design and patient populations among the studies of

the aromatase inhibitors do not allow for the direct comparison of the

results of these studies. A meta-analysis of adjuvant trials of aromatase

inhibitors versus tamoxifen alone versus after 2 or 3 years of tamoxifen

documented lower recurrence rates with the aromatase

inhibitor-containing regimen, with no clear impact on OS.

308

It is not

known whether initial, sequential, or extended use of adjuvant

aromatase inhibitors is the optimal strategy.

The optimal duration of aromatase inhibitor treatment is also not known,

nor is the optimal use vis-à-vis chemotherapy established. Further, the