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-29

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

reduction in risk of progression, possibly due to a “carryover effect.” The

reduction in risk of recurrence was 0.90 (95% CI, 0.79–1.02) during 5 to

9 years of tamoxifen treatment and 0.75 (0.62–0.90) after 10 years.

Furthermore, reduced mortality was apparent after completion of 10

years of treatment with tamoxifen. With regards to toxicity, the most

important adverse effects noted in all women in ATLAS were an

increased risk of endometrial cancer after treatment with 10 years of

tamoxifen and pulmonary embolism. The recurrence rate ratios for

incidence of adverse events (hospitalization or death) were: pulmonary

embolus 1.87 (95% CI, 1.13–3.07,

= .01 [including 0.2% mortality in

both treatment groups]), stroke 1.06 (0.83–1.36), ischemic heart

disease 0.76 (0.60–0.95,

= .02), and endometrial cancer 1.74 (1.30–

2.34,

= .0002). The cumulative risk for endometrial cancers during 5

to 14 years was 3.1%, with a mortality of 0.4% associated with

endometrial cancer, higher than what was noted in the control group of

patients receiving only 5 years of therapy (cumulative risk: 1.6%;

mortality: 0.2%).

265

Results are expected in the near future of other ongoing trials of

extended tamoxifen, such as the aTTom trial of 5 years versus 10 years

tamoxifen with 7000 women, are expected in the near future.

Preliminary results of this trial have shown that continuation of

tamoxifen beyond 5 years resulted in a non-significant reduction in

recurrences.

266

The role of adjuvant ovarian ablation or suppression in premenopausal

women with hormone receptor-positive breast cancer is incompletely

defined.

267-269

Ovarian ablation may be accomplished by surgical

oophorectomy or by ovarian irradiation. Ovarian suppression utilizes

luteinizing hormone-releasing hormone (LH-RH) agonists that result in

suppression of luteinizing hormone (LH) and release of follicle

stimulating hormone (FSH) from the pituitary and reduction in ovarian

estrogen production. Available LH-RH agonists in the United States

include goserelin and leuprolide and, when used for ovarian

suppression, both agents should be given as monthly injections.

The

EBCTCG

performed a meta-analysis of randomized studies of

ovarian ablation or suppression alone versus no adjuvant treatment in

women >50 years, with many of the subjects in the trials unselected

based upon hormone receptor status. In this study there were

reductions in the annual odds of recurrence and of death favoring

ovarian ablation/suppression over no adjuvant treatment (age <40

years: 25% reduction in recurrence rate and 29% reduction in death

rate; age 40–49 years: 29% reduction in recurrence rate and 29%

reduction in death rate).

268

Analysis of ovarian suppression versus no

adjuvant therapy did not demonstrate significant reduction in recurrence

(HR reduction, 28.4, 95% CI, 50.5– 3.5;

= .08) or death (HR

reduction, 22, 95% CI, 4.1– 6.4;

= .11).

270

Studies in premenopausal women of ovarian ablation or suppression

alone versus CMF chemotherapy alone generally demonstrate similar

antitumor efficacy in patients with hormone receptor-positive tumors and

superior outcomes with CMF in patients with hormone receptor-negative

tumors.

270-278

There is also the suggestion that the benefits to ovarian

suppression/ablation may be greater in the younger premenopausal

group.

Studies in premenopausal women of ovarian ablation/suppression plus

tamoxifen versus chemotherapy alone generally demonstrate no

difference in rates of recurrence or survival.

268,279,280

A large intergroup study in premenopausal women with hormone

receptor-positive, node-positive breast cancer studied adjuvant CAF

(cyclophosphamide/doxorubicin/5-fluorouracil) chemotherapy versus