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-47

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

human monoclonal antibody directed against RANK ligand, a mediator

of osteoclast function

413

as compared with zoledronic acid.

412

No study

of bisphosphonate or denosumab has demonstrated an impact on OS

in patients with metastatic disease.

The bisphosphonates and denosumab are associated with the

occurrence of osteonecrosis of the jaw (ONJ). Poor baseline dental

health or dental procedures during treatment are known risk factors for

ONJ. Thus, a dental examination with preventive dentistry intervention

is recommended prior to treatment with intravenous bisphosphonate or

denosumab, and dental procedures during treatment should be avoided

if at all possible. Additional risk factors for the development of ONJ

include administration of chemotherapy or corticosteroids and poor oral

hygiene with periodontal disease and dental abscess.

414

Confirmation of metastatic disease by imaging, including x-ray,

diagnostic CT, or MRI; and initial evaluation of serum calcium,

creatinine, phosphorous, and magnesium levels should be undertaken

prior to the initiation of intravenous bisphosphonate treatment or

subcutaneous denosumab treatment in patients with metastatic

disease. Frequent measurement of calcium, phosphorous, and

magnesium may be prudent since hypophosphatemia and

hypocalcemia have been reported.

Bisphosphonates

An intravenous bisphosphonate (eg, pamidronate, zoledronic acid) in

combination with oral calcium citrate and vitamin D supplementation

should be used in women with bone metastasis, especially if lytic and/or

in weight-bearing bone, if expected survival is 3 months or longer, and if

creatinine levels are below 3.0 mg/dL (category 1).

411,415-420

Bisphosphonates are given in addition to chemotherapy or endocrine

therapy. Zoledronic acid may be superior to pamidronate in lytic breast

metastasis.

421,422

There are extensive data from randomized trials in support of the use of

bisphosphonates for patients with metastatic disease to bone. The

randomized clinical trial data include the use of zoledronic acid and

pamidronate in the United States and ibandronate and clodronate in

European countries.

418,420,422-427

In metastatic bone disease,

bisphosphonate treatment is associated with fewer skeletal-related

events, fewer pathologic fractures, and less need for radiation therapy

and surgery to treat bone pain.

The use of bisphosphonates in metastatic disease is a palliative care

measure. No impact on OS has been observed in patients treated with

bisphosphonates. The data indicate that zoledronic acid and

pamidronate may be given on a 3- to 5-week schedule in conjunction

with antineoplastic therapy (ie, endocrine therapy, chemotherapy,

biologic therapy). The use of bisphosphonates should be accompanied

by calcium and vitamin D supplementation with daily doses of calcium

of 1200 to 1500 mg and vitamin D

400 to 800 IU. Recommended

agents for use in the United States are pamidronate 90 mg

intravenously over 2 hours or zoledronic acid 4 mg intravenously over

15 minutes. The original studies continued treatment for up to 24

months; however, there are limited long-term safety data indicating

treatment can continue beyond that time.

425,427,428

The risk of renal

toxicity necessitates monitoring of serum creatinine prior to

administration of each dose and dose reduction or discontinuation if

renal function is reduced. Current clinical trial results support the use of

bisphosphonates for up to 2 years. Longer durations of bisphosphonate

therapy may provide additional benefit, but this has not yet been tested

in clinical trials.