NCCN VERSION 2 2015

NCCN Guidelines Version 2.2015 Breast Cancer

NCCN Guidelines Index Breast Cancer Table of Contents Discussion

therapy. Zoledronic acid may be superior to pamidronate in lytic breast metastasis. 421,422

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

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 3 400 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.

Version 2.2015, 03/11/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. MS-47