1. Cynthia Campbell-Baird, RN, OCN Research Nurse Coordinator Department of Medicine/Oncology Penn State Hershey Medical Center Hershey, Pennsylvania Clinical Management of Skeletal Integrity in Breast Cancer: The Role of the Oncology Nurse in Optimizing Patient Outcomes This program is supported by an educational donation from

2. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Breast Cancer Incidence  The incidence of invasive breast cancer in the United States was ~ 192,000 new cases in 2009 [1] –80,000-90,000 patients will relapse and 3/4 of these have bone metastasis  Breast cancer is the most frequently diagnosed cancer in women and the second leading cause of death [2]  Risk factors include: –Age –Sex –Weight gain –Hormonal therapy 1. American Cancer Society. Breast cancer facts & figures 2009-2010. Available at http://www.cancer.org/Research/CancerFactsFigures/index. 2. American Cancer Society. Cancer facts & figures 2010. Available at http://www.cancer.org/Research/CancerFactsFigures/index http://www.cancer.org/Research/CancerFactsFigures/index –Physical inactivity –Personal family history –Alcohol abuse

3. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer 1. National Cancer Institute. Available at: http://seer.cancer.gov. Breast Cancer Survival  Early detection has led to the decrease in numbers of deaths per yr –Includes self-exams, mammography, MRI for those with increased risk, ultrasound/biopsy, and assessment of tumor markers as indicated  Overall 5-yr survival today [1] : ~ 90% –Localized disease: 98% –Regional lymph node involvement: 84% –Distant (metastatic): 23%

4. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Cancer-Induced Bone Disease: Scope of the Problem  > 500,000 patients in United States have cancer-induced bone disease  Two thirds of breast cancer patients have cancer-induced bone loss  Often only site of metastatic disease in cancers that have spread outside the tumor area, especially in breast cancer patients  Prolonged survival is often measured in yrs, not wks or mos  Major clinical consequences for patients, families, and society

5. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Cancer Bone Disease: Prevalence 5-Yr World Prevalence, Thousands [1] Incidence in Advanced Cancers, % [2] Median Survival, Mos [2-5] Breast440665-7519-25 Prostate236965-7512-53 Lung136930-406-7 Bladder1110406-9 Melanoma64314-45< 6 Renal58620-2512 Thyroid5316048 1. Ferlay J, et al. IARC Globocon 2000. Availalbe at http://www-dep.iarc.fr/. 2. Coleman RE. Cancer Treat Rev. 2001;27:165-176. 3. Coleman RE. Cancer. 1997;80:1588-1594. 4. Zekri J, et al. Int J Oncol. 2001;19:379-382.

6. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Bone Loss Is Accelerated With Cancer Therapies 1. Kanis JA. Osteoporosis. Blackwell Healthcare Communications Ltd.; 1997. pp. 22-55. 2. Eastell R, et al. J Bone Mineral Res. 2002;17(suppl 2). Abstract 1170. 3. Maillefert JF, et al. J Urol. 1999;161:1219-1222. 4. Gnant M, et al. SABCS 2002. Abstract 12. 5. Shapiro CL, et al. J Clin Oncol. 2001;19:3306-3311. Yearly Bone Loss, % Normal men [1] 0.5 Postmenopausal women [1] 1.0 Menopausal women [1] 2.0 AI therapy in postmenopausal women [2] 2.6 ADT [3] 4.6 AI therapy plus GnRH agonist in premenopausal women [4] 7.0 Premature menopause secondary to chemotherapy [5] 7.7

7. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Hormonal Therapy  ~ 80% of breast cancer cells are ER positive –Most estrogen is made by the ovaries –The adrenals, muscle, and fat cells also produce androgen (aromatase converts androgen to estrogen)  If ER positive, estrogen causes the breast cancer to grow –Decreasing estrogen may shrink or slow the growth of cancer cells  In addition to AIs, some premenopausal women are given GnRH agonist as well –Examples of AIs: anastrozole, exemestane, letrozole –Examples of GnRH agonists: leuprolide, goserelin

8. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Breast Cancer Therapies and Bone Loss  In the last 15 yrs, AIs have emerged as the cornerstone of the adjuvant treatment of postmenopausal women with hormone receptor–positive breast cancer –AIs are associated with treatment-induced bone loss  Many other therapies used in breast cancer can induce bone loss, most often due to hypogonadism  Estrogens act to restrain bone resorption; therefore, reductions in estrogen levels (eg, oophorectomy) can lead to accelerated bone resorption accompanied by lags in bone formation and further bone loss  Tamoxifen has been shown to demonstrate a loss of BMD in premenopausal patients and modest protection of BMD in postmenopausal patients

9. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Breast Cancer Therapies and Bone Loss: Management Strategies  Effective management and treatment strategies are emerging that include the requirement for a DEXA baseline assessment  Risk-adapted monitoring, intervention strategies, and use of bisphosphonates and other newer classes of bone- directed therapies are also effective at preventing bone loss  Nurses may use the WHO’s online FRAX tool to assess patient’s 10-yr risk of fracture (http://www.shef.ac.uk/FRA)

10. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Bone Complications of Breast Cancer  Bone complications include –Osteoporosis –Bone metastasis –Fractures  Many women are still not being screened for bone loss despite having risk factors  An estimated 9 million women older than 50 yrs of age in United States have osteoporosis [1]  Osteoporosis is often underrecognized and undertreated 1. National Osteoporosis Foundation. Available at: http://www.nof.org.

11. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer  Bone health and the potential for bone loss may be overlooked when a breast cancer diagnosis is made, as the focus often is on the disease  Nurses have the ability to see what the patient is not always able to see  The risk factors for osteoporosis include: –Race –Sex/age –Family history –Small frame/thin –Decreased sex hormones Osteoporosis –Diet (decreased calcium, vitamin D, increased protein, sodium, caffeine) –Inactive lifestyle –Tobacco use –Alcohol abuse –Certain medications –Other diseases National Osteoporosis Foundation. Available at: http://www.nof.org.

12. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Hormonal Deprivation: Effects Loss of gonadal hormones increases bone resorption  Osteoblastic cell activity and life span are decreased, resulting in less new bone  Osteoclastic activity is less suppressed, increasing the rate of resorption Osteopenia and osteoporosis become common

13. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Osteoporosis From Hormonal Deprivation  Normally seen in both aging men and women  Fracture in spine most prevalent  Trabecular (spongy) bone at highest risk  Deprivation accelerated by systemic cancer therapy for all cancers  Especially problematic in antihormonal cancer therapy for breast cancer

14. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Consequences of Bone Loss  Severe bone pain  Fractures  Spinal cord compression  May lead to limited mobility  Hypercalcemia of malignancy  Decrease in quality of life Gralow JR, et al. J Natl Compr Canc Netw. 2009;7(suppl 3):S1-S32.

15. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Bone Remodeling  Continuous throughout life  Osteoblasts: cells that create bone  Osteoclasts: cells that break down bone  Osteoblastic and osteoclastic activity is tightly coupled and balanced  Ensures skeletal integrity  Maintains mineral homeostasis

16. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Types of Cancer-Related Bone Disease Osteoblastic  Prostate and breast  Bone formation mediated by osteoblasts Osteolytic  Breast and myeloma  Bone destruction mediated by osteoclasts

17. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Metastatic Bone Disease in Breast Cancer  Breast cancer patients may have either osteolytic or osteoblastic bone or both –Osteolytic: “punched out” area of severe bone loss –Osteoblastic: deposits of bone, but not healthy bone  Breast cancer may metastasize to the bone due to –Increased blood flow in the marrow –Active hematopoiesis –Increased amounts of growth factors

18. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Pathogenesis of Osteolytic Bone Metastases “Vicious Cycle”  Tumor-derived. osteoclast-activating growth factors –Parathyroid hormone– related protein –Interleukin-6, -8, -11 –Tumor necrosis factor –Macrophage colony- stimulating factor  Bone-derived tumor growth factors (have a direct effect on osteoclast differentiation) –Transforming growth factor  –Insulin-like growth factors –Fibroblast growth factors –Platelet-derived growth factor –Bone morphogenetic proteins Bone Tumor cells in bone (osteoclast differentiation) Active osteoclast (+) Derived from Roodman GD. N Engl J Med. 2004;350:1655-1664.

19. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Common Sites of Bone Metastasis  Usually heavily vascularized areas –Pelvis: 40% –Ribs: 58% –Vertebrae: 54% –Less frequently to appendicular skeleton: 32% Nakamoto Y, et al. Clin Nucl Med. 2003;28:302-307.

20. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer SREs Reflect Morbidity From Bone Metastases  Pathological fractures –Nonvertebral –Vertebral compression  Spinal cord compression/collapse  Radiation therapy  Surgery to bone  Hypercalcemia of malignancy  SREs related to > $19 billion in costs in 2005 and expected to reach $25 billion by 2025 SREs American Cancer Society. Available at http://www.cancer.org.

21. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Bone-Targeted Therapies: Bisphosphonates  Bisphosphonates are the standard of care for reducing the risk of SREs with metastatic bone disease  Bisphosphonates increase bone mineral density by –Decreasing bone resorption and increasing mineralization –Interfering with the activity of osteoclasts –Inhibiting calcium from being released from the bone

22. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Mechanism of Bisphosphonate Inhibition of Osteoclast Activity Bisphosphonates inhibit osteoclast activity, and promote osteoclast apoptosis [1] Bisphosphonates are released locally during bone resorption [1] Bisphosphonates are concentrated under osteoclasts [1] Bisphosphonates may modulate signaling from osteoblasts to osteoclasts New bone X Bone  Increased OPG production [2]  Decreased RANKL expression [3] 1. Reszka AA, et al. Curr Rheumatol Rep. 2003;5:65-74. 2. Viereck V, et al. Biochem Biophys Res Commun. 2002;291:680-686. 3. Pan B, et al. J Bone Miner Res. 2004;19:147-154.

23. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Bisphosphonates Zoledronic acid: FDA approved for the treatment of multiple myeloma or cancer from solid tumors that has spread to the bone (including breast cancer), in combination with standard chemotherapy agents. Also approved for the treatment of hypercalcemia of malignancy. WIDELY USED IN BREAST CANCER. Pamidronate: FDA approved for the treatment of hypercalcemia of malignancy. It is also used to prevent or delay bone damage caused by multiple myeloma or breast cancer that has spread to the bone. Markedly reduces skeletal morbidity.

24. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Other Bisphosphonates Ibandronate: osteoporosis medication that is used in postmenopausal women. Risedronate and alendronate: used to prevent and treat osteoporosis in postmenopausal women and in men and women who are taking glucocorticoids. It is also used to treat osteoporosis in men and Paget’s disease of bone.

25. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Bisphosphonates: Adverse Effects IV bisphosphonates (zoledronic acid, pamidronate) [1,2]  Zoledronic acid: most potent  Treatment of osteoporosis  Prevention/decrease of onset fractures  Provides pain relief in bone metastasis, improves quality of life, and antitumor effects Adverse effects:  Bone pain: responsive to NSAIDs  Nausea (minor)  Flulike symptoms  Anemia  Hypocalcemia  ONJ (rare) 1. Doggrell SA. Expert Rev Anticancer Ther. 2009;9:1211-1218. 2. Winter MC, et al. Curr Opin Oncol. 2009;21:499-506.

26. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Bisphosphonates: Adverse Effects Oral bisphosphonates (alendronate, risedronate, ibandronate) [1] Adverse effects  GI disturbance/toxicity –Tablets may not be chewed or dissolved in mouth –Take with 8 ounces of water in upright position –No food or drink for 30 mins after taking –Avoid in patients with esophageal emptying disorders  Bone pain: diffuse and can be disabling  ONJ (rare)  Poor compliance: 25% compliance rate first yr 1. Papapetrou PD. Hormones (Athens). 2009;8:96-110.

27. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Nursing Consideration: ONJ  ONJ is a class effect and has been observed with both bisphosphonates and with the RANKL-targeting agent denosumab.  Managing ONJ first involves making an accurate diagnosis  ONJ may be mostly preventable with good dental care –A randomized trial is under way to further evaluate the role of dental care in preventing ONJ –Lack of insurance for dental treatment can be a barrier to patients receiving a baseline dental checkup  Nurses should assess each patient and strongly encourage patients to ensure that oral hygiene is adequate before therapy is started

28. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer RANK Ligand: A Major Driver of Osteoclast Differentiation  RANKL is expressed on the surface of osteoblasts  RANKL binds to the RANK receptor on osteoclast precursor cells, promoting osteoclast formation and prolonging osteoclast life span  The effects of RANKL are blocked by OPG  OPG acts as a decoy receptor for RANKL  When OPG is secreted in sufficient quantities, RANKL-RANK binding is diminished and osteoclast formation is suppressed  Systemic and local factors can modulate bone resorption through affecting the RANK/RANKL/OPG system Boyce B, et al. Arthritis Res Ther. 2007;9(suppl 1):S1.

29. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Denosumab May Interrupt the “Vicious Cycle” of Cancer-Induced Bone Destruction PDGF, BMPs TGF-β, IGFs FGFs Osteoblasts RANKL RANK Denosumab Tumor cell Formation inhibited Apoptotic osteoclast PTHrP, BMP, TGF-β, IGF, FGF, VEGF, ET1, WNT Adapted from Roodman D. N Engl J Med. 2004;350:1655.

30. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Denosumab: Inhibiting RANKL in Bone Disease  Human monoclonal antibody with high affinity for RANKL; does not bind to other growth factors  Inhibits formation and activation of osteoclasts  Administered via SC injection [1]  Recently approved for the treatment and prevention of postmenopausal bone loss  Demonstrated potential for improving outcomes compared with zoledronic acid [2]  Other bone-targeted agents are in development 1. Food and Drug Administration. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. 2. Stopeck A, et al. SABCS 2009. Abstract 22. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails

31. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Phase III Study: Denosumab During AI Therapy for Early Breast Cancer  Multicenter, randomized, double-blind, placebo-controlled study conducted in the United States and Canada Baseline 12 Mos 24 Mos Women receiving adjuvant AI therapy for ER-positive breast cancer (N = 252) Ellis G, et al. J Clin Oncol. 2008:26:4875-4882. Denosumab 60 mg SC q6m x 4 (n = 127) Placebo SC q6m x 4 (n = 125)

32. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Ellis G, et al. J Clin Oncol. 2008:26:4875-4882. Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved. *P <.0001 vs placebo. Change (± 95% CI) From Baseline in L-Spine BMD (%) 8 6 4 2 0 -2 7 5 3 1 -3 * * * * * 1361224 5.5% difference at Mo12 Denosumab (n = 123)Placebo (n = 122) 7.6% difference at Mo 24 Mos Effect of Denosumab on Lumbar Spine BMD

33. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Denosumab vs Zoledronic Acid in Advanced Breast Cancer: Phase III Study Zoledronic acid 4 mg IV* + Placebo SC q4w (n = 1020) Denosumab 120 mg SC + Placebo IV* q4w (n = 1026) Supplemental Calcium and Vitamin D Key inclusion criteria  Adults with advanced breast cancer and confirmed bone metastases Key exclusion criteria  Current or previous IV bisphosphonate administration *IV product dose adjusted for baseline creatinine clearance and subsequent dose intervals determined by serum creatinine (per zoledronic acid label). Stopeck A, et al. SABCS 2009. Abstract 22.

34. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Phase III Trial: Time to First On-Study SRE Stopeck A, et al. SABCS 2009. Abstract 22.  Median time to first on-study SRE superior with denosumab –Denosumab: not reached –Zoledronic acid: 26.5 months –HR: 0.82 (95% CI: 0.71-0.95) – P <.0001 for noninferiority – P =.01 for superiority)

35. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Phase III Trial: Adverse Events Event, n (%) Zoledronic Acid (n = 1013) Denosumab (n = 1020) Infectious AEs494 (48.8)473 (46.4) Acute phase reactions (first 3 days)277 (27.3)106 (10.4) Potential renal toxicity AEs*86 (8.5)50 (4.9)  Renal failure25 (2.5)2 (0.2) Cumulative rate of ONJ † 14 (1.4)20 (2.0)  Yr 15 (0.5)8 (0.8)  Yr 212 (1.2)19 (1.9) *Includes blood creatinine increased, hypercreatinemia, oliguria, renal impairment, proteinuria, renal failure, urine output decreased, creatinine renal clearance decreased, renal failure acute, renal function test abnormal, anuria, blood urea increased, renal failure chronic. † P = 0.39 No neutralizing antidenosumab antibodies were detected. Stopeck A, et al. SABCS 2009. Abstract 22.

36. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Bone-Targeted Agents: Incremental Benefits in Breast Cancer Lipton A, et al. Cancer. 2000;88:3033-3037. Rosen LS, et al. Cancer. 2003;100:36-43. Stopeck A, et al. ECCO/ESMO 2009. Abstract 20LBA. 64% risk of skeletal complication with no bisphosphonate at 2 yrs ~ 33% risk reduction with pamidronate 64%43%34% Further 20% risk reduction with zoledronic acid 27% Additional 18% risk reduction with Denosumab

37. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Bone-Targeted Agents: Summary Bisphosphonates  Important component of breast cancer management  Reduces number and severity of skeletal complications  Prevents cancer treatment–induced bone loss  May prevent/interrupt the metastatic process and reduce recurrences  Incidence of acute-phase reactions may be underreported and may accompany not only the first but also the second and third infusions –Some patients may discontinue therapy. –Caregivers should remain aware of the possibility that these reactions may occur  Incidence of renal failure and renal toxicity higher with zoledronic acid vs denosumab

38. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Bone-Targeted Agents: Summary Denosumab  Currently being investigated in cancer treatment–induced bone loss  Rapid and sustained reduction in bone resorption  Associated with a rapid increase in BMD during AI treatment  Apparent improvement in reducing SREs compared with zoledronic acid

39. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Bone Health Management: The Nurse’s Role Assessing Bone Health Risks:  WHO FRAX tool is widely used by health professionals for evaluating the risk of fracture in patients (http://www.shef.ac.uk/ FRAX)  Cancer-specific considerations –10-yr increase in risk for fracture with breast cancer –Treatment can directly affect the bone –Metastasis in later stages weakens bones –Potential sedentary lifestyle –Diet changes brought on by treatment modalities –A thorough nursing assessment of bone issues is essential  Age –Osteoporosis can accompany normal aging –Lifestyle changes from aging affect bone health  Fall risks (ie, impaired vision, poor health/frailty, history of recent falls)  Tobacco use  Alcohol abuse  Women at or near menopause

40. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Interventions for Maintaining Bone Health in Patients  Therapeutic treatment options  Pharmacologic treatment options  Exercise –Weight-bearing exercise facilitates normal remodeling –Keeping it simple enhances compliance; walk!  Diet: provide nutritional counseling when possible –Moderate protein intake –Limited sodium (salt) intake –Calcium and vitamin D are essential for building bone (food best source) –Calcium intake should be spread out throughout the day –Calcium may be affected by many things including proton pump inhibitors and caffeine –Calcium supplements also have different rates of absorption, with calcium carbonate being the best absorbed –The National Osteoporosis Foundation recommends 1200 mg calcium for women older than 50 yrs of age and vitamin D 800-1000 IU/day

41. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Screening for Cancer-Induced Bone Loss  ASCO guidelines for BMD screening in breast cancer patients [1] –All women 65 yrs of age or older –All women 60-64 yrs of age with –Family history of breast cancer –Body weight < 70 kg –Previous nontraumatic fracture –Other risk factors –Postmenopausal women of any age receiving AIs –Premenopausal women with therapy-associated premature menopause  Repeat BMD yearly after initial exam in breast cancer (not always covered by insurance) 1. Hillner BE, et al. J Clin Oncol. 2003;21:4042-4057.

42. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer WHO: Criteria for Assessing Bone Density Kanis JA, et al. J Bone Miner Res. 1994;9:1137-1141. National Osteoporosis Foundation, 2003. DiagnosisT-Score* Normal> -1 Osteopenia-1.0 to -2.5 Osteoporosis  -2.5 Severe osteoporosis  -2.5 and  1.0 fracture *Indicates how much a person’s bone mass deviates from an average healthy adult.

43. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Radiologic Assessment  Central and peripheral DEXA is the gold standard –Measures BMD –Also important for basic health screening  NCCN guidelines for initiating treatment [1] –T-score > -1.0: watchful waiting with DEXA every 2 yrs –T-score between -1.0 and -1.5: vitamin D monitored and DEXA every 2 yrs –T-score between -1.5 to -2.0: consider treatment –T-score < -2.0: treatment strongly recommended  MRI/CT/skeletal bone survey –Characterizes bone lesions –Detects lytic and sclerotic lesions  Nuclear bone scan (preferred) –Used to assess blastic bone metastases with greater visibility 1. Gralow JR, et al. J Natl Compr Cancer Netw. 2009;7(suppl 3):1-32.

44. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Nursing Considerations: Bone-Targeted Agents  Bisphosphonates, including pamidronate and zoledronic acid, have been shown to markedly reduce skeletal morbidity  Denosumab, a monoclonal antibody that targets RANKL, has been found to improve outcomes for patients compared with zoledronic acid in patients with breast cancer; many other bone-targeted agents are in development  Nurses play a central role in administering these agents and recognizing and managing the adverse events associated with bone-directed therapies, including renal toxicity and ONJ

45. clinicaloptions.com/oncology Clinical Management of Skeletal Integrity in Breast Cancer Overall Nursing Considerations  Assess the patient’s needs, letting them know available options and tests; always ask direct questions that require an answer, not simply “yes” or “no”  Determine which resources they have/need and what is important to them  Determine what they understand about their disease and overall bone health  Provide supportive/restorative care and prevent immobilization  Determine how they define quality of life

46. More CCO Hematology/Oncology Programs Available Online! Medical Meeting Coverage: key data plus Expert Analysis panel discussions exploring clinical implications Treatment Updates: comprehensive programs covering the most important new concepts Interactive Cases: test your ability to manage patients clinicaloptions.com/oncology