BONE HEALTH and. what you need to know

Transcription

1 BONE HEALTH and BREAST cancer: what you need to know

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3 Bone Health and Breast Cancer: What You Need To Know TABLE OF CONTENTS ABOUT BONE METASTASES...4 HOW DOES CANCER SPREAD & DESTROY THE BONE?...4 ABOUT SKELETAL-RELATED EVENTS (SREs)...5 BONE METASTASES & SKELETAL-RELATED EVENTS IN BREAST CANCER...6 HOW ARE BONE METASTASES DIAGNOSED?...7 ARE THERE TREATMENTS FOR BONE METASTASES & SKELETAL-RELATED EVENTS?...8 ROLE OF RANK LIGAND IN BONE BIOLOGY...9 NEXT STEPS: SERIOUS CONSEQUENCES REQUIRE PROACTIVE COMMUNICATION...10 KEY QUESTIONS TO ASK YOUR PHYSICIAN...11 GLOSSARY...12 REFERENCES

4 ABOUT BONE METASTASES The spread of cancer to a secondary site is known as metastatic disease and one of the most common places for certain cancers to spread is to the bone. Bone metastases occur when cancer cells separate from the site of the primary tumour and migrate to bone tissue where they settle and grow. These growing cancer cells then weaken and destroy the bone around the tumour and can result in a number of serious complications, collectively called skeletal-related events (SREs), which are associated with disability and death. 1,2 Sixty-five to 75 per cent of people with advanced breast cancer can eventually develop bone metastases throughout the course of their disease. 1 Bone pain is one of the first signs that cancer has progressed this far. 3 Bone pain dominates the daily lives of people with metastatic disease and can severely affect a patient s quality of life. 4 In fact, up to two-thirds of people with bone metastases experience severe and debilitating bone pain. 5 Treating bone pain and preventing SREs is an important part of managing metastatic bone disease and should be included as part of the dialogue between physicians and patients. HOW DOES CANCER SPREAD & DESTROY THE BONE? 6 When cancer metastasizes to the bone, it triggers a cycle of bone destruction and tumour growth. Here s how it works: cancer cells travel from the original tumour site to the bone where they stimulate bone cells called osteoclasts to increase bone destruction. This increase in bone breakdown makes room in the bone for the tumour to grow. In addition, as the bone is destroyed, proteins are released from the bone that can cause cancer cells to grow, continuing the cycle of bone destruction. 4

5 ABOUT SKELETAL-RELATED EVENTS (SREs) Once cancer has spread to the bone, a number of serious complications can occur. Collectively, these are called skeletal-related events (SREs) and can include broken bones, and spinal cord compression, as well as the need for radiation and/or surgery to the bone. In people with advanced cancer, bone metastases can lead to debilitating SREs, which are associated with increased disability and death, and can place a significant economic burden on the healthcare system. 7 PATHOLOGICAL FRACTURE A fracture to bone for a patient with advanced cancer is significant and can require surgery. It can cause serious impairment and disability in addition to pain. 1 SPINAL CORD COMPRESSION If the bone metastasis is in or around the vertebral column, expansion from the bone can put pressure on the spinal cord. This can lead to serious complications such as numbness, incontinence and paralysis. 8 SURGERY TO BONE Surgery can help prevent and heal fractures. Most fractures do not heal properly without surgery (or radiotherapy) and require rehabilitation to restore function. 9 RADIATION TO BONE Radiation to the bone is performed to treat the bone metastasis and alleviate pain. However, due to the effects of radiation on the bone, it is generally only performed on smaller (localized) areas. 10 Two current trends in radiation therapy for bone pain are hypofractionation, in which oncologists administer fewer larger radiation doses rather than many smaller doses, 11 and sterotactic body radiation therapy in which the dose is focused on a specific portion of bone or other tissue, often over several days. 12,13 5

6 BONE METASTASES & SKELETAL-RELATED EVENTS IN BREAST CANCER Sixty-five to 75 per cent of people with advanced breast cancer can eventually develop bone metastases throughout the course of their disease. 1 Nearly 64 per cent of people with breast cancer who have bone metastases experience an SRE if left untreated, suffering uncontrollable pain and difficulty with daily functions. 14 SREs are also associated with additional negative consequences, as people with breast cancer without a fracture have been shown to survive longer than those who experience a fracture. 15 6

7 HOW ARE BONE METASTASES DIAGNOSED? There are several signs and symptoms of bone metastases, including bone pain, fractures or hypercalcemia (a result of excess calcium released into the blood stream). Symptoms of hypercalcemia can include nausea, constipation, kidney stones, memory loss and depression. 16 A doctor may order several tests to see if the cancer has spread to the bones, including: hh hh hh hh Imaging tests: X-rays and radionuclide bone scans, computed tomography [CT] scans, magnetic resonance imaging (MRI) scans and positron emission tomography [PET] scans; Blood tests: serum tumour markers and other blood tests; for example, tests to measure levels of calcium and alkaline phosphatase (Any condition that affects bone growth or causes increased activity of bone cells can affect alkaline phosphatase levels in the blood); 17 Urine tests; Tissue and cell sampling tests: needle biopsies, fine needle biopsies or aspirations, core needle biopsies and surgical bone biopsies. 18 X-rays of Normal Bone and Bone Metastasis These x-rays show the bone destruction that occurs due to bone metastases: normal bone Bone metastasis 7

8 ARE THERE TREATMENTS FOR BONE METASTASES & SKELETAL-RELATED EVENTS? Current understanding of how bones grow and weaken has resulted in the use of drugs called bisphosphonates to treat bone metastases. 19 While these treatment options are underutilized, they can help delay or prevent SREs associated with bone metastases, and improved skeletal health may provide important benefits to people with breast cancer. 5 Since their introduction, bisphosphonates have been used for managing metastatic bone disease in people with advanced breast cancer. They have been shown to reduce cancer-related bone complications in specific malignancies by delaying the time to a first SRE and reducing the overall skeletal morbidity rate. 9 Specifically, pamidronate (administered once a month via a two-hour infusion) or clodronate (taken daily in tablet form) are widely used to treat skeletal complications resulting from metastatic disease in people with breast cancer. 20 As with any treatment, however, there are several important factors that may limit the use of bisphosphonates in some people. Regular monitoring of renal (kidney) function is recommended when bisphosphonates are used for people with bone metastases due to the potential consequence of kidney deterioration. 21,22 While bisphosphonate therapy may prove beneficial to patients, based on individual benefit and risk assessments, it may not be appropriate for all patients. Therefore, some patients may go untreated, remaining at risk of SREs. Additionally, there are currently no approved treatments for the prevention or delay of bone metastases, which means that people with advanced cancer can be treated for bone metastases once they have it, but there is no approved treatment to prevent or delay the metastases from happening in the first place. This presents a care gap for people with advanced breast cancer. There are no approved therapies for the prevention of bone metastases. 8

9 ROLE OF RANK LIGAND IN BONE BIOLOGY Bone is living, growing tissue made mostly of collagen. In healthy adults, bone is constantly renewed through a two-part process where special cells called osteoclasts break down and remove old bone tissue (known as bone resorption), while cells called osteoblasts build and lay down new bone tissue to replace the old. 23 During childhood and teen years, the human body produces and lays down new bone tissue faster than the old bone is removed. 23 This is why bones grow to be larger, stronger and denser. As the body ages, the process of bone formation slows down, while the process of bone resorption continues, resulting in a loss of bone density. 23 In the mid-1990s, the discovery of a protein and a signaling pathway called RANK Ligand revolutionized the scientific world s understanding of bone biology, ushering in a new direction for the exploration of treatments for bone diseases. 24 The RANK Ligand pathway consists of several proteins and is a key mediator in the breakdown of bones. These proteins interact to regulate the production of osteoclasts, the cells that break down bone. These proteins include RANK, RANK Ligand, and osteoprotegerin (OPG) the discovery of which helped scientists better understand bone biology and investigate the potential of treating various bone diseases. 24 The following diagram outlines the cycle of bone destruction and growth and how proteins (RANK, RANK Ligand, and osteoprotegerin) contribute to that process. A HYPOTHESIS OF BONE DESTRUCTION IN METASTATIC CANCER AND RANK LIGAND S ROLE Adapted from Roodman D. Mechanisms of bone metastasis. N Engl J Med. 2004: 350:

10 NEXT STEPS: SERIOUS CONSEQUENCES REQUIRE PROACTIVE COMMUNICATION The effective treatment of cancer and its related complications requires a considerable effort by you (the patient) and your physician. Forming a strong partnership, which should also include family, friends, nurses or nurse practitioners, social workers and patient support groups, is not only helpful but crucial to effective disease management and treatment. INFORMATION IS AVAILABLE Knowledge is power. This is especially true for people with breast cancer who can make decisions about their treatment by becoming educated. Information is available to help people with breast cancer understand their diagnosis and treatment options. THE SUPPORT OF FAMILY & FRIENDS A NETWORK OF SUPPORT Having the support and help of friends, as well as loved ones is also very important. Bringing someone along to your medical appointments, for example, not only provides emotional support, but also gives you a critical back-up; someone who can listen carefully to directions, think of questions to ask, and remember details you may have forgotten. KEEP RECORDS To improve and maintain effective communications, you should prepare a list of specific questions beforehand and write down responses from your healthcare providers in order to prevent important concerns from being forgotten during medical appointments. 25 Taking notes will also help you review the information later when there is more time to concentrate or do research. It may even make sense for you to tape-record your visits, with the doctor s consent. 25 People who record their visits can listen to specific information again or share it with family members or friends. Another way for you to record information about your specific diagnosis and keep track of details is to keep a journal or notebook. It is a good way to track not just appointments, blood tests, medications and side effects, but everything that is happening, including your feelings. SPEAK UP In any conversation with a doctor, patients should feel free to be assertive. If you don t know what a word means or don t understand the doctor s directions, you have the right to ask. You can also request a phone appointment or follow-up visit if more time is needed for discussion

11 KEY QUESTIONS TO ASK YOUR PHYSICIAN Here are some questions people with breast cancer can use as a guide for a discussion with their doctors or nurses: 25 What are my treatment options? What is the recommended treatment? Why? How often will I receive treatment? What are the possible side effects of this treatment? What are the possible benefits and risks of this treatment? do you have any additional information I can read about this treatment or procedure? Is there anything else I should know? If my doctor is not available, is there a nurse or nurse practitioner I can contact for more information? 11

12 GLOSSARY BONE a living tissue that provides skeletal support as well as a number of metabolic functions. BONE METASTASES advanced cancer spreading to the bone from elsewhere in the body. CANCER a malignant growth or tumour caused by abnormal and uncontrolled cell division. METASTATIC CANCER Cancer that has spread from the site of origin to other parts of the body. MORBIDITY a diseased state or symptom of disease. OSTEOBLAST a type of bone cell that is responsible for building and laying down new bone tissue ( bone builder ). OSTEOCLAST a type of bone cell that breaks down bone ( bone eater ). RANK LIGand the RANK Ligand pathway consists of several proteins that interact to regulate the production of osteoclasts, the cells that break down bone. The proteins include RANK, RANK Ligand, and osteoprotegerin (OPG). SKELETAL RELATED EVENT a complication that results from bone destruction caused by bone metastases, including fractures, and spinal cord compression, as well as the need for radiation and/or surgery to bone. 12

13 REFERENCES 1 Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80(suppl): Costa L, Badia X, Chow E, Lipton A, Wardley A. Impact of skeletal complications on patients quality of life, mobility, and functional independence. Support Care Cancer. 2008;16: ripamonti C, Fulfaro F. Malignant bone pain: pathophysiology and treatments. Curr Rev Pain. 2000;4: diel IJ. Effectiveness of bisphosphonates on bone pain and quality of life breast cancer patients with metastatic bone disease: A review. Support Care Cancer. 2007: 15: Gralow J, Tripathy, D. Managing metastatic bone pain: the role of bisphosphonates. J Pain Symptom Manage. 2007;33: roodman, G.D. Mechanisms of Bone Metastasis N Engl J Med 2004; 350: Schulman K and Kohles J.Economic burden of metastatic bone disease in the U.S. Cancer.2007: 109(11): dictionary of Cancer Terms spinal cord compression. National Cancer Institute website. Accessed August 31, saad F. Impact of bone metastases on patient s quality of life and importance of treatment. Eur Urol. 2006;5(suppl 5): Janjan NA. Radiation for bone metastases. Cancer. 2000;80: dictionary of Cancer Terms hypofractionation. National Cancer Institute website. Accessed August 31, dictionary of Cancer Terms stereotactic body radiation. National Cancer Institute website. Accessed August 31, Down to the Bone. Cure Today website. Accessed August 31, Lipton A, et al.pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases. Cancer. 2000: 88(5): Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R. Pathologic fractures correlated with reduced survival in patients with malignant bone disease. Cancer. 2007;110: Hypercalcemia. Medical Author: Ruchi Mathur, M.D. Medical Editor: Melissa Conrad Stöppler, MD. Accessed March 9, lab Tests Online ALP Test html Accessed March 9, Last accessed on November 16, Mortimer JE, Schulman K, Kohles JD.Patterns of bisphosponate use in the United States in the treatment of metastatic bone disease. Clin Breast Cancer. 2007: 7(9): Warr D, et al. Use of Bisphosphonates in women with breast cancer: Practice guidelines report #1-11 (version ). Cancer Care Ontario. Available online at on.ca/pdf/pebc1-11f.pdf. Last accessed on June 17, Zometa (zoledronic acid) prescribing information, Novartis. 22 Aredia (pamidronate disodium) prescribing information, Novartis. 23 national Institute of Arthritis and Musculoskeletal and Skin Disease. Bone Health Review. Available online at pdf. Last accessed on June 17, Global RANK Ligand Backgrounder, Amgen, doctor Can We Talk? Cancer Care website. fs_doctor_talk_en.pdf. Accessed November 23,

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