Metastatic Breast Cancer
Metastatic breast cancer is incurable, and the goals of treatment are to control symptoms and disease progression, and improve quality of life. The majority of frail elders with metastatic breast cancer will have hormone receptor–positive tumors, and the mainstay of treatment is endocrine therapy. For patients who have not had prior endocrine therapy, the initial use of an aromatase inhibitor is probably the best choice. Upon disease progression, other endocrine agents should be used, including tamoxifen, other aromatase inhibitors, or fulvestrant (Faslodex).
Megestrol acetate or high-dose estrogens are also appropriate in selected patients with slow progression of metastases who have exhausted other hormonal agents. For the frail elder with hormone receptor–positive early breast cancer who develops metastatic disease while being treated with primary endocrine therapy, a similar strategy should be used. Such a treatment plan is likely to control metastases for the lifetime of the patient.
For patients refractory to endocrine therapy or those with hormone receptor–negative breast cancer, single-agent chemotherapy can be tried. Many single agents are well tolerated and can be started in smaller does to minimize toxicity. These include the oral agent capecitabine (Xeloda), weekly low-dose anthracyclines or pegylated liposomal doxorubicin (Doxil), weekly taxanes, vinorelbine, and gemcitabine (Gemzar). For those with HER2-positive tumors, trastuzumab (Herceptin) alone can be considered and is usually well tolerated. Frail elders treated with chemotherapy need to be closely monitored for toxicity.
For patients with bone metastases, radiation administered to affected areas can be most effective. IV bisphosphonates, which can reduce pain and other skeletal events, should be considered for patients with painful lesions. Radiation should also be considered for treatment of central nervous system (CNS) metastases or other localized metastatic lesions. A major issue in many frail elders with CNS metastases is whether to treat at all, especially those with cognitive disorders. The decision to treat must include a careful discussion of the goals of treatment with the patient, her family, and her other caregivers.
At some point, treatment of metastatic cancer becomes futile and such patients should be referred for palliative and hospice care. Such care is also appropriate for frail elders with metastatic disease who decline therapy. This is likely to occur much sooner in frail elders with metastases than in their healthier counterparts.
Breast cancer has been undertreated in elderly individuals, and elders continue to be underrepresented in clinical trials,[61,62] despite data that older women with breast cancer and younger postmenopausal patients derive similar benefits from treatment.[63,64] However, some elders may be unable to tolerate the toxicity and stress associated with cancer therapy. Frail elders with breast cancer are a challenging group. Geriatric assessment can help identify frail patients and suggest useful interventions. Nevertheless, most frail patients are still likely to have a shortened survival that minimizes the benefits of standard therapies.
The increasing numbers of older adults with a cancer diagnosis demand that oncologists prepare themselves to mange the challenges of the frail older cancer patient. In particular, skills to appropriately target the intensity of interventions, to identify complicating factors, and to prevent toxicity and institute supportive care where appropriate are needed. Balducci has suggested that several questions be considered prior to making treatment decisions: Will the patient die of cancer or with cancer? Will the patient suffer the complications of cancer during his/her lifetime? Is the patient able to tolerate the treatment of cancer? Is palliation appropriate? These questions help frame a treatment approach.
The National Comprehensive Cancer Network (NCCN) has put forth a treatment guideline for senior adult oncology patients. The NCCN guideline includes the Fried criteria for assessing frailty, an example of Comprehensive Geriatric Assessment, and the VES-13 as a screen for impairment. In addition to evaluating the patient, it is important to consider the effects of the patient's illness on family and friends, and to realize that the patient may be independent at the beginning of therapy but become temporarily or permanently dependent over time. A support system is necessary to assess function, monitor side effects, and assist in emergencies.
More research is needed to define frailty, identify its contributors, and develop assessment tools for the older oncology population. It is not yet clear how an abnormal finding on screening for frailty should impact cancer therapy decision-making. Future research evaluating variations in treatment intensity and best supportive care when warranted would be enhanced by a rigorous assessment of frailty and frailty risk. Assessment of frailty needs to be integrated into evaluation of response, toxicity, survival, and quality of life among elderly cancer patients.
The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Yancik R: Population aging and cancer: A cross-national concern. Cancer J 11:437-441, 2005.
2. Yancik R: Cancer burden in the aged: An epidemiologic and demographic overview. Cancer80:1273-1283, 1997.
3. Ries LAG, Melbert D, Krapcho M, et al (eds): SEER Cancer Statistics Review, 1975-2004. Bethesda, MD; National Cancer Insitiute. Based on November 2006 SEER data submission, posted to the SEER website, 2007. Available at http://seer.cancer.gov/csr/1975_2004/. Accessed Nov 11, 2007.
4. National Center for Health Statistics, United States Census Bureau. Vital Statistics of the United States. Hyattsville, MD; National Center for Health Statistics, 2001.
5. Yancik R, Ries LG, Yates JW: Breast cancer in aging women. A population-based study of contrasts in stage, surgery, and survival. Cancer 63:976-981, 1989.
6. Kimmick GG., Hughes KS, Muss HB: Breast cancer in older women, in Harris JR, Lippman ME, Morrow M, et al (eds): Diseases of the Breast, pp 1323-1338. Philadelphia, Lippincott Williams & Wilkins; 2004.
7. Ferrucci L, Guralnik JM, Studenski S, et al: Designing randomized, controlled trials aimed at preventing or delaying functional decline and disability in frail, older persons: A consensus report. J Am Geriatr Soc 52:625-634, 2004.
8. Ferrucci L, Guralnik JM, Cavazzini C, et al: The frailty syndrome: A critical issue in geriatric oncology. Crit Rev Oncol Hematol 46:127-137, 2003.
9. Cohen HJ: In search of the underlying mechanisms of frailty. J Gerontol A Biol Sci Med Sci 55:M706-M708, 2000.
10. Fried LP, Tangen CM, Walston J, et al: Frailty in older adults: Evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56:M146-M156, 2001.
11. Fried LP, Kronmal RA, Newman AB, et al: Risk factors for 5-year mortality in older adults: The Cardiovascular Health Study. JAMA 279:585-592, 1998.
12. Fried LP, Ferrucci L, Darer J, et al: Untangling the concepts of disability, frailty, and comorbidity: Implications for improved targeting and care. J Gerontol A Biol Sci Med Sci 59:255-263, 2004.
13. Balducci L: Geriatric oncology: Challenges for the new century. Eur J Cancer 36:1741-1754, 2000.
14. Fried LP, Walston J: Frailiy and failure to thrive, in Hazzard WR, Blass JP, Ettinger WH, et al (eds): Principles of Geriatric Medicine and Geontology pp 1387-1402. New York, McGraw-Hill, 1999.
15. Rodin MB, Mohile SG: A practical approach to geriatric assessment in oncology. J Clin Oncol 25:1936-1944, 2007.
16. Hurria A, Cleary TA, Adelman RD: Cancer in the frail elderly, in Muss HB, Hunter C, Johnson KA (eds): Treatment and Management of Cancer in the Elderly, pp 539-557. New York, Taylor & Francis, 2006.
17. Muss HB, Woolf S, Berry D, et al: Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 293:1073-1081, 2005.
18. Muss HB, Berry DA, Cirrincione C, et al: Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: The Cancer and Leukemia Group B experience. J Clin Oncol 25:3699-3704, 2007.
19. Guralnik JM, Simonsick EM, Ferrucci L, et al: A short physical performance battery assessing lower extremity function: Association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 49:M85-M94, 1994.
20. Abate M, Diloria A DiRenzo D, et al: Fraility in the elderly: The physical dimension. Europa Medicophysica 42:1-9, 2006.
21. Baumgartner RN, Wayne SJ, Waters DL, et al: Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly. Obes Res 12:1995-2004, 2004.
22. Janssen I: Influence of sarcopenia on the development of physical disability: The Cardiovascular Health Study. J Am Geriatr Soc 54:56-62, 2006.
23. Visser M, Goodpaster BH, Kritchevsky SB, et al: Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. J Gerontol A Biol Sci Med Sci 60:324-333, 2005.
24. Ferrucci L, Corsi A, Lauretani F, et al: The origins of age-related proinflammatory state. Blood 105:2294-2299, 2005.
25. Walston J, McBurnie MA, Newman A, et al: Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: Results from the Cardiovascular Health Study. Arch Intern Med 162:2333-2341, 2002.
26. Mitnitski AB, Song X, Rockwood K: The estimation of relative fitness and frailty in community-dwelling older adults using self-report data. J Gerontol A Biol Sci Med Sci 59:M627-M632, 2004.
27. Satariano WA, Ragland DR: The effect of comorbidity on 3-year survival of women with primary breast cancer. Ann Intern Med 120:104-110, 1994.
28. Satariano WA: Aging, comorbidity, and breast cancer survival: An epidemiologic view. Adv Exp Med Biol 330:1-11, 1993.
29. Bergman L, Dekker G, van Leeuwen FE, et al: The effect of age on treatment choice and survival in elderly breast cancer patients. Cancer 67:2227-2234, 1991.
30. Maas HA, Janssen-Heijnen ML, Olde Rikkert MG, et al: Comprehensive geriatric assessment and its clinical impact in oncology. Eur J Cancer 43:2161-2169, 2007.
31. Inouye SK, Studenski S, Tinetti ME, et al: Geriatric syndromes: Clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc 55:780-791, 2007.
32. Hurria A, Lachs MS, Cohen HJ, et al: Geriatric assessment for oncologists: Rationale and future directions. Crit Rev Oncol Hematol 59:211-217, 2006.
33. Karnofsky DA: Determining the extent of the cancer and clinical planning for cure. Cancer 22:730-734, 1968.
34. Walston J, Hadley EC, Ferrucci L, et al: Research agenda for frailty in older adults: Toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc 54:991-1001, 2006.
35. Balducci L: The geriatric cancer patient: Equal benefit from equal treatment. Cancer Control 8:1-25, 2001.
36. Monfardini S, Ferrucci L, Fratino L, et al: Validation of a multidimensional evaluation scale for use in elderly cancer patients. Cancer 77:395-401, 1996.
37. Repetto L, Fratino L, Audisio RA, et al: Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: An Italian Group for Geriatric Oncology Study. J Clin Oncol 20:494-502, 2002.
38. Balducci L, Extermann M: Management of cancer in the older person: A practical approach. Oncologist 5:224-237, 2000.
39. Hurria A, Gupta S, Zauderer M, et al: Developing a cancer-specific geriatric assessment: A feasibility study. Cancer 104:1998-2005, 2005.
40. Saliba D, Elliott M, Rubenstein LZ, et al: The Vulnerable Elders Survey: A tool for identifying vulnerable older people in the community. J Am Geriatr Soc 49:1691-1699, 2001.
41. Mohile SG, Bylow K, Dale W, et al: A pilot study of the vulnerable elders survey-13 compared with the comprehensive geriatric assessment for identifying disability in older patients with prostate cancer who receive androgen ablation. Cancer 109:802-810, 2007.
42. Gill TM, Gahbauer EA, Allore HG, et al: Transitions between frailty states among community-living older persons. Arch Intern Med 166:418-423, 2006.
43. Singh MA: Exercise comes of age: rationale and recommendations for a geriatric exercise prescription. J Gerontol A Biol Sci Med Sci 57:M262-M282, 2002.
44. Leveille SG, Guralnik JM, Ferrucci L, et al: Aging successfully until death in old age: opportunities for increasing active life expectancy. Am J Epidemiol 149:654-664, 1999.
45. Landi F, Cesari M, Onder G, et al: Physical activity and mortality in frail, community-living elderly patients. J Gerontol A Biol Sci Med Sci 59:833-837, 2004.
46. Barry BK, Carson RG: The consequences of resistance training for movement control in older adults. J Gerontol A Biol Sci Med Sci 59:730-754, 2004.
47. Taaffe DR: Sarcopenia—exercise as a treatment strategy. Aust Fam Physician 35:130-134, 2006.
48. Latham NK, Bennett DA, Stretton CM, et al: Systematic review of progressive resistance strength training in older adults. J Gerontol A Biol Sci Med Sci 59:48-61, 2004.
49. Seynnes O, Fiatarone Singh MA, et al: Physiological and functional responses to low-moderate versus high-intensity progressive resistance training in frail elders. J Gerontol A Biol Sci Med Sci 59:503-509, 2004.
50. Extermann M, Meyer J, McGinnis M, et al: A comprehensive geriatric intervention detects multiple problems in older breast cancer patients. Crit Rev Oncol Hematol 49:69-75, 2004.
51. Arnoldi E, Dieli M, Mangia M, et al: Comprehensive geriatric assessment in elderly cancer patients: An experience in an outpatient population. Tumori 93:23-25, 2007, 2007.
52. McCorkle R, Strumpf NE, Nuamah IF, et al: A specialized home care intervention improves survival among older post-surgical cancer patients. J Am Geriatr Soc 48:1707-1713, 2000.
53. Akhtar SS, Allan SG, Rodger A, et al: A 10-year experience of tamoxifen as primary treatment of breast cancer in 100 elderly and frail patients. Eur J Surg Oncol 17:30-35, 1991.
54. Smith I, Dowsett M, on behalf of the IMPACT Trialists: Comparison of anastrozole versus tamoxifen alone and in combination as neoadjuvant treatment of ER+ operable breast cancer in postmenopausal women: The IMPACT Trial. Presented at the Annual San Antonio Breast Cancer Symposium; San Antonio Tex; 2004.
55. Smith IE, Dowsett M: Aromatase inhibitors in breast cancer. N Engl J Med 348:2431-2442, 2003.
56. Smith IE, Dowsett M, Ebbs SR, et al: Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol 23:5108-5116, 2005.
57. Ellis MJ, Coop A, Singh B, et al: Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor- positive primary breast cancer: Evidence from a phase III randomized trial. J Clin Oncol 19:3808-3816, 2001.
58. Group: Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 365:1687-1717, 2005.
59. Witherby SM, Muss HB: Special issues related to breast cancer adjuvant therapy in older women. Breast 14:600-611, 2005.
60. Vogel CL, Cobleigh MA, Tripathy D, et al: Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719-726, 2002.
61. Hutchins LF, Unger JM, Crowley JJ, et al: Underrepresentation of patients 65 years of age or older in cancer- treatment trials. N Engl J Med 341:2061-2067, 1999.
62. Sateren WB, Trimble EL, Abrams J, et al: How sociodemographics, presence of oncology specialists, and hospital cancer programs affect accrual to cancer treatment trials. J Clin Oncol 20:2109-2117, 2002.
63. Muss HB, Woolf S, Berry D, et al: Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 293:1073-1081, 2005.
64. Christman K, Muss HB, Case LD, et al: Chemotherapy of metastatic breast cancer in the elderly. The Piedmont Oncology Association experience JAMA 268:57-62, 1992.
65. Katz S, Ford AB, Moskowitz RW, et al: Studies of illness in the aged. The index of ADL: A standardized measure of biological and psychosocial function. JAMA 185:914-919, 1963.
66. Lawton MP, Brody EM: Assessment of older people: Self-maintaining and instrumental activities of daily living. Gerontologist 9:179-186, 1969.