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Originally published as JCO Early Release 10.1200/JCO.2003.05.083 on August 11 2003 © 2003 American Society for Clinical Oncology
What Constitutes Optimal Care for Older Women With Breast Cancer?Department of Medicine, Boston University School of Medicine, Department of Epidemiology, Boston University School of Public Health, Boston, MA
AN ESTIMATED 203,500 women were diagnosed with breast cancer in 2002, with almost half of the cases occurring in women Although available age-specific clinical trials data demonstrate that treatment efficacy is not modified by age,3–5 this efficacy evidence is limited by the lack of inclusion of substantial numbers of older women, particularly those of advanced age and those with comorbidities. As a result, there is considerable controversy about what constitutes appropriate cancer care for older women with newly diagnosed breast cancer. This controversy is reflected in the persistence of age-dependent variations in care over time, with older women being less likely to receive definitive care for a new diagnosis of breast cancer.6–21
There would be little cause for concern if these age-dependent variations in care had no affect on outcomes.22 Although breast cancer-specific mortality rates have declined among women younger than 70 years old, they are either stable (in women 70 to 79 years old) or have increased (in women In this issue of the Journal of Clinical Oncology, Bouchardy et al25 address the relationship between undertreatment of breast cancer and breast cancer mortality in a cohort of women 80 years of age and older diagnosed and treated in the Canton of Geneva, Switzerland. The fact that there were only 407 breast cancer patients in this age group diagnosed over an 11-year period highlights one of the challenges of this research. In comparison to such age-related diseases as heart disease, breast cancer is relatively uncommon in old age, although breast cancer incidence in this age group is still substantial (477.8 per 100,000 population in women 80 to 84 years of age and 401.7 per 100,000 population in women 85 years of age and older26). For their study, Bouchardy et al25 used tumor registry data that included sociodemographic, comorbidity, tumor, and treatment characteristics, and systematically collected date and cause of death. Herein lies a second challenge of this kind of research: missing data were a particular problem, with absence of data on key variables, ranging from 20% for comorbidity, 49% for tumor grade, and 74% for estrogen receptor status.25 Because these are all important prognostic factors, their absence created important difficulties for multivariable adjustments, including incomplete control for confounding and decreased power and precision. This is illustrated in the regression models relating treatment to mortality (Table 3 in Bouchardy et al25). Here, mastectomy plus adjuvant therapy and breast-conserving surgery plus adjuvant therapy both appear to protect against death from causes other than breast cancer. This suggests residual confounding, either because comorbidity was not well measured or because undertreatment of breast cancer is associated with undertreatment of other medical conditions. Furthermore, an important question is whether this sample of older Swiss women with breast cancer differs in important ways when compared with women of comparable age elsewhere in the world. In this sample, the average tumor size was 30 mm, and only 22% presented with stage I or in situ disease (64% presented with stage I or II disease). As noted above, tumor grade was missing for 49% and estrogen receptor status was missing for 74% of the sample. Twelve percent received no therapy and an additional 32% received tamoxifen alone. Among comparably aged women identified through the Surveillance, Epidemiology, and End Results (SEER) program in the United States from 1990 through 1996, median tumor size was 19 mm (mean, 23.6 mm) and 45% were diagnosed with stage I or in situ disease (74% with stage I or II disease). Histologic grade was missing for 41% and estrogen receptor status was missing for 37% of the sample.27 Among those in each sample with known histologic grade and estrogen receptor status, the SEER sample has a higher proportion of poorly differentiated tumors than the Geneva sample (38% v 23%), but a slightly lower proportion of estrogen receptor–negative tumors (15% v 19%). SEER does not completely capture administration of chemotherapy and hormonal therapy, but of 12,891 women 80 years of age and older who were newly diagnosed with breast cancer, 14% received neither surgery nor radiation therapy. Together, these data indicate that the Geneva sample differs from the US SEER sample with respect to stage and tumor size—more women had later stage and larger tumors in the Geneva sample—but that among those for whom data are available, US women in this age group have a higher proportion of poorly differentiated tumors, further emphasizing that breast cancer is not an indolent disease in many older women.
Despite this study’s limitations, it joins a growing number of observational studies that link undertreatment of breast cancer to higher rates of breast cancer recurrence and mortality.28–32 Although appropriately criticized for their methodologic shortcomings (including lack of detailed information about comorbidities and systemic adjuvant therapies, and inability to control completely for both known and unknown confounders), these studies provide the best data that we have regarding the relationship between treatment and outcome, in part because older women are poorly represented in clinical trials. Even with the elimination of upper age limits for cancer clinical trial participation, older persons remain substantially underrepresented.33–35 Among cooperative group clinical trials sponsored by the National Cancer Institute for early stage breast cancer, women In the absence of substantial clinical trial data and given the prospect that few will be available in the foreseeable future, we assert that carefully conducted observational studies that use all available strategies to minimize or quantify the effects of confounding and bias will provide important evidence for clinical decision making to guide the design of future studies.37 Although there continues to be a vigorous discussion in the medical literature regarding the advantages and disadvantages of observational versus randomized clinical trial evidence,38–40 we and others38–40 believe that randomized clinical trials and observational studies have complementary roles, particularly when external validity, feasibility, and ethical concerns are paramount, as in the case of older women with early-stage breast cancer. Although patients’ health status,7,9,12,17–20 patient and family preferences and support,11,17,19,41,42 and patient-physician interactions9,17,43,44 explain, in part, age-related treatment variations, age alone remains an independent risk factor for less than definitive breast cancer care. It is likely to remain so until there are adequate data to support one treatment strategy over another for older women with early-stage disease. AUTHOR’S DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST The author indicated no potential conflicts of interest. REFERENCES 1. American Cancer Society: Cancer Facts & Figures 2002. Atlanta, GA, American Cancer Society, 2003 2. National Center for Health Statistics: Life Tables of the United States, 1997. http://www.cdc.gov/nchs/datawh/statab/unpubd/mortabs/lewk3.htm
3. Clark RM, Whelan T, Levine M, et al: Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: An update. J Natl Cancer Inst 88:1659–1664, 1996
4. Fisher B, Dignam J, Wolmark N, et al: Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst 89:1673–1682, 1997 5. Early Breast Cancer Trialists’ Collaborative Group: Tamoxifen for early breast cancer: An overview of the randomised trials. Lancet 351:1451–1467, 1998[CrossRef][Medline] 6. Allen C, Cox ED, Manton KG, et al: Breast cancer in the elderly: Current patterns of care. J Am Geriatr Soc 34:637–642, 1986[Medline] 7. Greenfield S, Blanco DM, Elashoff RM, et al: Patterns of care related to age of breast cancer patients. JAMA 257:2766–2770, 1987[Abstract] 8. Chu J, Diehr P, Feigl P, et al: The effect of age on the care of women with breast cancer in community hospitals. J Gerontol 42:185–190, 1987[Medline] 9. Silliman RA, Guadagnoli E, Weitberg AB, et al: Age as a predictor of diagnostic and initial treatment intensity in newly diagnosed breast cancer patients. J Gerontol 44:46–50, 1989 10. 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[CrossRef][Medline] 11. Lazovich D, White E, Thomas DB, et al: Underutilization of breast-conserving surgery and radiation therapy among women with stage I or II breast cancer. JAMA 266:3433–3438, 1991[Abstract]
12. Ballard-Barbash R, Potosky AL, Harlan LC, et al: Factors associated with surgical and radiation therapy for early stage breast cancer in older women. J Natl Cancer Inst 88:716–726, 1996 13. Busch E, Kemeny M, Fremgen A, et al: Patterns of breast cancer care in the elderly. Cancer 78:101–111, 1996[CrossRef][Medline] 14. Newschaffer CJ, Penberthy L, Desch CE, et al: The effect of age and comorbidity in the treatment of elderly women with nonmetastatic breast cancer. Arch Intern Med 156:85–90, 1996[Abstract] 15. Hilner BE, Penberthy L, Desch CE, et al: Variation in staging and treatment of local and regional breast cancer in the elderly. Breast Cancer Res Treat 40:75–86, 1996[CrossRef][Medline] 16. Wanebo H, Cole B, Chung M, et al: Is surgical management compromised in elderly patients with breast cancer? Ann Surg 225:579–589, 1997[CrossRef][Medline] 17. Silliman RA, Troyan SL, Guadagnoli E, et al: The impact of age, marital status, and physician-patient interactions on the care of older women with breast cancer. Cancer 80:1326–1334, 1997[CrossRef][Medline] 18. Hebert-Croteau N, Brisson J, Latreille J, et al: Compliance with consensus recommendations for the treatment of early stage breast carcinoma in elderly women. Cancer 85:1104–1113, 1999[CrossRef][Medline] 19. Mandelblatt JS, Hadely J, Kerner JF, et al: Patterns of breast carcinoma treatment in older women: Patient preference and clinical and physician influences. Cancer 89:561–573, 2000[CrossRef][Medline]
20. Yancik R, Wesley MN, Ries LAG, et al: Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA 285:885–892, 2001
21. Morrow M, White J, Moughan J, et al: Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma. J Clin Oncol 19:2254–2262, 2001 22. Silliman RA, Lash TL: Do variations in breast cancer care matter? Med Care 40:177–180, 2002[CrossRef][Medline]
23. Chu KC, Tarone RE, Kessler LG, et al: Recent trends in US breast cancer incidence, survival, and mortality rates. J Natl Cancer Inst 88:1571–1579, 1996 24. American Cancer Society: Breast Cancer Facts & Figures 2001–2002: American Cancer Society, 2001. http://www.cancer.org
25. Bouchardy C, Rapiti E, Fioretta G, et al: Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol 21:3580–3587, 2003 26. Ries LA, Eisner MP, Kosary CL, et al, eds: SEER Cancer Statistics Review, 1975–2000. Bethesda, MD, National Cancer Institute, 2003. http://seer.cancer.gov/csr/1975-2000 27. National Cancer Institute: SEER 1973–2000 Public-Use Data. http://seer.cancer.gov/publicdata/ 28. Cerrotta A, Lozza L, Kenda R, et al: Current controversies in the therapeutic approach to early breast cancer in the elderly. RAYS 22:66–68, 1997 (suppl)[Medline]
29. Goodwin JS, Samet JM, Hunt WC: Determinants of survival in older cancer patients. J Natl Cancer Inst 88:1031–1038, 1996 30. Lee-Feldstein A, Anton-Culver H, Feldstein PJ: Treatment differences and other prognostic factors related to breast cancer survival: Delivery systems and medical outcomes. JAMA 271:1163–1168, 1994[Abstract] 31. Lash T, Silliman RA, Guadagnoli E, et al: The effect of less than definitive care on breast cancer recurrence and mortality. Cancer 89:1739–1747, 2000[CrossRef][Medline] 32. Du X, Freeman J, Nattinger AB, et al: Survival of women after breast conserving surgery for early stage breast cancer. Breast Cancer Res Treat 72:23–31, 2002[CrossRef][Medline]
33. 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
34. Lewis JH, Kilgore ML, Goldman DP, et al: Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol 21:1383–1389, 2003
35. Yee KWL, Pater JL, Pho L, et al: Enrollment of older patients in cancer treatment trials in Canada: Why is age a barrier? J Clin Oncol 21:1618–1623, 2003
36. Kemeny MM, Peterson BL, Kornblith AB, et al: Barriers to clinical trial participation by older women with breast cancer. J Clin Oncol 21:2268–2275, 2003
37. Radford MJ, Foody JM: How do observational studies expand the evidence base for therapy? JAMA 286:1228–1230, 2001
38. Barton S: Which clinical studies provide the best evidence? The best RCT still trumps the best observational study. BMJ 321:255–256, 2000
39. Ioannidis JPA, Haidich A-B, Lau J: Any casualties in the clash of randomised and observational evidence? No recent comparisons have studied selected questions, but we need more data. BMJ 322:879–880, 2001
40. Ionnidis JPA, Haidich A-B, Pappa M, et al: Comparison of evidence of treatment effects in randomized and nonrandomized studies. JAMA 286:821–830, 2001 41. Goodwin JS, Hunt WC, Key CR, et al: The effect of marital status on stage, treatment, and survival of cancer. JAMA 258:3125–3130, 1987[Abstract] 42. Ward S, Heidrick S, Wolberg W: Factors women take into account when deciding upon type of surgery for breast cancer. Cancer Nurs 12:344–351, 1989[Medline]
43. Liberati A, Apolone G, Nicolucci A, et al: The role of attitudes, beliefs, and personal characteristics of Italian physicians in the surgical treatment of early breast cancer. Am J Public Health 81:38–42, 1991 44. Silliman RA, Demissie S, Troyan SL: The care of women with early stage breast cancer: What is the role of surgeon gender? Med Care 37:1057–1067, 1999[CrossRef][Medline] This article has been cited by other articles:
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Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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65 years of age.
