|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Originally published as JCO Early Release 10.1200/JCO.2006.09.2106 on April 2 2007 © 2007 American Society of Clinical Oncology. Breast Cancer Mortality Trends in the United States According to Estrogen Receptor Status and Age at Diagnosis
From the Department of Surgery, National Naval Medical Center and Uniformed Services, University of the Health Sciences, Bethesda; and the Biostatistics Branch, Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Rockville, MD Address reprint requests to Ismail Jatoi, MD, PhD, Director of Breast Care Center, Department of Surgery, National Naval Medical Center and Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814; e-mail: ismail.jatoi{at}us.army.mil
Purpose Since 1990, overall breast cancer mortality rates in the United States decreased 24%. This decline has been attributed to mammography screening and adjuvant systemic therapy. However, the efficacy of these modalities may depend on estrogen receptor (ER) expression and age. We therefore examined breast cancer mortality trends in the United States according to ER status and age. Methods Using the Surveillance, Epidemiology, and End Results (SEER) program (1990-2003), we calculated trends in incidence-based mortality (IBM), annual hazard rates for breast cancer deaths after diagnosis, and relative hazard rates for women with ER-positive and ER-negative tumors. Relative hazard rates were assessed with Cox proportional hazards models, adjusted for stage and grade, and stratified by age at diagnosis. Results During the study period, IBM and annual hazard rates for breast cancer deaths decreased among women with ER-positive and ER-negative tumors, although declines were greater for those with ER-positive tumors. Among women younger than 70 years, relative hazard rates declined 38% for those with ER-positive tumors versus 19% for those with ER-negative tumors. Among women 70 years or older, relative hazard rates declined 14% for those with ER-positive tumors versus no significant decline for those with ER-negative tumors. Conclusion In the United States, breast cancer mortality rates have declined among women with ER-positive and ER-negative tumors, with greater declines among younger women and those with ER-positive tumors. Although mortality in all groups remains unacceptably high, additional emphasis should be placed on improving outcomes of breast cancer patients older than 70 years and those of all ages with ER-negative tumors.
Breast cancer mortality in the United States peaked in 1989 with an age-adjusted (2000 United States standard) mortality rate of 33 per 100,000 woman-years.1 Thereafter, mortality rates declined 24% to 25 per 100,000 woman-years in 2003. Mathematical models and clinical trial results suggest that mammography screening and adjuvant systemic therapy are largely responsible for the overall decline in mortality.2-5 However, population-based mortality rates in subgroups of breast cancer patients have not been systematically described. Mammography screening preferentially detects indolent tumors, a disproportionate number of which are estrogen receptor (ER)-positive.6 In addition, ER status is a clinically important predictive factor, forecasting response to systemic hormone therapy as well as to chemotherapy.2,7 Age at diagnosis is another potentially important predictive factor.8,9 Therefore, we hypothesized that national trends in breast cancer mortality may vary according to ER expression and age at diagnosis, as well as other variables such as stage and grade at diagnosis. To examine breast cancer mortality trends in the United States according to these factors, we used the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) program. SEER is a consortium of regional cancer registries with meticulous and consistent data collection and standards. SEER rates are considered to be nationally representative. Using SEER, we evaluated national trends in overall mortality, trends in incidence-based mortality (IBM),10 annual hazard rates for breast cancer deaths, and relative hazard rates according to ER expression and age at diagnosis. In doing so, we hoped to elucidate how improvements in diagnosis and treatment have impacted outcomes in major populations of breast cancer patients.
Breast cancer incidence and mortality data were obtained from the National Cancer Institute's SEER program, SEER*Stat Incidence11 and Mortality databases.12 We analyzed invasive breast cancer cases in SEER's 9 Registry Database, diagnosed during the years 1990 to 2003. The 9 Registry Database included tumor registries in Atlanta, GA, Connecticut, Detroit, MI, Hawaii, Iowa, New Mexico, San Francisco-Oakland, CA, Seattle-Puget Sound, WA, and Utah. We selected only the first matching record for each SEER breast cancer case and excluded cases whose reporting sources were only from autopsy records or death certificates. Breast cancer cases were stratified by ER expression. SEER has collected ER data since 1990, but does not record the method of hormone receptor assay, although immunohistochemistry was likely used during this study period (1990 to 2003). Each SEER registry extracted ER information from the medical records and recorded ER expression as positive, negative, missing, borderline, or unknown. We combined missing, borderline, and unknown data into one group, designated as other or unknown. We excluded ER other or unknown from most analyses given that ER unknowns tend to follow ER-positive patterns (Table 1), as also shown in other studies.13,14
Tumor characteristics were categorized according to tumor size (  2.0 cm v > 2.0 cm), lymph node (LN) status (negative v positive), and histologic grades (I, II, III, and IV). Stages I, II, III, IV were defined by SEER according to the American Joint Committee on Cancer (AJCC) staging scheme third edition.15 Grade 1 consisted of the well-differentiated tumors, grade 2 was moderately differentiated tumors, grade 3 was poorly differentiated tumors, and grade 4 was undifferentiated or anaplastic.
Statistical Analysis We obtained IBM rates using SEER*Stat version 6.2.3. IBM is a statistical tool for calculating population-based mortality rates according to tumor characteristics (in this case, ER expression). IBM represents the cross-sectional mortality rate in the population as a whole for a given tumor type in a specified calendar period.10 Consequently, IBM reflects the combined impact of cancer incidence, case ascertainment, and treatment. Because ER was not recorded by SEER until 1990, all cases diagnosed before 1990 are ER unknown. Therefore, we defined IBM rates using a moving 5-year calendar period starting in 1994. For example, the IBM rate for ER-negative tumors in 1994 equaled the number of ER-negative breast cancer deaths during 1994 among women diagnosed and reported to SEER with ER-negative tumors during 1990 to 1994, divided by the corresponding population in the SEER catchment area during calendar year 1994. Similarly, IBM rates for 1995 represented deaths that year among patients diagnosed from 1991 to 1995, and so on. IBM temporal trends were assessed as annual percentage changes using weighted linear regression analysis, with the weights given by the inverse of the variance of the IBM estimators. To assess trends in breast cancer prognosis, we used spline functions to estimate ER-positive and ER-negative hazard rates for tumors diagnosed during 1990 to 2002 and followed through 2003.16 The time period 1990 to 2002 was stratified into two 4-year (1990 to 1993 and 1994 to 1997) and one 5-year time period (1998 to 2002). Hazard rate curves showed the instantaneous rate of breast cancer death in a specified time interval after initial diagnosis among women who were alive at the beginning of that time interval. We modeled hazard curves using cubic splines with joinpoints selected using Akaike's information criteria (AIC).17 We constructed 95% CIs using bootstrap resampling.18 We tested for changes over calendar periods according to ER expression, using Cox proportional hazards models.19
We also used Cox proportional hazards models to assess relative hazard rates of breast cancer deaths according to ER expression, considering both single calendar years of diagnosis from 1991 to 2002 versus 1990 and the grouped calendar years of diagnosis as defined above (ie, 1994 to 1997 and 1998 to 2002 v 1990 to 1993). Relative hazard curves were adjusted for AJCC stage (I, II, III, and IV) and tumor grade (I, II, III, IV, and unknown), and stratified by age at diagnosis (ages
Descriptive Statistics SEER's 9-registry database collected data for 234,828 invasive female breast cancer cases, newly diagnosed during the years 1990 to 2003. ER-positive tumors comprised 77% all breast cancers with known ER expression (147,289 of 190,833 cases). Age-adjusted incidence rates were 3.3-fold greater for ER-positive than for ER-negative tumors (80.2 compared with 24.0 per 100,000 woman-years). Median ages at diagnosis were 55 years, 63 years, and 65 years for ER-negative, ER-positive, and unknown status, respectively. Tumors with unknown ER expression were more like ER-positive than ER-negative breast cancers, consistent with the overall predominance of ER-positive tumors among cases with known ER status. For example, among women with ER-unknown expression, IRR for age 50 to 69 years compared with age younger than 50 was 7.6 (95% CI, 7.4 to 7.8), similar to ER-positive breast cancer (IRR, 8.5; 95% CI, 8.4 to 8.6). From 1990 to 2003, breast cancer mortality rates overall (all breast cancer cases) declined 24% from 33 to 25 per 100,000 woman years (Fig 1A). IBM rates were restricted to ER-positive and ER-negative tumors, using a moving 5-year window (Fig 1B). IBM for ER-positive tumors declined 13% from 6.1 to 5.3 per 100,000 woman-years (Fig 1B; P < .0001 for trend). IBM for ER-negative tumors fell a more modest 4% from 4.9 to 4.7 per 100,000 woman-years (P = .22 for trend).
Annual hazard rates for breast cancer mortality according to ER expression and calendar period (1990 to 1993, 1994 to 1997, and 1998 to 2002) are plotted in Figure 2. Similar to our previous report for a different study period (1992 to 2002),20 hazard rates were nonproportional according to ER expression for all three time periods. In each period, ER-negative hazard rates rose to a sharp peak of 7% to 8% per year approximately 2 years after initial breast cancer diagnosis, and then declined. In contrast, ER-positive hazard rates lacked a sharp peak but had a stable long-term rate of 1% to 2% per year. Previous studies have shown that this sharp hazard peak is also associated with other high-risk tumor characteristics, such as large tumor size, positive nodes, high grade, and negative progesterone receptors, whereas low-risk tumors (small size, negative nodes, low grade, and positive progesterone receptors) lack this peak.14,21
During the calendar periods 1990 to 1993, 1994 to 1997, and 1998 to 2002 (Fig 2), hazard curves for ER-positive cases showed substantial moderation, whereas ER-negative cases showed less improvement. For example, ER-positive hazard rates dropped 37% approximately 2 to 4 years after breast cancer diagnosis (ie, falling from 2.7% per year among cases diagnosed during 1990 to 1993 to 1.7% per year among cases diagnosed during 1998 to 2002). In contrast, ER-negative hazard rates declined a more modest 11% at the 18-month landmark (ie, dropping from 7.9% per year among cases diagnosed during 1990 to 1993% to 7% per year among cases diagnosed during 1998 to 2002). Overall, hazard rate declines were statistically significant for both ER-positive tumors (P < .0001) and ER-negative tumors (P = .0014).
Figures 3 shows the relative hazard rates according to ER expression and age at diagnosis (age
Relative hazard trends according to age at diagnosis also differed for ER-positive and ER-negative tumors (Figs 3C and 3D and Table 2) . Among women younger than 70 years (ages 50 to 69 and 49 years; Figs 3C and 3D), relative hazard rates declined 38% for ER-positive tumors (Table 2, weighted average relative hazard = 0.62; 95% CI, 0.58 to 0.67) versus 19% for ER-negative tumors (Table 2, weighted average relative hazard = 0.81; 95% CI, 0.75 to 0.86). Among women  70 years, relative hazard rates declined 14% for ER-positive tumors (relative hazard rate = 0.86; 95% CI, 0.79 to 0.94) versus no decline for ER-negative tumors (relative hazard rate = 0.93; 95% CI, 0.83 to 1.06).
Breast cancer mortality rates overall in the United States have declined significantly since 1990. In that year, SEER began to collect data on the ER status of newly diagnosed breast cancer cases. Our analyses indicate that since 1990, women with ER-positive tumors have experienced greater declines in breast cancer mortality than those with ER-negative tumors. Furthermore, breast cancer-specific mortality has declined more among women diagnosed at ages younger than 70 compared with older women. Specifically, among women diagnosed with ER-positive breast cancer younger than 70 years, mortality from breast cancer fell 38% from 1990 to 1993 to 1998 to 2002. In contrast, mortality rates fell a more modest 14% among women diagnosed with ER-positive breast cancer who were 70 years (ie, a 2.7-fold difference compared with younger women).
In addition, there has been some improvement in the prognosis of women with ER-negative tumors, though less than for those patients with ER-positive tumors. Again, improvements in the prognosis of women with ER-negative tumors varied according to age at diagnosis. In women diagnosed with ER-negative breast cancers who were younger than 70 years, mortality rates fell 19% from 1990 to 1993 to 1998 to 2002. In contrast, there was no significant decline in the mortality rates among women diagnosed with ER-negative tumors who were We also considered secular trends in IBM rates, which complemented the relative hazard-based analyses described herein. IBM rates reflect not only population-based improvements in diagnosis and treatment, but also changes in incidence and case ascertainment. Using this approach, we confirmed a statistically significant decline for ER-positive but not ER-negative breast cancers (Fig 1B). This decrease was identified despite the fact that the incidence of ER-positive tumors (and, to a lesser extent, ER-negative tumors) artificially increased during the study period due to a shift of ER-unknown to ER-positive and/or ER-negative tumors. Indeed, rates for ER unknown patients decreased 60%, from 36.6 to 14.5 per 100,000 woman-years. Were it not for this shift, declines in IBM might have been even greater than reported in our study. Furthermore, we calculated the annual hazard of breast cancer death among cohorts of women diagnosed during 1990 to 2002 and followed through 2003 (Fig 2). For any given patient, these hazard curves provide an estimate of the risk of breast cancer death at specific time periods after diagnosis.21 These curves depict not only how the risk of death changes over time after initial diagnosis but also the magnitude of that risk. Thus, Figure 2 indicates that there have been reductions in the annual risk of death for women with both ER-negative and ER-positive tumors since 1990; although reductions have been substantially greater for those patients with ER-positive tumors. The peak in the risk of breast cancer death occurs about 2 to 4 years after initial diagnosis, and the magnitude of that peak is far greater for women with ER-negative than ER-positive tumors. Interestingly, hazard curves cross for ER-negative and ER-positive tumors approximately 6 to 8 years after diagnosis, which has important implications for counseling patients. That is, patients with ER-negative tumors are at much greater risk of recurrence and death during the early years after diagnosis, whereas patients with ER-positive tumors have a fairly consistent long-term risk of breast cancer death. In the United States, mammography screening and adjuvant systemic therapy were widely implemented in the 1980s, and increasingly utilized throughout the 1990s.22,23 Recent studies suggest that these interventions are largely responsible for the declines in breast cancer mortality rates.2,4 If this is indeed the case, then our results might suggest that mammography screening and adjuvant systemic therapy combined have been more effective for patients with ER-positive tumors than those with ER-negative tumors, and more effective among younger than older women. There were eight randomized controlled trials that examined the efficacy of mammography screening, and meta-analyses of these trials indicate that screening reduces breast cancer mortality by approximately 25%.24 However, it is not known if women with ER-positive and ER-negative tumors benefit equally from screening. Yet, mammography screening is subject to length bias, which refers to the fact that it preferentially detects slower growing tumors that exist for a longer period of time in the preclinical phase.25 Thus, cancers detected by screening tend to have favorable biologic characteristics and a disproportionate number are ER positive, while aggressive cancers are more likely to be detected in the intervals between screening sessions (as symptomatic cases), and tend to be ER negative.6,26,27 Thus, the greater decline in breast cancer mortality among women with ER-positive tumors might at least partly be due to earlier detection with mammography screening. In the 1980s, several large trials demonstrated the efficacy of adjuvant systemic therapy in reducing breast cancer mortality.28,29 The National Institutes of Health held its first consensus conference on this topic in 1985, and recommended multiagent adjuvant chemotherapy for the treatment of lymph node-positive, ER-negative breast cancer and tamoxifen for postmenopausal women with ER-positive tumors.30 Subsequently, indications for the use of adjuvant chemotherapy and tamoxifen were expanded, after clinical trials showed that almost all groups of breast cancer patients benefited from some form of adjuvant systemic therapy.31 Although the SEER database does not contain information on use of adjuvant systemic therapies, there is evidence to suggest that tamoxifen has played a particularly important role in fueling the overall decline in breast cancer mortality.2,4,5 Indeed, the efficacy of tamoxifen in premenopausal ER-positive patients was first reported at the 1995 Oxford overview meeting,32 and the sharp decline in the relative hazard mortality from 1995 onward in these patients (Fig 3C) might therefore at least partly be due to tamoxifen.
The results of our study also indicate that breast cancer mortality has not declined as much for women There is also compelling evidence to suggest that the administration of adjuvant chemotherapy in older women can significantly reduce breast cancer mortality.9 Thus, it is somewhat surprising that declines in breast cancer mortality rates were not evident among older women with ER-negative tumors in this population-based study. There might be at least three important reasons for this finding. First, in the general population, the elderly are less likely to undergo screening or receive adjuvant systemic treatment, thereby worsening their overall prognosis.35,36 Second, older patients are under-represented in clinical trials, so their optimal treatment is generally not well-established.37,38 Finally, novel adjuvant therapeutic agents, such as paclitaxel, have only recently been implemented in the treatment of primary breast cancer,2,7 and perhaps have not yet had an impact on population-based trends in mortality. A major drawback of our study is that it is descriptive, and we can only speculate as to why breast cancer mortality trends have differed among women with ER-positive and ER-negative tumors. Although we suggest that mammography screening and adjuvant systemic therapy largely account for the disparity, other unknown factors might also have played a role. Furthermore, this study is based on surveillance data, which has important limitations. For example, in the SEER data set, the measurement of hormone receptor expression was not standardized, there was incomplete or missing data on ER status, and the method of breast cancer diagnosis and treatment was not recorded. These limitations should be carefully considered because they could potentially have influenced the results of this study. Nonetheless, population-based statistics represent the best summary measure of progress in the fight against breast cancer. Clearly, most breast cancer patients seem to have benefited from recent innovations, although the mortality in all groups remains unacceptably high. In the years ahead, additional emphasis should be placed on women with ER-negative tumors and the elderly, and larger numbers of these patients should be recruited into targeted clinical trials.
The authors indicated no potential conflicts of interest.
Conception and design: Ismail Jatoi, William F. Anderson, Philip S. Rosenberg Collection and assembly of data: Bingshu E. Chen Data analysis and interpretation: Ismail Jatoi, Bingshu E. Chen, William F. Anderson, Philip S. Rosenberg Manuscript writing: Ismail Jatoi, Bingshu E. Chen, William F. Anderson, Philip S. Rosenberg Final approval of manuscript: Ismail Jatoi, Bingshu E. Chen, William F. Anderson, Philip S. Rosenberg
published online ahead of print at www.jco.org on April 2, 2007. Supported in part by the intramural research program of the National Institutes of Health and the National Cancer Institute. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. Ries LAG, Harkins D, Krapcho M, et al: SEER Cancer Statistics Review, 1975-2003. National Cancer Institute, 2006 2. Early Breast Cancer Trialists’ Collaborative 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[CrossRef][Medline] 3. Jatoi I, Miller AB: Why is breast-cancer mortality declining? Lancet Oncol 4:251-254, 2003[CrossRef][Medline] 4. Berry DA, Cronin KA, Plevritis SK, et al: Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 353:1784-1792, 2005 5. Cronin KA, Mariotto AB, Clarke LD, et al: Additional common inputs for analyzing impact of adjuvant therapy and mammography on U.S. mortality. J Natl Cancer Inst Monogr 26-29, 2006 6. Narod SA, Dube MP: Biologic characteristics of interval and screen-detected breast cancers. J Natl Cancer Inst 93:151-152, 2001 7. Berry DA, Cirrincione C, Henderson IC, et al: Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295:1658-1667, 2006 8. Schott A, Hayes DF: Adjuvant chemotherapy for elderly women with hormone receptor-positive breast cancer: An old(er) problem. J Clin Oncol 22:4660-4662, 2004 9. 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 10. Chu KC, Miller BA, Feuer EJ, et al: A method for partitioning cancer mortality trends by factors associated with diagnosis: An application to female breast cancer. J Clin Epidemiol 47:1451-1461, 1994[CrossRef][Medline] 11. SEER: Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence-SEER 9 Regs Public-use, Nov 2004 sub (1973-2003), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2006, based on November 2005 submission, 2006 12. SEER: Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Mortality - All COD, Public-Use With State, Total U.S. (1969-2003), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2006. Underlying mortality data provided by NCHS (www.cdc.gov/nchs), 2006 13. Anderson WF, Althuis MD, Brinton LA, et al: Is male breast cancer similar or different than female breast cancer? Breast Cancer Res Treat 83:77-86, 2004[CrossRef][Medline] 14. Anderson WF, Jatoi I, Devesa SS: Distinct breast cancer incidence and prognostic patterns in the NCI's SEER program: Suggesting a possible link between etiology and outcome. Breast Cancer Res Treat 90:127-137, 2005[CrossRef][Medline] 15. SEER: Breast AJCC/UICC stage. SEER Program: Comparative Staging Guide for Cancer, Major Cancer Sites 1.1, 2006, http://seer.cancer.gov/manuals/historic/comp_stage1.1.pdf 16. Rosenberg PS: Hazard function estimation using B-splines. Biometrics 51:874-887, 1995[CrossRef][Medline] 17. Akaike H: Information theory and an extension of the maximum likelihood principle, in Petrov BN, Csaki F (eds): 2nd International Symposium on Information Theory. Budapest, Akademiai Kiado, 1973, pp 267-281 18. Efron B: The jackknife, the bootstrap, and other resampling plans. Philadelphia, Society for Industrial and Applied Mathematics, 1982 19. Cox DR: Regression models and life-tables. J Royal Stat Soc B 34:187-220, 1972 20. Anderson WF, Chen BE, Jatoi I, et al: Effects of estrogen receptor expression and histopathology on annual hazard rates of death from breast cancer after primary diagnosis. Breast Cancer Res Treat 100:121-126, 2006[CrossRef][Medline] 21. Jatoi I, Tsimelzon A, Weiss H, et al: Hazard rates of recurrence following diagnosis of primary breast cancer. Breast Cancer Res Treat 89:173-178, 2005[CrossRef][Medline] 22. Ghafoor A, Jemal A, Ward E, et al: Trends in breast cancer by race and ethnicity. Ca J Clin 53:342-355, 2004 23. Mariotto A, Feuer EJ, Harlan LC, et al: Trends in use of adjuvant multi-agent chemotherapy and tamoxifen for breast cancer in the United States: 1975-1999. J Natl Cancer Inst 94:1626-1634, 2002 24. Humphrey LL, Helfand M, Chan BK, et al: Breast cancer screening: A summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 137:347-360, 2002 25. Jatoi I, Anderson WF: Cancer screening. Curr Probl Surg 42:620-682, 2005[CrossRef][Medline] 26. Klemi PJ, Toikkanen S, Rasanen O, et al: Mammography screening interval and the frequency of interval cancers in a population-based screening. Br J Cancer 75:762-766, 1997[Medline] 27. Anderson WF, Jatoi I, Devesa SS: Assessing the impact of screening mammography: Breast cancer incidence and mortality rates in Connecticut (1943-2002). Breast Cancer Res Treat 99:333-340, 2006[CrossRef][Medline] 28. Controlled trial of tamoxifen as adjuvant agent in management of early breast cancer: Interim analysis at four years by Nolvadex Adjuvant Trial Organisation. Lancet 1:257-261, 1983[Medline] 29. Henderson IC: Adjuvant systemic therapy for early breast cancer. Curr Probl Cancer 11:125-207, 1987[Medline] 30. National Institutes of Health Consensus Development Conference Statement: Adjuvant chemotherapy for breast cancer: September 9-11, 1985. CA Cancer J Clin 36:42-47, 1986 31. National Institutes of Health Consensus Development Conference Statement: Adjuvant therapy for breast cancer, November 1-3, 2000. J Natl Cancer Inst Monogr 5-15, 2001 32. Horton J: 1995 Oxford breast cancer overview: Preliminary outcomes. Cancer Control 3:78-79, 1996[Medline] 33. 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[CrossRef][Medline] 34. Centers for Disease Control: Life tables. ftp:ftp.cdc.gov/pub/Health_Statistics/NCHS/Publications/NVSR/54_14/ 35. 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 36. Witherby SM, Muss HB: Update in medical oncology for older patients: Focus on breast cancer: Management of early breast cancer. Cancer J 11:506-517, 2005[Medline] 37. 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 38. Hillner BE, Mandelblatt J: Caring for older women with breast cancer: Can observational research fill the clinical trial gap? J Natl Cancer Inst 98:660-661, 2006 Submitted September 15, 2006; accepted February 6, 2007.
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
