© 2004 by Oxford University Press
© 2004 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Breast-Conserving Surgery With or Without Radiotherapy: Pooled-Analysis for Risks of Ipsilateral Breast Tumor Recurrence and Mortality
Affiliations of authors: University of New Mexico, Cancer Research and Treatment Center, Albuquerque, NM (MR, CV); Oncology Center, Vrije Universiteit Brussel, Jette, Belgium (GS, JVDS, VVH); University of Saskatchewan, Saskatoon, SK, Canada (PT); Gynecologic Oncology and Senology, Geneva, Switzerland (GV); Surgical Pathology, Bács-Kiskun County Teaching Hospital, Kecskemét, Hungary (GC)
Correspondence to: Vincent Vinh-Hung, MD, Oncology Center, Academic Hospital, Vrije Universiteit Brussel, 101 Laarbeeklaan, 1090 Jette, Belgium (e-mail: conrvhgv{at}az.vub.ac.be)
Kunkler et al. address an important issue: whether or not to continue randomized trials of postoperative radiotherapy after breast-conserving surgery in selected patient subgroups such as those in the Scottish Post-operative Radiotherapy In Minimum-risk Elderly II (PRIME II) and the Italian RT 55-75 trials (1). We welcome the opportunity to analyze the additional data that the PRIME II and the RT 55-75 trials will provide because we think these data will help patients make the best treatment choices.
In 2003, the updated report (2) from the 2001 Cancer and Leukemia Group B (CALGB) 9343 trial (3) provided insight into several age-related issues. One issue is that the extreme difficulty in following up older patients may have led earlier studies to mistakenly conclude a lower risk of recurrence. The updated report revealed substantially improved registration of deaths and recurrences—55 deaths were reported (30 deaths with no radiotherapy, 25 deaths with radiotherapy, and a statistically nonsignificant 19% excess relative risk of mortality from omitting radiotherapy). The updated report also showed statistically significantly poorer in-breast and poorer locoregional recurrence-free survivals in the absence of radiotherapy (2).
Although elderly patients are underrepresented in clinical trials, the relationship between age and survival in breast cancer is now well established. All large studies concur that the effect of age is biphasic: high mortality in younger women, lowest in menopausal women, and then increasing again with age (Tai P: personal communication). To provide a concrete representation of the biphasic relationship and to obtain quantitative estimates of the risks associated with age, consider a cohort of low-risk patients who have a primary breast carcinoma 2 cm or less in diameter, and a status of pN0 (axillary dissection) selected from the Surveillance, Epidemiology, and End Results (SEER) database, for diagnostic years 1988–1997 (4). Figure 1 shows counts and rates of death in this cohort as a function of age. The average follow-up was 7.8 years. Despite the short follow-up period and the overall low breast cancer–specific death rate, the biphasic shape is immediately apparent: high breast cancer death rates in patients younger than 50 years and a small but steady increase in patients aged 50 years or older (Fig. 1, D). This biphasic relationship clarifies how breast cancer can be misperceived as being indolent in older patients. Group comparisons indicate that postmenopausal patients, as a group, have a lower risk of breast cancer death than younger premenopausal patients (Fig. 1, D). But by each successive year of age within their group, the older postmenopausal patients have a greater risk of dying of breast cancer than do younger postmenopausal patients (Fig. 1, D), which shows that older age is not associated with lower risk.
|
2 cm, pN0, excluding high-grade and estrogen receptor–negative tumors, from the Surveillance, Epidemiology, and End Results (SEER) Program 2004 database (9 registries), diagnostic years 1988–1997 (Should we infer from the unremitting risk that all patients, regardless of age, should receive adjuvant radiotherapy? Kunkler et al. draw attention to the importance of competing risks of death. Figure 1, E, shows an exponential increase of non–breast cancer deaths with age. Figure 1, F, shows the corresponding odds of non–breast cancer death. At age 60 years, the odds of death from breast cancer versus other causes are 1 : 2.5. At age 65 years, the odds are still substantial: 1 : 3.5. At age 70 years, the odds are 1 : 5. At age 80 years, the odds are 1 : 10. Considering mortality only, these odds suggest that it is reasonable to propose that low-risk older patients participate in the PRIME II trial. But taking local recurrences into account, if patients are considered fit for surgery, then it is unclear why they should be denied the chance to have radiotherapy to reduce their risk of recurrence. The evidence of risk reduction is strong, and improvements that will benefit low-risk and fragile patients are within reach (5). Shouldn't the priority be to enroll these patients in trials of alternatives to conventional radiotherapy, whether it be short-course (6) or intra-operative radiotherapy (7)?
REFERENCES
1 Tinterri C, Gatzemeier W, Andreoli C, Regolo L, Zanini V, Giorgi I, et al. Breast conservative surgery with and without radiotherapy with early stage breast cancer: a prospective randomised multi-centre trial [abstract 378]. Eur J Cancer Suppl 2004;2(Suppl 3):166.
2 Kemeny M. Review of current surgical oncology trials. Advancing Cancer Care in the Elderly (ACCE), Geriatric Oncology Consortium Conference, September 18–20, 2003, Washington, DC. Available at http://www.thegoc.org/pdf/ppt/Kemeny_Margaret.pdf. [Last accessed: May 24, 2004.]
3 Hughes KS, Schnaper L, Berry D, Cirrincione C, McCormick B, Shank B, et al. Comparison of lumpectomy plus tamoxifen with and without radiotherapy (RT) in women 70 years of age or older who have clinical stage I, estrogen receptor positive (ER+) breast carcinoma [abstract 93]. Proc ASCO 2001;20:24a. Available at http://www.asco.org/ac/1,1003,_12-002643-00_18-0010-00_19-0093,00.asp. [Last accessed: July 7, 2004.]
4 Surveillance, Epidemiology, and End Results (SEER) Program. SEER 1973–2001 Public-Use Data. Surveillance Research Program, Cancer Statistics Branch, Division of Cancer Control and Population Sciences, National Cancer Institute. Released April 2004, based on the November 2003 submission. http://seer.cancer.gov/publicdata/.
5 Vallis KA, Tannock IF. Postoperative radiotherapy for breast cancer: growing evidence for an impact on survival. J Natl Cancer Inst 2004;96:88–9.
6 Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 2002;94:1143–50.
7 Vicini FA, Kestin L, Chen P, Benitez P, Goldstein NS, Martinez A. Limited-field radiation therapy in the management of early-stage breast cancer. J Natl Cancer Inst 2003;95:1205–10.
Related Correspondence
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2004 96: 1255.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||