Clinicians might want to offer radiation therapy to some older women (70 to 79 years of age) with early breast cancer because it lowers the risk for recurrence and subsequent mastectomy, according to a new American observational study.
The study of women in a "real-world" setting shows a benefit for radiation therapy after lumpectomy in this older patient population. This finding is in contrast to findings from a previous clinical trial, which prompted clinical guidelines to no longer recommend radiation therapy in this group.
The study, published online August 13 in Cancer, showed that at 10 years, radiation therapy was associated with a lower absolute risk for mastectomy in the same breast, compared with no radiation therapy (3.2% vs 6.3%).
This translates into a statistically significant relative reduction of two thirds in the risk for subsequent mastectomy (hazard ratio, 0.33; P < .001).
Most of the women (87.6%) in the 7403-patient cohort, derived from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database, were treated with radiation therapy. A small percentage of the total population had a recurrence; only 174 patients (2.4%) underwent mastectomy in the same breast after initial surgery during the study period (1992 to 2002), which had a median follow-up of 7.2 years.
These findings led the study authors to conclude that radiation therapy is "associated with a greater likelihood of ultimate breast preservation for most older women with early breast cancer."
The study did not assess overall survival. Instead, it was designed to determine whether adjuvant radiation therapy reduced the risk for mastectomy in women with stage I estrogen-receptor (ER)-positive breast cancer.
In effect, the study is an analysis of radiation therapy in routine practice. The use of radiation therapy in older women with early breast cancer was also studied in the major clinical Cancer and Leukemia Group (CALGB) 9343 trial.
In that randomized trial, radiation therapy resulted in a statistically nonsignificant 50% relative reduction in the risk for subsequent mastectomy. The absolute risk at 10 years was 4% for those who did not receive radiation therapy, compared with 2% for patients who did receive radiation therapy. There was no significant difference in survival between the 2 groups.
On the basis of the CALGB findings, the influential National Comprehensive Cancer Network (NCCN) adjusted its treatment guidelines, and now no longer recommends radiation therapy after lumpectomy in older women with ER-positive early breast cancer who are receiving endocrine therapy.
However, Benjamin Smith, MD, from the University of Texas M.D. Anderson Cancer Center in Houston, lead author of the current study, stopped short of saying the NCCN guidelines need to be reversed.
"I think the national guidelines, while well intended and important, may gloss over the certain nuances needed for making critical decisions with patients," he said in a press statement. "Our study may shed additional light on some of those nuances, and provides data that physicians can use when talking to their patients about whether to go forward with radiation."
Dr. Smith and his coauthors also acknowledge that randomized trials such as CALGB 9343 are "the gold standard of clinical evidence." But they point out that such trials "often do not have sufficient power to permit meaningful subgroup analyses, making it difficult to determine which subgroups of patients are more or less likely to benefit from the therapy under consideration."
The study authors suspect that there are differences between a "motivated clinical trial population" and the "general population" of women with ER-positive early breast cancer. For example, poor compliance with endocrine therapy is "common" in the general population, the authors report. Thus, they hypothesized (correctly) that radiation therapy would be even more beneficial in routine practice than it was in the CALGB trial.
Selecting Patients
The findings from the current study, with its subset analyses of clinicopathologic features, can help clinicians identify which patients are more or less likely to benefit from radiation therapy, suggest the authors.
For instance, in subset analyses, the study authors found that radiation therapy provided no benefit for patients 75 to 79 years of age without high-grade tumors who had a pathologic lymph node assessment (P = .80); however, for all other subgroups, radiation therapy was associated with an absolute reduction in risk for mastectomy that ranged from 4.3% to 9.8% at 10 years.
Which patient groups are more likely to benefit?
The study authors highlighted several groups, including patients with high-grade early breast cancers, who had a 6.7% absolute reduction in the 10-year risk for mastectomy; patients who undergo the less sophisticated clinical lymph node assessment (4.9% absolute reduction); and any patient 70 to 74 years of age (3.8% absolute reduction). These types of patients had some of the most pronounced benefits from radiation therapy, followed by most patients with other clinicopathologic features.
This study is not the only recent effort on radiation therapy in older women with early breast cancer by the study authors.
They recently published a paper on a nomogram that converts clinical data into estimates of mastectomy-free survival, as reported by Medscape Medical News (J Clin Oncol. 2012;30: 2837-2843). The tool aims to help clinicians refine their advice about radiation therapy to older women with early breast cancer.
In an editorial that accompanied the nomogram paper (J Clin Oncol. 2012;30:2809-2811), an expert suggested that nomograms might be a step forward in the ongoing effort to refine decision making about radiation therapy in this setting.
However, the nomogram needs validation, said David Wazer, MD, from the Tufts University School of Medicine in Boston, Massachusetts, and the Alpert Medical School of Brown University in Providence, Rhode Island.
In the meantime, Dr. Wazer advised clinicians to check out the modeling tool on the IBTR! Web site, which predicts 10-year risk for in-breast recurrence both with and without radiation therapy. The modeling tool, which uses clinical trial (randomized and not) data but not observational study data, is the "most reliable" of the available risk-assessment tools, he said.
A portion of this study was funded by a research grant from Varian Medical Systems. The study was also supported by the Department of Health and Human Services and the National Cancer Institute. The authors have disclosed no relevant financial relationships. Dr. Wazer reports being a consultant to Advanced Radiation Therapy.
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