Can Older Early-Stage Breast Cancer Patients Skip Radiation?

Kate Johnson

May 22, 2013

There is no benefit in adding radiation to tamoxifen therapy in women aged 70 years or older after lumpectomy for early-stage breast cancer, according to extended, long-term results of the Cancer and Leukemia Group B (CALGB) 9343 trial.

"Irradiation adds no significant benefit in terms of survival, time to distant metastasis, or ultimate breast preservation," noted author Kevin Hughes, MD, from Harvard Medical School, and colleagues in an article published online ahead of print in the Journal of Clinical Oncology.

Median follow-up for the trial is now 12.6 years, and the 10-year results back up the trial's previous 5-year data.

As previously reported by Medscape Medical News, those results prompted the National Comprehensive Cancer Network (NCCN) to adjust its treatment guidelines, so that it no longer recommends radiation therapy after lumpectomy in older women with estrogen receptor (ER)–positive early breast cancer who are receiving endocrine therapy.

However, despite this, the authors note that their initial findings had "little impact" on clinical practice, "with the use of irradiation only slightly diminishing in this population."

There was concern that with longer follow-up, the number of recurrences would increase, they noted, adding that the durability of the longer-term results is "encouraging."

However, an accompanying editorial shows there is still some resistance to the idea of withholding radiation entirely in this population.

"We support this conclusion for patients age 75 or older with low- to intermediate-grade disease and for those with shorter life expectancies as a result of comorbidities," wrote Benjamin Smith, MD, and Thomas Buchhotz, MD, from the University of Texas MD Anderson Cancer Center, in Houston. "However, we feel that radiation use continues to be appropriate for patients younger than age 75 and those with high-grade tumors."

And in a Grand Rounds commentary that appears in the same issue of the journal, Jaroslaw Hepel, MD, and David Wazer, MD, from Alpert Medical School of Brown University in Providence, Rhode Island, write, "These results provide compelling confirmation of high-quality level I evidence that for this select patient population, the administration of tamoxifen and the omission of radiation therapy is a safe and reasonable treatment approach."

However, they continue, "it is impossible to definitively declare that there are no subpopulations within the cohort of older patients...who may be at substantial risk of local failure with tamoxifen alone and may show a clinically meaningful benefit with the addition of radiation therapy."

Long-term Results

In the CALGB 9343 trial, investigators randomly assigned 636 women aged 70 years or older who were postlumpectomy for clinical stage I (T1N0M0) ER-positive breast cancer to receive either tamoxifen alone (20 mg per day for 5 years) or tamoxifen plus radiation therapy.

After a median follow-up of 12.6 years, there was a statistically significant benefit to tamoxifen and radiotherapy (TamRT, n = 317)) compared with tamoxifen alone (Tam, n = 319), with an 8% lower rate of locoregional recurrence (2% vs 10%, P < .001) and a 7% lower rate of ipsilateral breast recurrence (2% vs 9%).

However, this benefit did not translate into significant differences in terms of overall survival, distant disease-free survival, or ultimate breast preservation, the authors noted, "with the proviso that the study lacked the power to definitively show noninferiority in either arm."

Ten-year estimates of overall survival were 67% in the TamRT arm and 66% in the Tam arm (P = .64). The 10-year probability of freedom from distant metastasis was 95% in both groups.

Additionally, the 10-year probability of mastectomy-free survival was 98% and 96%, respectively (P = .17).

"Importantly, the study also shows that the impact of breast cancer in this select group of older women is much smaller than that of comorbid conditions," the authors wrote. "Of the 636 women in the study, only 21 (3%) have died as a result of breast cancer, whereas 313 (49%) have died as a result of other causes."

Contrasting Findings

In their editorial, Dr. Smith and Dr. Buchhotz outline their contrasting findings, as reported by Medscape Medical News, which point to a mastectomy-lowering benefit of radiation therapy in a similar population of older women.

"We found limited benefits for radiation use in older patients with low- to intermediate-grade disease but a highly significant absolute 10-year reduction in risk of subsequent mastectomy for patients with high-grade tumors or patients between ages 70 and 74," they wrote.

In their study, adjusted analyses showed that radiation therapy was associated with a lower risk for mastectomy (hazard ratio, 0.33; P < .001) but provided no benefit for patients aged 75 to 79 years without high-grade tumors.

Both the editorial and the commentary point out that CALGB 9343 is limited in its generalizability to all older women with T1N0 ER-positive breast cancer because important risk factors for locoregional recurrence, such as tumor grade and lymphovascular space invasion, were not evaluated.

Comorbidity and life expectancy are also important factors when weighing the toxicity considerations of radiotherapy, the commentators note.

For their part, the study authors emphasize that their goal with this research was to identify patients who would not benefit from radiotherapy in order to "offer this cohort of women another treatment option that might decrease morbidity, allow for adaption to social issues, and not complicate other medical problems."

Although CALGB 9343 identifies an age and stage for which the foregoing of radiotherapy may be considered, the debate continues regarding distinct subgroups.

Dr. Smith disclosed research funding from Varian Medical Systems. All other authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online May 20, 2013. Abstract, Editorial, Commentary


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