Although radiation therapy following lumpectomy for lymph node-negative breast cancer significantly reduces both local and distant disease recurrence, overall mortality is not substantially better in women who receive radiation than in those who do not, according to a Canadian study update report in the November 20th Journal of the National Cancer Institute.
Researchers Roy M. Clark, md, Mark Levine, md, and other members of the Ontario Clinical Oncology Group add that no subgroup of patients was found to have a low enough risk of local disease recurrence to suggest that other women with similar disease characteristics might safely forego post-lumpectomy radiation therapy.
The authors note that breast-conservation surgery is now commonly used in the management of early-stage breast cancer, and clinical trials have demonstrated that breast irradiation after surgery substantially reduces the risk of cancer recurrence in the breast. In this study, 837 women in Ontario diagnosed, from April 1984 Through Februrary 1989, with breast cancer that had not spread to axillary lymph nodes were treated with lumpectomy and were then randomly assigned to receive radiation therapy to the affected breast or no further treatment. None of the women in the study received postsurgical systemic therapy.
Initial results of the study were published in 1992 after a median follow-up time of 43 months. At that time, recurrence of cancer in the breast occurred in 5.5% of patients who received breast irradiation compared with 25.7% of those who did not. No difference in survival was detected between the two groups. In addition, a low-risk patient subgroup (ie, less than a 10% chance of local disease recurrence without radiation therapy) for whom irradiation might not be necessary could not be identified.
The current report updates findings now that the median patient follow-up has reached 7.6 years. Eleven percent of the irradiated patients have experienced a recurrence of cancer in the breast, as compared with 35% of women not receiving radiotherapy. Women not receiving radiotherapy had a fourfold greater risk of local recurrence relative to those receiving the treatment. This difference was highly statistically significant. Radiation therapy also resulted in a statistically significant decrease in relapse at sites distant from the primary tumor. As in the initial data analysis, younger age (less than 50 years), tumor size (greater than 2 cm), and poor nuclear grade were found to be important predictors for local breast relapse.
Also as before, however, there was no statistically significant difference in overall survival between the two patient groups, and tumor size and tumor grade remained key predictors for mortality. Similarly, no low-risk subgroup could be identified who might not require radiation therapy.
The authors acknowledge that the failure of radiation therapy to improve overall survival while reducing local and distant relapse--demonstrated in this and other studies--remains difficult to explain. Possible explanations, they suggest, may involve the limited power of individual studies to date to detect a statistically significant survival difference, the possibility that radiotherapy reduces breast cancer mortality but increases mortality due to other causes (eg, ischemic heart disease), or that the high metastatic potential of breast cancer prevents any real benefit from radiotherapy on survival. Finally, Clark and coworkers note that, even if a low-risk group could be identified, radiation therapy is still likely to be effective. Individual decision-making, they say, will relate to the perceived value of potential benefits (eg, disease-free survival) balanced against possible adverse effects (eg, long-term radiotherapy-related morbidity) . Tumor size and nuclear grade, they add, should continue to be used as prognostic markers to guide the use of adjuvant systemic therapy.