Measuring the Value of Radiotherapy in Older Women With Breast Cancer
Authors: David E. Wazer
Journal: Journal of Clinical Oncology (2012)

Breast-conserving therapy (BCT) represents a major advance in the treatment of breast cancer. Multiple randomized trials have found comparable outcomes between BCT and mastectomy, allowing women to preserve their breast without compromising the ability to be cured of cancer. Beyond the simple preservation of the breast, BCT has been associated with improved quality of life, including social functioning, body image, and physical functioning, compared with mastectomy. Radiation therapy represents an integral part of BCT; multiple trials have consistently shown increased rates of ipsilateral breast tumor recurrence (IBTR) in women undergoing breastconserving surgery when radiation therapy is omitted, even among women considered at low risk for IBTR. In addition to the reduction of local tumor recurrence, radiotherapy after breast-conserving surgery reduces the risk of breast cancer death by one sixth, as demonstrated in the recent update of the Early Breast Cancer Trialists’ Group meta-analysis. However, the benefit of radiotherapy is clearly dependent on the baseline risk of IBTR after surgical excision alone and, in absolute terms, is small in patients at low risk. Multiple clinical trials have shown that the risk of IBTR decreases with age, and that in turn has prompted analysis of the value of radiotherapy for older patients with breast cancer. The CALGB (Cancer and Leukemia Group B) 9343 trial demonstrated that radiotherapy has no discernable benefit as measured by either mastectomy-free (MFS) or overall survival in a highly selected group of patients age 70 years or older with estrogen receptor (ER) –positive tumors who received 5 years of tamoxifen. On the basis of these findings, the treatment guidelines of the National Comprehensive Cancer Network were amended to state that radiotherapy may be reasonably omitted in women age 70 years or older with ER-positive stage I breast cancer who receive antiestrogen endocrine therapy. Despite the availability of level I evidence supporting the omission of radiotherapy in patients age 70 years or older who receive hormonal therapy, a recent Surveillance, Epidemiology, and End Results (SEER) –Medicare database analysis by Soulos et al showed minimal impact of these clinical trial data in decreasing the use of radiotherapy after breast conservation in low-risk older women. This suggests that oncologists perceive meaningful differences as being present between patients treated in routine clinical practice compared with those enrolled onto clinical trials. This is likely the result of multiple factors, including concerns related to well-documented shortcomings in patient compliance with long-term therapy with either tamoxifen or an aromatase inhibitor. As such, the impact of removing breast radiotherapy from the treatment regimen in the general population of older patients is not known. Furthermore, few data exist as to whether radiotherapy can be reasonably omitted in older patients who have more advanced tumors, are ER negative or node positive, and are presumed to be at somewhat higher risk of IBTR. In the article that accompanies this editorial, Albert et al attempt to address these issues by performing an analysis of the SEERMedicare data set. The authors identified a cohort of more than 16,000 patients age 66 to 79 years and assessed clinical and pathologic factors associated with failure to preserve the breast after initial breast cancer treatment. The factors derived from this analysis were then used to generate a nomogram to provide an individualized assessment of subsequent mastectomy risk (with and without radiotherapy) and to quantitatively estimate the value of radiotherapy for risk reduction. In their study, Albert et al observed a 10-year MFS of 95%. Factors found on multivariate analysis to be predictive of time to mastectomy after definitive initial local therapy included age, race, tumor size, ER status, and receipt of radiotherapy. Because nodal status showed a significant interaction with the receipt of radiotherapy, it was included with the other variables in the construction of the nomogram. The authors used a self-validation technique that found a bootstrap-corrected concordance index comparable to some other previously described breast cancer decision analysis tools. Recent years have seen the introduction of several predictive algorithms to assist with adjuvant therapy decision making in breast cancer treatment. The most prominent among these is Adjuvant!, which was developed to give individualized estimates of breast cancer mortality risk and quantify the relative benefit of systemic therapy options. Ravdin et al initially constructed Adjuvant! in 2001 by using the SEER-Medicare data set to provide baseline risks of overall recurrence and mortality and then applied the results of systemic therapy meta-analyses to quantitatively estimate the effects of adjuvant chemotherapy or hormonal therapy. Despite the clear desirability for a similar tool to assist clinicians and patients in evaluating the relative utility of breast radiotherapy, the application of a methodology parallel to that used in the construction of Adjuvant! is impossible, because the SEER-Medicare data set does not contain information specifically related to local recurrence. Furthermore, critical variables that influence the risk of IBTR, such as the JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 23 AUGUST 1