C.C. King

Breast-Conserving Surgery With or Without Radiotherapy: Pooled-Analysis for Risks of Ipsilateral Breast Tumor Recurrence and Mortality

In a recent article in the Journal, Vinh-Hung and Verschraegen (1) provided a valuable pooled analysis of randomized trials of postoperative radiotherapy after breast-conserving surgery. They reported a small increase in breast cancer mortality and a substantial risk of local recurrence from the omission of breast radiotherapy. These important observations should not be interpreted to imply that all patients require breast radiotherapy after breast-conserving surgery and appropriate systemic therapy. We believe, however, that in contrast to younger patients, there are insufficient data to draw this conclusion in older patients. Indeed, the U.S. National Institutes of Health, in its 2000 consensus statement for breast cancer (2), makes no specific recommendation on adjuvant therapy for patients aged 70 years or older because of the paucity of data for this group of patients. Of the 15 randomized trials assessing the role of breast radiotherapy or its omission included in the pooled analysis by VinhHung (1), only three (Uppsala-Orebro, Tokyo, and the Cancer and Leukemia Group B [CALGB]) included patients over age 70. In this older group of patients, there are competing risks of mortality from predominantly vascular comorbidity. In addition, a body of data from both randomized and nonrandomized trials suggests that the risks of local recurrence decrease with age (3). This observation reflects, in part, the increasing proportion of older patients with good prognostic characteristics. Large, adequately powered trials with older patients are needed to assess the role of breast radiotherapy in local recurrence and breast cancer mortality. The dramatic impact of the competing risks of non– breast cancer mortality in the elderly is shown in the CALGB 9343 trial (4), cited in table 1 of Vinh-Hung and Verschraegen (1), which randomly assigned patients with T1, node-negative, ER-positive tumors to breast radiotherapy or no further treatment after breast-conserving therapy and tamoxifen. Of the 39 deaths among the 647 patients in the trial, only one was due to breast cancer. Ongoing trials, such as the Postoperative Radiotherapy In Minimumrisk Elderly (PRIME) trial (5), are addressing issues of local control, morbidity, and quality of life in older, low-risk patients to establish a firm basis for the selection of patients for radiotherapy in this age group. We feel that until the results of randomized trials focused on evaluating breast radiotherapy in the elderly are available, the role of breast radiotherapy in this age group remains uncertain. For many such women, their informed recruitment into appropriately designed, randomized, controlled trials may be the most ethical way of determining treatment.

Breast radiotherapy: considerations in older patients.

With an ageing population, the number of older women with breast cancer eligible for adjuvant irradiation after breast conserving surgery and mastectomy is rising. There is a dearth of level 1 data on the effect of adjuvant irradiation on local control, quality of life and survival. In large part this reflects the exclusion of patients over the age of 70 years from randomised trials. The prevention of local recurrence may reduce the risks of dissemination. However, older women with early breast cancer and a life expectancy of less than 5 years are unlikely to derive a survival benefit from adjuvant radiotherapy. Rates of access of older patients to adjuvant irradiation are lower than for younger patients. Physician and patient bias and co-morbidities are contributory factors. There are also competing risks of mortality from co-morbidities, particularly in women over the age of 80 years. Postoperative radiotherapy after breast conserving surgery does not seem to compromise overall quality of life of older patients. Although the absolute reduction in local recurrence from adjuvant radiotherapy is modest in lower risk older patients after breast conserving surgery and adjuvant systemic therapy, there has to date been no group of fitter old patients defined from whom radiotherapy can be reasonably omitted. Guidelines for postmastectomy radiotherapy should not differ from younger patients. Adequately powered randomised trials are needed to assess the effect of adjuvant irradiation in older patients on outcomes after breast conserving surgery and mastectomy to provide a more robust basis for evidence-based radiotherapy practice.

The PRIME (Post-Operative Radiotherapy in Minimum-Risk Elderly) Breast Cancer Trial of Adjuvant Radiotherapy after Breast Conserving Surgery: Impact on Quality of Life and Cost-Effectiveness at Three Years.

Background:Breast cancer in older women is a major and rising health care burden, due to demographic changes in the population. This places increasing pressure on the finite resources of radiotherapy treatment centres.If local recurrence rates in older ‘low risk’ patients were sufficiently low with the omission of radiotherapy (RT) following breast conserving surgery and adjuvant endocrine therapy, decisions on treatment might be influenced by considerations of Quality of Life (QoL) and cost-effectiveness.Methods: Patients over the age of 65 with a ‘low risk’ breast cancer (T0-2,N0,M0) were randomised to receive whole breast RT (40-50 Gy in 15-25 fractions) or no further treatment. All patients received endocrine therapy.Participants completed a questionnaire at baseline (before randomisation), two weeks after the end of RT (or equivalent time), and then at nine, 15 and 36 months after surgery. QoL was measured by the EORTC QLQ-C30 and -BR23 modules. The Hospital Anxiety and Depression Scale was included to measure mental health, and the EuroQol was used to calculate QALYs for the assessment of cost-effectiveness. Some open-ended questions were included to capture items of potential importance to the patients.Results: Although no differences in the overall QoL scores were detected, there were statistically significant differences between the irradiated and non-irradiated groups in insomnia (higher in the no RT group, p=0.01), breast symptoms (higher in the RT group, p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 958.