Long-Term Results of a Randomized Trial of Tamoxifen With or Without Radiation in Women Over 50 Years of Age With T1/2 N0 Breast Cancer

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 10, 2006

Presenter: A. Fyles
Presenter's Affiliation: Princess Margaret Hospital
Type of Session: Scientific

Background

Multiple studies have attempted to define a population of women with early stage breast cancer in whom the inclusion of radiation as a part of breast conservation treatment is not necessary
This report represents long-term results of a multi-center, prospective, randomized trial evaluating the use of lumpectomy and tamoxifen, with or without external beam radiotherapy, in early stage breast cancer patients over the age of 50 years.

Materials and Methods

769 patients with pT1 or pT2, node-negative breast cancer, with microscopically negative margins following lumpectomy, were enrolled between December 1992 and June 2000
Patients >65 years of age were allowed on study based on clinical node-negativity; otherwise, patients were pathologically node-negative
Participants were stratified by T stage and estrogen status, and randomized to radiation treatment with tamoxifen 20 mg taken daily for 5 years versus tamoxifen alone

Results

The median follow-up duration was 7.8 years
The median age of the participants was 68 years
639 (83%) patients had pT1 tumors, 723 (94%) patients were ER/PR (+), 636 patients were pN0, and 132 patients were cN0
Patient and tumor characteristics were well-balanced between the 2 arms
Local relapse at 8 years was significantly lower in the tamoxifen and radiation arm versus the tamoxifen alone arm (11.5% vs. 3.8%, p<0.0001)
Disease-free survival at 8 years was significantly lower in the tamoxifen and radiation arm versus the tamoxifen alone arm (82% vs. 76%, p=0.046)
There was a trend at 8 years for decreased distant relapse in the tamoxifen alone arm versus the tamoxifen and radiation arm (3.8% vs. 5.6%, p=0.075)
There was a trend at 8 years for decreased axillary relapse in the tamoxifen and radiation arm versus the tamoxifen alone arm (1.2% vs. 2.9%, p=0.08)
There was no statistical difference at 8 years between the 2 arms with respect to overall survival, contralateral breast cancer, or second malignancy
In a planned subgroup analysis of patients with T1, receptor-positive tumors, there was a significant decrease in local relapse at 8 years in the tamoxifen and radiation arm (n=306) versus the tamoxifen alone arm (n=305) (9.2% vs. 3.8%, p=0.00098); this difference remained significant in patients ≥60 years of age (6.5% vs. 3.5%, p=0.035)
In an unplanned subgroup analysis of patients ≥60 years of age with ≤1 cm, receptor-positive tumors, there was no statistical difference at 8 years between the tamoxifen and radiation (n=125) and tamoxifen alone (n=138) arms with respect to local relapse (4.8% vs. 4.2%, p=0.73)

Author's Conclusions

All women benefited from tamoxifen and radiation at 8 years
Women ≥60 years of age with ≤1cm, receptor-positive tumors may do reasonably well with the omission of radiation from the breast conservation regimen
Updated results from the similar CALGB study will be helpful in further defining a subgroup of patients in whom radiation may be omitted from the breast conservation regimen

Clinical/Scientific Implications

The updated results of this trial provide further evidence that older women with small, receptor-positive tumors may be considered for treatment with lumpectomy and hormone therapy only. The standard of care, however, remains lumpectomy, radiation, and hormone therapy, and any omission of radiation should occur only after careful discussion between the patient and radiation oncologist.