Radiation Therapy for Patients with Invasive Breast Cancer: 3 Weeks Proves as Effective as 5 Weeks

Get Permission

Patients [with invasive breast cancer] can be safely treated to a lower dose with fewer fractions than the historical standard.

—John Yarnold, MD

Ten-year follow-up of the two-part UK Standardisation of Breast Radiotherapy Trials (START) supported the 5-year findings, demonstrating that a 3-week course of adjuvant radiation therapy is equivalent to a 5-week course of radiation for women with invasive breast cancer. The update was presented at the 2012 San Antonio Breast Cancer Symposium.1

Five-year results of START A, presented in 2008, showed that breast cancer is as sensitive to fraction size as late-reacting normal tissues, so there is no advantage to 2-Gy fractions. Five-year results of START B showed that patients can be safely and effectively treated at a total lower dose of radiation with fewer fractions than the historical standard of 50 Gy delivered over 5 weeks.

“No detrimental effects of hypofractionation were identified in the trial or in any subgroup. These results support the current [National Institute for Health and Clinical Excellence] (NICE) guidelines for 40 Gy in 15 fractions as the UK standard of care for all patients with invasive breast cancer,” stated lead author John Yarnold, MD, on behalf of the START trialists. Dr. Yarnold is Professor of Clinical Oncology at The Institute of Cancer Research in London.

Study Specifics

START A enrolled 2,236 women with complete surgical excision of stage I to III invasive breast cancer with one involved lymph node and no known metastasis. Patients were randomly assigned to 50 Gy delivered in 25 fractions over 5 weeks (control group) vs 39 Gy or 41.66 Gy delivered in 13 fractions over 5 weeks.

“This study allowed interpolation to enable a direct estimate of fraction sensitivity,” Dr. Yarnold explained.

START B had a pragmatic design, and enrolling 2,215 patients with the same criteria from 35 centers in the United Kingdom. Patients were randomly assigned to receive the same control arm treatment vs 40 Gy in 15 fractions over 3 weeks.

Baseline characteristics in both trials were comparable in the treatment arms. Mean age was 57 years, 25% had node-positive disease, 33% received adjuvant chemotherapy, and 75% were on adjuvant tamoxifen. Patients enrolled in START B had slightly more favorable prognostic features, Dr. Yarnold said.

START A showed no evidence that the control arm was better than the other two arms in terms of adverse events, and there was clear evidence that 39 Gy was associated with fewer side effects, he continued. No significant differences were observed between 50 Gy and 41.6 Gy in tumor control; local recurrence rates were comparable.

“39 Gy was slightly more gentle on the cancer,” Dr. Yarnold commented.

Adverse Events

START B showed a clear reduction in adverse events with 40 Gy delivered in 15 fractions vs 50 Gy in 25 fractions. The risk of adverse events was reduced by 23% using the shorter schedule, with an absolute 8% reduction in adverse events. According to physician assessment, rates of adverse events were lower in the 40-Gy arm, including breast shrinkage, induration, and edema.

No difference in recurrence was observed between the two arms.

“It is unlikely for the shorter schedule to be more than 1% inferior, and it could be 2.5% better in tumor control,” Dr. Yarnold told listeners.

Further Analysis

Subgroup analysis of both START A and START B showed no difference in outcomes by age, primary surgery type, presence or absence of axillary nodes, tumor grade, use of boost radiation, and adjuvant therapy.

“We conclude that there is no advantage to the continued use of 2-Gy fractions [as in 50 Gy delivered in 25 fractions]. Patients can be safely treated to a lower dose with fewer fractions than the historical standard,” Dr. Yarnold stated.

During the discussion following the presentation, Dr. Yarnold said, “I see no reason why 40 Gy delivered in 15 fractions should not be adopted as the standard in other countries.”

U.S. Perspective

“This study proves again that short-course radiation is as good as a longer course. The main advantages of a short course is that it is more convenient for patients and it costs much less than the previous standard,” stated Alphonse Taghian, MD, PhD, Professor of Radiation Oncology at Harvard Medical School and Chief of the Breast Radiation Oncology Service at Massachusetts General Hospital in Boston.

Twenty-five percent of the women who participated in the SMART trial were node-positive, and the UK standard applies to all women who require adjuvant radiation. In general, in the United States, the 3-week course is given to node-negative patients and is being used at some centers.

“Some radiation oncologists in the United States are concerned about giving a 3-week course without a radiation boost. At Massachusetts General, we follow the Canadian fractionation schedule, treating the whole breast for 3 weeks and 1 day, and adding a boost over 4 days, to complete treatment in 4 weeks instead of our standard 6 weeks,” Dr. Taghian said.

The Radiation Therapy Oncology Group (RTOG) is currently running a clinical trial comparing 6 weeks of standard radiation vs 3 weeks of radiation including a boost. That trial has enrolled higher-risk, node-negative patients with stage 0 to II breast cancer.

“If results of this study show that the short course with the boost is as effective as the 5- or 6-week course, that will satisfy radiation oncologists who feel the boost is needed. If the study is positive, the short course will become a standard option for patients who fulfill the eligibility criteria,” he said. ■

Disclosure: Drs. Yarnold and Taghian reported no potential conflicts of interest.


1. Haviland JS, Agrawal RK, Aird E, et al: The UK START (Standardisation of Breast Radiotherapy) Trials: 10-year follow-up results. 2012 San Antonio Breast Cancer Symposium. Abstract S4-1. Presented December 6, 2012.