In a Danish Breast Cancer Group phase III trial (DBCG HYPO) reported in the Journal of Clinical Oncology, Offersen et al found no difference in the rates of breast induration with moderately hypofractionated vs standard fractionated radiotherapy in women with early breast cancer or ductal carcinoma in situ (DCIS).
The trial included 1,854 eligible patients from sites in Denmark, Germany, and Norway aged > 40 years who underwent breast-conserving surgery for node-negative breast cancer or DCIS. Patients were randomly assigned between May 2009 and March 2014 to receive hypofractionated radiotherapy at 40 Gy in 15 fractions (n = 917) or standard treatment with 50 Gy in 25 fractions (n = 937).
A total of 1,608 patients had adenocarcinoma, and 246 had DCIS. The primary endpoint was noninferiority of the 40-Gy vs 50-Gy regimen in 3-year grade 2 or 3 breast induration, assuming no significant difference in locoregional recurrence.
Induration Rates and Other Outcomes
The 3-year rates of induration were 9.0% (95% confidence interval [CI] = 7.2%–11.1%) in the 40-Gy group vs 11.8% (95% CI = 9.7%-14.1%) in the 50-Gy group (risk difference = −2.7%, 95% CI = −5.6% to 0.2%, P = .07). The upper boundary of the 97.5% confidence interval for the difference in incidence was 0.2%, satisfying the criteria (< 10%) for noninferiority of 40 Gy vs 50 Gy. The hazard ratio (HR) for the 40-Gy vs 50-Gy group was 0.75 (95% CI = 0.55–1.01). At 5 years, the incidence of induration was 11% vs 13% (odds ratio = 0.80, 95% CI = 0.65–0.98, P = .029).
Risk of induration was not increased by use of systemic therapies or radiotherapy boost. Telangiectasia, dyspigmentation, poor scar appearance, and pain all occurred at low rates. The majority of patients were scored as having excellent or good cosmesis, and patient-reported satisfaction with the cosmetic outcome was high. All of these outcomes were similar or better in the 40-Gy group vs the 50-Gy group.
No significant difference in 9-year risk of locoregional recurrence was observed among all patients, with rates of 3.0% (95% CI = 1.9%–4.5%) in the 40-Gy group vs 3.3% (95% CI = 2.0%–5.0%) in the 50-Gy group (risk difference = −0.3%, 95% CI = −2.3% to 1.7%). The hazard ratio was 0.90 (95% CI = 0.51–1.59).
Among the group of patients with invasive carcinoma, a total of 33 patients (2.1%) had locoregional recurrence, including 14 patients in the 40-Gy group and 19 patients in the 50-Gy group (HR = 0.75, 95% CI = 0.37–1.49, P = .41). Among patients with DCIS, 14 patients (7.7%) had locoregional recurrence, including 8 in the 40-Gy group vs 6 in the 50-Gy group (HR = 1.40, 95% CI = 0.49–4.05, P = .53).
Overall survival at 9 years was 93.4% (95% CI = 91.0%–95.2%) in the 40-Gy group vs 93.4% (95% CI = 91.1%–95.1%) in the 50-Gy group (HR = 0.98, 95% CI = 0.65–1.47, P = .93).
The investigators concluded, “Moderately hypofractionated breast irradiation of node-negative breast cancer or DCIS did not result in more breast induration compared with standard fractionated therapy. Other normal tissue effects were minimal, with similar or less frequent rates in the 40-Gy group. The 9-year locoregional recurrence risk was low.”
Birgitte V. Offersen, MD, PhD, of the Department of Experimental Clinical Oncology, Aarhus University Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Danish Cancer Society, the Centre for Interventional Research in Radiation Oncology, and the Danish Comprehensive Cancer Center Radiotherapy Group. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.