Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial

Background and purpose: Unlike squamous carcinomas, breast adenocarcinoma may be as sensitive to fraction size as late dose-limiting normal tissues. If so, fewer larger fractions would be as safe and effective as regimens based on 2.0 Gy fractions. The first step is to test the effects of radiotherapy fractions > 2.0 Gy on late normal tissue responses in the breast after tumour excision and radiotherapy for early breast cancer. Patients and methods: One thousand four-hundred and ten women with T1-3 N0-1 M0 invasive breast cancer were randomised between 1986-98 into one of three radiotherapy regimens after local tumour excision of early stage breast cancer; 50 Gy in 25 fractions (F) vs two dose levels of a test schedule giving 39 or 42.9 Gy in 13 F over 5 weeks. Fraction sizes were 2.0, 3.0 and 3.3 Gy, respectively. The primary endpoint was late change in breast appearance compared to post-surgical appearance scored from annual photographs blinded to treatment allocation. Secondary endpoints included palpable breast induration (fibrosis) and ipsilateral tumour recurrence. Results: After a minimum 5-year follow up, the risk of scoring any change in breast appearance after 50 Gy/25 F, 39 Gy/13 F and 42.9 Gy/13 F was 39.6, 30.3 and 45.7%, from which an alpha/beta value of 3.6 Gy (95% CI 1.8-5.4) is estimated. The alpha/beta value for palpable breast induration was 3.1 Gy (95% CI 1.8-4.4). Conclusions: An alpha/beta value of around 3 Gy for late normal tissue changes in the breast is derived from the estimated equivalence of 41.6 Gy in 13 fractions and 50 Gy in 25 fractions over 5 weeks, in line with trial predictions. (c) 2005 Elsevier Ireland Ltd. All rights reserved.