Abstract P4-11-01: Cardiovascular Effects of Postmastectomy Irradiation Evident after 15 Years. Results from the South Sweden Breast Cancer Group's Randomised Studies SBII:1 with 25 Years of Follow-Up of Pre-and Postmenopausal Women with Stage II Breast Cancer
Authors: Malmström P , Killander F , Kjellén E , Anderson H. 
Published: April 2011

Abstract
Background: The importance of radiotherapy for local control after mastectomy and breast conservation surgery is well established with a reduction in loco-regional recurrences by two thirds. In early radiotherapy trials the reduction of loco-regional failures did not result in a reduction of mortality due to increased late non-breast cancer mortality. The 2005 overview of radiotherapy by EBCTCG did however show a significantly improved survival with the addition of radiotherapy. Patients and methods: From 1978 to 1985 1100 patients with breast cancer stage II were included in two randomized trials of radiotherapy and adjuvant systemic treatment, SBII:1 pre (Cyclophosphamide per os one year) and SB II:1 post (Tamoxifen 10 mg x 3 one year). The radiotherapy technique and the outcome of these studies have been published previously (Arwidi Å et al. Acta Radiol Oncol 18:273, 1979, Killander F et al. Eur J Cancer 43:2100, 2007, Killander F et al. The Breast 18:309, 2009). An efficient reduction of loco-regional recurrences but no improvement in survival was reported at 25 years of follow-up. Linkage to the following population based Swedish registries was obtained: 1. National Population Registry 2. National Cause of Death Registry, and 3. Swedish Hospital Discharge Registry. Per protocol treatment was administered to 1044 patients, which form the basis for the analyses. We have included both underlying and contributing causes of death due to heart, cerebrovascular and lung disease.
Results: After 15 years a significantly increased cardiac mortality was observed in irradiated patients compared to patients given systemic treatment only, and this effect prevailed at 25 years of follow-up. However not until 15 years after radiotherapy significantly higher cardiovascular mortality was observed. When analysing cerebro-vascular mortality the same pattern was seen.
Cumulative incidence of non-breast cancer mortality after postmastectomy radiation in pre-and
For lung diseases no increase in mortality was discernible. An interesting observation was that in premenopausal patients cardiovascular and cerebrovascular mortality were less pronounced, and that the latency period was longer than for postmenopausal patients.
Analyses of all hospital admissions during follow-up showed neither increased overall morbidity nor increased cardiovascular morbidity. Discussion: The significant cardiovascular side effects of radiation observed with the radiotherapy technique used in these studies underlines the importance of careful dose planning and reduction in the volumes of the heart and large vessels, that are exposed to radiation. Extended follow-up is necessary for detection of these late effects. The longer latency and lower cardiovascular mortality in premenopausal patients may reflect lower sensitivity for radiation of normal tissue compared to postmenopausal women.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-01.