Abstract
Introduction: Because more women are surviving breast cancer, the focus has shifted to analyzing the long-term treatment-related toxicity. Cardiovascular diseases are major long-term side effects of radiotherapy, but knowledge is limited regarding long-term risks because published studies have, on average, < 20 years of follow-up. In the present investigation, we report on all-cause and cardiovascular mortality during the long-term follow-up of 7 711 French female breast cancer patients, treated between 1954 and 1984 and followed up for 28 years on average.
Methods: All-cause mortality in the cohort was compared with the French general population using Standardized Mortality Ratios (SMRs) and the Absolute Excess Risk (AER) estimated by Poisson regression. Mortality from cardiovascular diseases was analyzed among women who survived at least 5 years after treatment. Proportional hazard regression was used for the statistical analysis. Multivariate analysis was performed to evaluate the effect of radiotherapy on cardiovascular long-term mortality.
Results: During the 1954-2004 follow-up period, 5 436 women died among which 421 from cardiovascular diseases. All-cause mortality was 3.15-fold higher in the cohort than in the general French female population. Mortality in the cohort decreased from 6.86 to 1.26 during the first 30 years of follow-up, and then increased again to 1.60. Risk of death was more than 2-fold higher in women who had received radiotherapy during initial treatment than in those who had not, and this difference was higher for women treated before 1976 than afterwards (p < 0.0001). Risk of death was also higher for women who had stage II, III or IV disease than for those with less advanced tumors. When analyzed separately risks of death from cardiac and vascular diseases were 1.76 (95% Confidence Interval (CI): 1.34-2.31) and 1.33 (95% CI: 0.99-1.80) in women who received radiotherapy, compared with women who had not received radiotherapy. Among women who received radiotherapy, those who had been treated for a left-sided breast cancer had a 1.56-fold (95% CI: 1.27-1.90) higher risk of cardiac mortality than those treated for a right-sided breast cancer, and this risk increased with time since breast cancer diagnosis (p<0.05).
Conclusions: Excess deaths observed during the first two decades following breast cancer diagnosis were significantly associated with initial clinical characteristics of the tumor and to radiotherapy. Radiotherapy, as delivered until the mid-1980s increased the long-term risk of death from cardiovascular diseases, in particular among women treated for a left-sided breast cancer, with contemporary tangential breast or chest wall radiotherapy. This risk may increase with a longer follow-up, even after 20 years following radiotherapy.
Key words: Breast cancer, Radiotherapy, Long-term mortality, cardiovascular mortality
Biography:
Dr Houda Boukheris received her M.D. from the University of Constantine, in Algeria. After 4 years of medicine practice she enrolled in a residency program to complete a postgraduate degree in epidemiology and preventive medicine in the University of Algiers. From 2001 to 2004, she served as a medical epidemiologist in charge of the local implementation, coordination, and evaluation of national programs to control and prevent transmissible diseases, maternal and infant mortality, and led studies to determine incidence patterns of nosocomial infections in University Hospital settings. In 2004, Dr Boukheris was awarded a fellowship from the International Agency for Research on Cancer (IARC) and joined the French National Institutes of Health and Medical Research in Paris, France, where she coordinated studies to assess the long term mortality and risk of cardiac diseases among French women treated with radiotherapy for breast cancer. In 2007 she was awarded a postdoctoral fellowship from the U.S. National Cancer Institute, National Institutes of Health (NCI/NIH), and joined the Radiation Epidemiology Branch in the Division of Cancer Epidemiology and Genetics (REB/DCEG) where she continued collaboration in research projects to assess the long-term risk of second cancers after a primary cancer in childhood and adulthood using North American and U.S. population-based data of cancer survivors. During her time at NCI/NIH Dr Boukheris was also involved in the preparation of the international meeting held by the NCI in 2008 aimed at proposing an international collaboration for thyroid carcinoma genetic susceptibility, and the implementation of a pooled case-control study on risk factors of inflammatory breast cancer in North Africa. In 2010, she joined Nova Resarch Company in Bethesda, MD as a Research Scientist where she continued collaboration on projects aimed at analyzing the U.S. NCI/NIH funded research portfolio and led literature review and report writing on breast cancer research to identify research gaps and emerging areas in breast cancer control and prevention research. Dr Boukheris serves currently as an Assistant Professor of Epidemiology in Algeria, where she is leading the first population-based investigation on thyroid cancer incidence and patterns, using Age-Period-Cohort models. Her research interests also include cancer registries validation using quantitative and semi-quantitative methods as recommended by the European Network of cancer registries and the International Association of Cancer Registries.
