Cardiac late effects after modern 3D-conformal radiotherapy in breast cancer patients: a retrospective cohort study in Germany (ESCaRa)

Abstract

Purpose Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany. Methods A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account. Results After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85–1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88–1.25). Conclusions Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy.

Accelerated hypofractionated breast radiotherapy with simultaneous integrated boost: a feasibility study

“…However, all these doses were estimated retrospectively. In a recent study Merzenich et al [28] reported that average MHD of 4.6 Gy for left-sided breast RT and only pre-exiting cardiac disease was associated with risk of cardiac death. While another study reported V 25 and V 30 to be detrimental to the heart [29].…”

Cancer survivor late-effects, chronic health problems after cancer treatment: what’s the evidence from population and registry data and where are the gaps?

“…Two or more CVRFs at cancer diagnosis led to greater cardiovascular disease (CVD) after cancer treatment and this then impacted on patients’ overall survival (Table 1) [13,15]. Those populations at higher risk of CVRF were women treated for breast cancer, people treated for multiple myeloma, lung cancer or non-Hodgkin lymphoma (NHL) and those women who were older [13,14▪▪,16].…”

“…Those on trastuzumab had a higher 5-year cumulative incidence than women on chemotherapy alone (5.2% vs 2.5%, P < 0.001) Trastuzumab increased risk of HF Koric et al 2022 [14]USA Population based retrospective cohort study of 6641 women with breast cancer , treated between 1997 and 2009. Study to evaluate CVD and possible risk factors Age matched comparison of people without cancer Women identified from the Utah cancer registry database who had survived 10 years Breast cancer survivors had an increased risk of newly diagnosed diseases of the circulatory system (HR = 1.32; 99% CI 1–1.75) 10–15 years following cancer diagnosis compared with the matched population Women with more comorbidities had a higher risk of CVD beyond 10 years (HR = 2.64; 95% CI 1.08–6.45).Older age, obesity, lower education and family history of CVD were risk factors for CVD Merzenich et al 2022 [16]Germany Retrospective cohort of 11 982 women treated with radiotherapy for breast cancer between 1998 and 2008. Study to explore cardiac toxicity through mortality data and patient self-reported comorbidity data ( n = 5388) Within group comparator of women treated for left- or right-sided radiotherapy fields Median follow-up of 11.1 years There was no significant association of morbidity and mortality from cardiac events and laterality of radiation therapy.…”

The risk of cardiovascular toxicity caused by cancer radiotherapy—a narrative review

“…As described above, accumulated studies and clinical evidence indicated that cardiac mortality and morbidity of breast cancer survivors treated with conventional RT was increased, and thus, for chronic cardiac events in breast cancer patients treated until the 1990s, RT was referred as a risk factor (34). However, improved modern techniques minimize heart doses and reduce radiation exposure of the heart.…”

“…However, improved modern techniques minimize heart doses and reduce radiation exposure of the heart. Merzenich and colleagues investigated cardiac mortality and morbidity of breast cancer survivors treated with contemporary RT in Germany (34). A total of 11,982 breast cancer patients treated between 1998 and 2008 were included in the retrospective cohort study.…”