late cardiac morbidity/mortality in those receiving breast conservation treatment

[Lani]

left vs. right:
ABSTRACT: Late Cardiac Mortality and Morbidity in Early-Stage Breast Cancer Patients After Breast-Conservation Treatment [Journal of Clinical Oncology]
Purpose: Several studies have reported increased cardiac mortality related to the use of left-sided breast or chest-wall irradiation. This study was undertaken as a comprehensive examination of the long-term cardiac mortality and morbidity after breast irradiation using contemporary irradiation techniques.

Methods: The medical records of 961 consecutive patients presenting between 1977 and 1994 with stage I or II breast cancer treated with breast conservation treatment were reviewed. Data was recorded on baseline pretreatment patient, tumor and treatment characteristics and on subsequent cancer or cardiac related events. The median follow-up time was 12 years.

Results: There was no difference in overall mortality from any cardiac cause (P = .25). Death from any cardiac cause occurred in 2% of right-sided patients and 3.5% of left-sided patients. However, in the second decade after treatment, there was a higher rate of cardiac deaths in left-sided patients, with a cumulative risk of 6.4% (95% CI, 3.5% to 11.5%) for left-sided compared with 3.6% (95% CI, 1.8% to 7.2%) for right-sided patients at 20 years. There were statistically higher rates of chest pain, coronary artery disease, and myocardial infarction diagnosed in left-sided patients (all P .002). The presence of hypertension was associated with a higher risk of coronary artery disease in left-sided patients.

Conclusion: Irradiation to the left breast is not associated with a higher risk of cardiac death up to 20 years after treatment, but is associated with an increased rate of diagnoses of coronary artery disease and myocardial infarction compared with right breast treatment.


OPEN ACCESS: EDITORIAL: Which Breast Cancer Patients Should Really Worry About Radiation-Induced Heart Disease.And How Much? [Journal of Clinical Oncology]
The most difficult portion of my discussion with breast cancer patients about the potential adverse effects of radiation therapy (RT) is estimating their long-term chance of developing radiation-induced heart disease (RIHD). Very large studies combining tumor registry data with pre-existing regional or national hospital discharge diagnosis and death records and the Oxford meta-analyses of randomized trials found increased risks of coronary heart disease (CHD) for irradiated patients compared with nonirradiated ones, or for patients treated to the left breast or chest wall compared to those treated to the right side. However, most patients in these studies were treated with obsolete techniques that exposed much larger volumes of the heart to radiation than is done today, often with daily doses (fraction sizes) of 2.5 Gy or higher. Patients whose treatment was administered after 1975 to 1980 followed for median times of approximately 9 to 10 years had little or no increased risk of RIHD in these and additional registry and large clinical series (700 to 3,000 patients). For example, Giordano et al4 found that the 15-year risk of cardiac mortality for 8,652 patients treated from 1973 to 1979 was substantially higher when left-sided irradiation was administered than when right-sided irradiation was used (13.1% v 10.2%; P = .02). This absolute 15-year rate decreased substantially for 6,495 patients treated from 1980 to 1984 (9.4% v 8.7%, respectively; P = not significant), and there was further greater reduction for 12,136 patients treated from 1985 to 1989 (5.8% and 5.2%, respectively). Certainly, more patients in recent times have been treated to the intact breast without nodal irradiation, which eliminates cardiac irradiation entirely in most patients and, for those still exposed, reduces the irradiated volume. Improvements in treatment of CHD also no doubt played a major role in these absolute reductions in both laterality groups, a matter I will return to later.

These data have shortcomings. Coding of whether patients actually received RT or had a cardiac event may be inaccurate, particularly in registry studies or when death certificates are the main source of information. For example, Vallis et al14 found that 16% of myocardial infarctions coded in Ontario (Canada) hospital registries were not verifiable according to standard criteria when individual medical records were reviewed. Further, RIHD can take at least 15 to 20 years to develop, and few of these more recently treated patients have been followed that long. Nonetheless, I am reasonably certain that patients treated today on average will have a very low risk of RIHD.

My problem comes when trying to move beyond the average. For any one patient, the risk of RIHD seems likely to be a function of three variables: the cardiac "dose-volume histogram," the use of potentially cardiotoxic systemic therapy, and the presence and treatment of independent risk factors for CHD (such as hypertension, diabetes, cholesterol and lipid disorders, and smoking). Unfortunately, I do not have an equation at hand with which to make this calculation reliably.