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In Reply

Division of Radiation Oncology, Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

Dr Gyenes correctly assesses that despite examining detailed information on 961 patients, it remains unclear from our study which patients who received left-sided treatment specifically are at elevated risk for late cardiac toxicity.¹ In addition, our study period predates the routine use of both three-dimensional treatment planning and the use of doxorubicin-based adjuvant chemotherapy and adjuvant trastuzumab—factors which likely modify the cardiac disease risk profile after breast cancer treatment. We are in the process of examining technical treatment factors among our cohort in order to stratify risk by the estimated volume of heart included in these two-dimensional era plans. However, we expect these data to reveal a correlation between larger heart volumes and the risk of cardiac disease. Previous studies have confirmed that as the volume of heart irradiated increases the risk of post-treatment ischemia increases, although how this translates into long-term risk of cardiac disease is not precisely known.²

The natural question that arises from our study and other similar studies is indeed what modifying approach should be taken to reduce the risk of cardiac disease resulting from treatment, both in patients undergoing treatment today and in patients who have already received left-sided irradiation. Reducing the volume of irradiated heart and coronary arteries is an obvious answer, but may not be sufficient to normalize the risk of patients who received left-sided irradiation to that of patients who received right-sided irradiation.

We examined a large number of risk factors for cardiac risk and their interactions with heart irradiation, including lipid profiles, other systemic diseases such as diabetes, hypertension, and thyroid disease, alcohol and tobacco history, and family history. Of these, only hypertension appeared to interact with radiation to further increase the risk of cardiac morbidity in patients who received left-sided irradiation. Among the risk factors we examined between the right- and left-sided irradiated patients was the Framingham absolute risk score at the time of breast cancer diagnosis, which we calculated from the medical record review. We had complete data on 38% of the patient cohort, which showed an equivalent predicted 10-year risk of coronary disease between the right- and left-sided irradiated patients at baseline (6.7% for right-side and 7.1% for left-side irradiated patients, P = .48). In our study, there was no significant association between laterality and Framingham score and the risk of cardiac death or morbidity.

Dr Gyenes' suggestion that baseline Framingham score be used to stratify patients for treatment arms in a randomized trial using some kind of modifying treatment is intriguing, although the findings from our study did not show Framingham score to be predictive of increased cardiac risk after left-sided irradiation. Still, this or some other measure may be appropriate to stratify patients for prospective statin therapy intervention in the setting of a trial. Given our findings with respect to high blood pressure, antihypertensive management is another potential modifiable risk factor to be studied. It would also be useful to establish markers of cardiac damage that could monitor patients' cardiac status during and after radiation treatment, and to use noninvasive monitoring post-treatment to verify the validity of these tests and interventions. Through such studies it may be possible to further reduce cardiac risk after irradiation and provide more accurate recommendations to breast cancer patients regarding their long-term follow-up care.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Harris EE, Correa C, Hwang W-T, et al: Late cardiac mortality and morbidity in early stage breast cancer patients after breast conservation treatment. J Clin Oncol 24:4100-4106, 2006[Abstract/Free Full Text]

2. Marks LB, Yu X, Prosnitz RG, et al: The incidence and functional consequences of RT-associated cardiac perfusion defects. Int J Radiat Oncol Biol Phys 63:214-223, 2005[CrossRef][Medline]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Harris, E. E.R. Search for Related Content PubMed Articles by Harris, E. E.R. Social Bookmarking                            What's this?