Breast Radiation for Cancer Raises Heart Disease Risk

March 6, 2007

AMSTERDAM -- Irradiation of the breast and internal lymph nodes for cancer puts women at increased risk for cardiovascular disease, reported investigators here.

AMSTERDAM, March 6 -- Irradiation of the breast and internal lymph nodes for cancer puts patients at increased risk for cardiovascular disease, reported investigators here.

Among more than 4,400 women who were 10-year survivors of breast cancer, those in the 1980s who had radiation to the internal mammary chain had an increased risk for congestive heart failure, reported Flora E. van Leeuwen, Ph.D., of the Netherlands Cancer Institute, and colleagues.

Irradiation of the breast alone was not associated with an increased risk for cardiovascular disease, they added.

The combination of radiotherapy and chemotherapy nearly doubled the risk for congestive heart failure, and irradiated patients who smoked had a three-fold risk for myocardial infarction, the investigators reported in the March 7 issue of the Journal of the National Cancer Institute.

"Apart from the clear benefits of adjuvant radiotherapy, physicians should be still aware of the potentially increased risk of cardiovascular disease following specific radiotherapy regimens in long-term breast cancer survivors," they wrote.

Although the authors found an increased risk of breast cancer, as was seen in earlier studies of patients irradiated under older protocols, it also shows that the degree of risk has diminished over time, wrote Sharon H. Giordano, M.D., M.P.H., and Gabriel N. Hortobagyi, M.D., of the University of Texas MD Anderson Cancer Center in Houston, in an accompanying editorial.

"Thus, although patients who were diagnosed between 1970 and 1979 with radiation to the left chest wall or to right or left internal mammary fields had an increased risk of myocardial infarction, overall, the patients who were diagnosed between 1980 and 1986 did not," the editorialsts wrote. "Although these analyses are reassuring, they do not directly address the shorter follow-up for the more recent cohort, and differences could continue to emerge with longer follow-up."

Dr. van Leeuwen and colleagues looked at the treatment-specific rate of cardiovascular disease in 4,414 women who were 10-year survivors of breast cancer who were treated from 1970 through 1986.

They compared cardiovascular disease risk in the cohort with general population rates, and created Cox proportional hazards regression models/

They found that after a median follow-up of 18 years, there were a total of 942 cardiovascular events. The standardized incidence ratio was 1.30 (95% confidence interval, 1.22 to 1.38). This corresponded to an excess of 62.9 cases per 10,000 patient years.

When they evaluated women who had received radiation from 1970 to 1979 to either the left or right side of the internal mammary chain, they found the treatment was associated with increased cardiovascular disease risk. In these patients, compared with patients who did not undergo radiotherapy, the hazard ratio for myocardial infarction was 2.55, (95% CI, 1.55 to 4.19, P

In their editorial, Dr. Giordano and Dr. Hortobagyi noted that other therapies, such as chemotherapy with anthracyclines, and targeted therapy with trastuzumab (Herceptin) also carry the risk of long-term cardiotoxicities.

"Some long-term toxicities such as left ventricular dysfunction may be delayed or prevented when diagnosed in an early or asymptomatic phase whereas others, such as valvular dysfunction may be challenging to prevent," they wrote. "Ultimately, we will need to be able to identify patients who are at high risk or with early signs of cardiac disease and to develop effective interventions to prevent the development of late toxicities and minimize their effects on quality of life."

Study limitations include possible differences in baseline cardiovascular risk in the treatment and comparison population. The authors were also unable to determine the dose of radiation to the heart for the treated patients.