New Study Shows Higher CVD Mortality in Breast Cancer Patients Receiving RT

HAMBURG, Germany—Radiotherapy for breast cancer increases the risk of death from cardiovascular disease (CVD), compared with patients who did not receive such treatment, according to data from a large retrospective cohort study. Maartje Hooning, MD, a clinical epidemiologist from the Netherlands Cancer Institute, Amsterdam, and lead investigator of this study, presented the findings at the 4th European Breast Cancer Conference (abstract 291).

Dr. Hooning’s research team studied data from 7,247 patients with early breast cancer, who ranged from 17 to 71 years of age. These patients had been treated for stage I-III breast cancer and had been admitted to the Netherlands Cancer Institute or the Daniel den Hoed Cancer Center in Rotterdam between 1970 and 1987. Patients have been followed for a median of 14 years, and 34% have been followed for more than 20 years. For 92% of the patients, a complete medical status was available up to January 1998.

The investigators compared mortality from cardiovascular disease in patients receiving radiotherapy and nonirradiated patients. The study population’s cardiovascular mortality rates were than compared with those of the general female population. The team also clearly documented the sites of the radiation fields.

Compared with the general female population, the number of cardiovascular deaths in the study population was within the normal range of expectancy. Further analysis showed a 2.2-fold increase in cardiovascular deaths among patients who had received radiotherapy, compared with those who had not (range of risk, 1.4 to 3.6). "In terms of absolute excess risk, this means 12 extra cardiovascular deaths per 10,000 irradiated patients per year," Dr. Hooning said.

The nonirradiated group actually had a significantly lower cardiovascular mortality at 0.6-fold (range, 0.3 to 0.8) than the general female population, suggesting that the risk profile for breast cancer is protective against cardiovascular disease. Dr. Hooning explained this apparent anomaly by saying that a healthier life style after breast cancer may play a role.

"When you analyze the data, it is not such an unexpected development after all," Dr. Hooning said. "Breast cancer is linked with a higher socioeconomic status, which is associated with better nutrition, a lower risk of hypertension, and less obesity. So, as a result, breast cancer patients might indeed have a lower risk profile for cardiovascular disease." The diagnosis of cancer may also have led patients to improve their lifestyle. "Stopping smoking and losing weight through exercise and a healthy diet may contribute to the lower cardiovascular mortality rate," Dr. Hooning said.

The radiation-related risk increased dramatically among patients who had more than 10 years of follow-up. Patients treated before the age of 45 had an even greater radiation-related increased CVD risk [Standardized Mortality Ratio (SMR) = 2.6]. This increased risk is thought to be caused by the lower background risk of CVD in younger woman, compared with older woman.

The relative risk of CVD in woman who had received radiotherapy to their left chest wall was 1.6 times higher than the risk in patients receiving radiotherapy to the right side. Although not significant, this increase was probably a direct side effect of the radiotherapy, since radiotherapy on the left side affects a large part of the heart. This difference was especially noticed in woman who received radiation following mastectomy, compared with those irradiated after breast-conserving surgery.

"The good news is that the figures show that the risks of CVD with radiotherapy have decreased over time," Dr. Hooning said. The cardiovascular disease mortality rate for patients treated before 1980, for whom mastectomy was standard, was 1.9 times that of nonirradiated patients. For woman treated after 1980, this risk was down to 1.5 times that of nonirradiated patients.

This decrease in CVD deaths can be attributed partly to improvements in radiation therapy techniques and changes in the way radiotherapy is given. "Today, for example, radiotherapy to the parasternal field—the rectangular field along the breastbone—is given less frequently. But the findings also provide strong support for all the research being done on minimizing the radiation dose to the heart," Dr. Hooning said.

The research team is currently analyzing the incidence of CVD in the study population. Said Dr. Hooning, "It is expected that this will give us a more accurate view of CVD risk than does mortality. Even if we do not immediately notice any increased mortality risk in some patients, there may be an increased incidence because it may take years before cardiovascular events are ‘translated’ into actual deaths."