Radiotherapy Risks Can Outweigh Benefits for Breast Cancer Patients Who Smoke

Many women with breast cancer turn to radiotherapy, a proven treatment that reduces the risks of recurrence and death, but long-term smokers face a greater risk of lung cancer and cardiac mortality from radiotherapy, according to a study that performed a literature review and meta-analyses.

The study, published in the Journal of Clinical Oncology, examined the long-term hazards of radiotherapy, most commonly lung cancer and heart disease. The incidence of these diseases and their resulting mortality rates are significantly higher among smokers, so the researchers estimated risks of radiotherapy separately for both, women with breast cancer who smoke and those who do not.

To calculate these risks, the researchers first conducted a systematic review to establish the mean organ doses of modern breast cancer radiotherapy to the heart and the lungs. They then collected data from 75 radiotherapy trials that began before 2000, including on patient and tumor characteristics and mortality outcomes. The data did not include smoking status, so the excess rate ratios for the causes of death were based on all the women in the study.

The authors then multiplied these excess ratios per unit of radiation by the lung and heart doses, and applied them to the mortality rates from lung cancer and ischemic heart disease in current smoker and nonsmoker populations. This allowed for the calculation of the estimated risk of death from lung cancer or heart disease before age 80 years for women who never smoked, women who continued smoking since adolescence, and women who quit smoking at the time of radiotherapy.

Assuming a 50-year-old nonsmoker received a radiotherapy dose that increased lung cancer rates by 55%, her risk of lung cancer mortality before age 80 would rise from 0.5% to 0.8%, while a smoker receiving the same radiotherapy dose would see her lung cancer mortality risk before age 80 rise from 9.4% to 13.8%. If a woman quit smoking before starting radiotherapy, her radiation-related increase in lung cancer mortality would drop from 4.4% to 1.3%.

Similar patterns were observed from the estimates of heart disease mortality. The mean heart radiation dose multiplied baseline risks of cardiac death by 1.16, so the absolute risk of heart disease death would increase by 0.3% for a nonsmoker and 1.2% for a smoker. These risks varied with the size of the radiation dose.

The researchers emphasized that these findings strongly support smoking cessation, which could bring the excess risk of mortality closer to that among those who had never smoked. They also noted that the added risk of mortality from these diseases in smokers could outweigh the benefits of radiotherapy in reducing breast cancer mortality.

“These findings reinforce the need to limit lung and heart doses without unduly compromising the dose to the target tissues, and the need for smokers to stop smoking,” they wrote.

Smoking cessation is a major objective in oncology practice, as both the dangers of cigarettes and the benefits of cessation are greater in cancer patients, according to Paul M. Cinciripini, PhD, of the University of Texas MD Anderson Cancer Center, who delivered a presentation on the topic during the recent National Comprehensive Cancer Network’s 22nd Annual Conference. He explained that continuing to smoke during cancer treatment, including radiation, diminishes the effectiveness of the therapy while increasing symptom burden and the likelihood of cancer recurrence and mortality.