Smoking alters effects of radiotherapy on breast cancer mortality

The risks of radiotherapy for long-term smokers undergoing treatment for breast cancer outweighed the benefits, whereas for nonsmokers or exsmokers, the benefits far outweighed the risks, according to study results from the United Kingdom.

“The absolute hazards from modern breast cancer radiotherapy regimens for typical patients depend on the lung and heart doses from modern regimens, the excess rate ratios per Gy for lung cancer and heart disease, and further lung cancer and heart disease mortality rates in the general population,” Carolyn Taylor, DPhil, clinical research fellow at Nuffield Department of Population Health at University of Oxford, and colleagues wrote. “Women who smoke throughout adulthood have approximately 20 times the lung cancer mortality rates and four times the cardiac mortality rates of nonsmokers. Particularly for lung cancer, therefore, the absolute risks from breast cancer radiotherapy could be appreciable for smokers, even if they are small for nonsmokers. Hence, absolute risks of radiotherapy should be estimated separately for smokers and nonsmokers.”

The researchers performed a systematic literature review of breast cancer regimens published between 2010 and 2015, as well as a meta-analysis of 75 trials in which 40,781 women had been randomly assigned to either radiotherapy for breast cancer or no radiotherapy. Trial data did not include smoking status for the women.

Taylor and colleagues combined the excess risk ratios per Gy from the trials and literature review and applied them to the cancer and cardiac mortality rates of both smokers and nonsmokers using population-based data.

Among 647 regimens, patients received an average dose of 5.7 Gy for whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (IQR, 2008-2011).

Ten years or longer after radiotherapy, patients demonstrated an excess rate ratio per Gy of 0.11 (95% CI, 0.05-0.2) for lung cancer and .04 (95% CI, 0.02-0.06) for cardiac mortality.

Long-term smokers experienced higher absolute risk for lung cancer (4% vs. 0.3%) and cardiac mortality (1% vs. 0.3%) than nonsmokers.

Given these findings, “the incorporation of smoking cessation programs for smokers with newly diagnosed breast cancer assumes paramount importance,” Simona F. Shaitelman, M.D., Ed.M., assistant professor in the department of radiation oncology at the University of Texas MD Anderson Cancer Center, and colleagues wrote in an accompanying editorial.

“Although the study by Taylor [and colleagues] is likely one of the largest local therapy meta-analyses ever conducted … the key findings underscore the need to personalize care for patients with breast cancer through vigorous promotion of smoking cessation, judicious radiation treatment planning and careful minimization of radiation target volume in an evidence-based manner,” Shaitelman and colleagues wrote. “Through these efforts, late radiation toxicity can be almost entirely avoided in all patients, with the exception of smokers who continue to smoke.”– by Andy Polhamus

Disclosure: Taylor reports payment for expert testimony for the Crown Prosecution Service. Please see the full study for a list of all other researchers’ relevant financial disclosures. Shaitelman reports consultant or advisory roles with MD Anderson Cancer Center and research funding from Elekta. Please see the editorial for a list of all other author’s relevant financial disclosures.