Radiotherapy for Breast Cancer Harmful in Smokers  

Fran Lowry

March 29, 2017

Life-threatening toxicity from breast radiation in patients with breast cancer can be substantially reduced by smoking cessation, according to new research.

In a study published in the Journal of Clinical Oncology, smokers treated for breast cancer had much higher risks than nonsmokers for developing lung cancer or heart disease as a result of radiotherapy.

For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits Dr Carolyn Taylor

"For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits," lead author, Carolyn Taylor, DPhil, radiation oncologist at the Nuffield Department of Population Health, Oxford University, United Kingdom, said in an interview.

"Yet for most nonsmokers and ex-smokers, the benefits of radiotherapy far outweigh the risks," she added.

Dr Carolyn Taylor

"For nonsmokers, the absolute risk of death from the side effects of modern radiotherapy is only about 0.5%, which is much less than the benefit. But for smokers, the risk is about 5%, which is comparable with the benefit," Dr Taylor, who led the study on behalf of the Early Breast Cancer Trialists' Collaborative Group, told Medscape Medical News.

"Most patients seen in my cancer center and many other cancer centers are nonsmokers or ex-smokers, and for those patients the benefits of radiotherapy are likely to far outweigh the risks, so I find our results very reassuring. And even for patients who are long-term smokers, they can substantially reduce their risks from radiotherapy by giving up smoking at the time of radiotherapy. That's a very practical, useful message for us in the clinic," she said.

That's a very practical, useful message for us in the clinic. Dr Carolyn Taylor

Another important message to emerge from the study, which looked at lung and heart radiation doses and risks among more than 40,000 women with breast cancer worldwide, is the importance of using radiotherapy techniques that spare the lungs and the heart as much as possible, Dr Taylor said.

"In many countries, lung and heart doses are already very small, but in our study we found that they varied substantially throughout the world. So lung and heart doses in some cancer centers from breast cancer radiotherapy are tiny, but in other cancer centers they are much higher. The message for the cancer centers with higher doses is to use techniques that tend to spare the heart and spare the lungs," she said.

Study Provides a Guide to Decision Making

Writing in an accompanying editorial, Benjamin D. Smith, MD, from the University of Texas MD Anderson Cancer Center, Houston, and his colleagues note that the "nuanced findings" from the study "provide valuable and clear information with which to guide decision making."

Dr Benjamin D. Smith

They commend the authors for moving beyond their initial finding that women who received radiation experienced a 3.1% absolute excess risk for non–breast cancer mortality.

"If this estimated excess risk of death were applicable to current patients with early-stage breast cancer, then the appropriateness of radiation should be questioned. However, Taylor et al demonstrate that the risks of late radiation morbidity and mortality for patients treated with modern radiotherapy techniques are considerably lower than might be assumed on the basis of their unadjusted, aggregated data," the editorialists write.

In an interview with Medscape Medical News, Dr Smith praised Dr Taylor and her group for using current data to update risk estimates for radiotherapy for breast cancer.

"They did a very thoughtful job to take all the data that we have and supplied us with updated risk estimates surrounding radiotherapy outcomes in the modern era with modern treatments. I thought it was a great study," he said.

Late radiation toxicity can be almost entirely avoided in all patients with the exception of smokers who continue to smoke. Dr Benjamin D. Smith

"Late radiation toxicity can be almost entirely avoided in all patients with the exception of smokers who continue to smoke, especially with modern radiotherapy," Dr Smith said.

Three-Part Study

In the study, which was done in three parts, the researchers first reviewed the literature for all studies reporting lung and heart radiation doses in breast cancer radiotherapy published between 2010 and 2015.

They then did individual-patient-data meta-analyses of 40,781 women with breast cancer randomly assigned to radiotherapy or no radiotherapy in 75 trials to obtain rate ratios (RRs) per dose (Gy) for second primary cancers and cause-specific mortality and excess rate ratios (ERRs) per Gy for incident lung cancer and cardiac mortality.

Third, the researchers combined the risks per Gy in the trials that used modern doses and then applied those risks to determine the absolute risks for lung cancer and heart disease for smokers vs nonsmokers today.

Wide Variation of Radiation Doses

The radiation doses for lung and breast varied widely among the 647 regimens that were published during 2010 to 2015. The median year of irradiation was 2010 (interquartile range [IQR], 2008 to 2011).

The average modern whole-lung dose was 5.7 Gy (IQR, 3.4 to 8.3 Gy).

Average whole-heart doses were as follows: left-sided, 5.2 Gy (IQR, 1.9 to 7.4 Gy), and right sided, 3.7 Gy (IQR, 1.2 to 5.0 Gy). With these values averaged, the typical modern whole-heart dose was 4.4 Gy.

The researchers found that the estimated absolute risks from modern radiotherapy for lung cancer was approximately 4% for long-term continuing smokers and 0.3% for nonsmokers. For cardiac mortality, the ERRs were approximately 1% for smokers and 0.3% for nonsmokers.

Additionally, the ERRs for contralateral breast cancer and esophageal cancer were low.

"We think the risk for contralateral breast cancer from today's radiotherapies is likely to be tiny. We are much better at treating breast cancer today with surgery and chemotherapy and hormones. Similarly for cancer of the esophagus. We think the risk today is going to be pretty small. We did not have enough events to look at a dose-response relationship for esophagus cancer, but nowadays, we tend to angle the beams away from the esophagus; we don't include it in the field at all, so risk for esophagus cancer today is likely to be small," Dr Taylor said.

Smoking Cessation Programs Key

Given these key findings, the incorporation of smoking cessation programs for smokers with newly diagnosed breast cancer assumes paramount importance, Dr Smith said.

"Emphasizing the importance of smoking cessation is very important because the data indicate that there's a synergy in the risk of lung cancer between radiation and smoking, so certainly, you want to try to minimize those risks by getting your patients to quit smoking if at all possible. When we treat breast cancer with radiation, typically there is a little bit of lung in the path of the beam and that can be very mildly carcinogenic. That carcinogenicity is potentiated by smoking, so it's really the smokers who continue to smoke who are at risk of radiation associated lung cancers," he said.

"If you are not a smoker, the risk is essentially trivial, but if you are a smoker you are already at elevated risk of developing lung cancer, and then you add on some radiation on top of that and then those are the patients who have a clinically meaningful risk of radiation-induced lung cancer," Dr Smith said.

Older data from older clinical trials showed that radiation therapy increased the risk of dying from heart disease and lung cancer, and this has always provoked concern, he added.

"Particularly amongst non–radiation oncologists, there were fears that we were sending patients for a treatment which, although in the short run may be beneficial, in the long run would be a Pyrrhic victory because you cure the cancer only to kill the patient from something else. But this was from old data using antiquated, very poor radiation techniques," Dr Smith said.

"What this study says is if you have breast cancer today and you come and see me at MD Anderson and I have a great treatment machine and a great treatment team, and we know what we're doing, your risk of heart disease from radiation is very low, your risk of having lung cancer from radiation is very low, so we can give you the same benefits from radiation but we can really cut down on your risk. But only if you stop smoking," he said.

We can really cut down on your risk. But only if you stop smoking. Dr Benjamin D. Smith

Programs to help patients quit smoking are very important because it is extremely difficult for some people to quit on their own, Dr Taylor added.

"It's really hard to stop smoking, and it's especially hard when you've just been diagnosed with cancer. Many centers do not have the resources to help patients quit. Dr Smith has resources in his center and that's great, but they're not available to everybody," she said.

"We can advise our patients to give up smoking, but without support, it often doesn't work. Just acknowledging the difficulty and then recommending help for people who want support is a good way to go forward," Dr Taylor said.

Dr Taylor reports giving expert testimony to Crown Prosecution Service with monies donated to charity; Dr Smith reports that he receives research funding to his institution from Varian Medical Systems.

J Clin Oncol.  Published online March 20, 2017. Study full text, Editorial

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