Smoking Ups Late Effects of Breast Cancer Radiation

Neil Osterweil

December 14, 2015

SAN ANTONIO — The risks for late lung cancer and ischemic heart disease among women who undergo irradiation for breast cancer are both reassuringly low, unless the patient is a smoker who just can't kick the habit, said investigators from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG).

"In our data, the main risks of breast cancer radiotherapy were cardiac mortality and lung cancer, and in nonsmokers, even taking those two risks together, the overall absolute risk was well under 1%, and that's good news for many women," said Carolyn Taylor, MD, a radiation oncologist at Oxford University in the United Kingdom.

"However, for one specific group of women — that is, long-term smokers who continue to smoke after their radiotherapy — the [absolute] risk of lung cancer may be a few percent, and that's because the risk of lung cancer is 20 times greater in a smoker than in a nonsmoker," she said at the San Antonio Breast Cancer Symposium (SABCS) 2015.

Dr Taylor and EBCTCG colleagues conducted meta-analyses of data on 40,781 women in 75 studies, with a median time of study entry of 1983. They compared 30-year risks for lung cancer and ischemic heart disease in women with breast cancer with or without radiotherapy.

To correct for now-outdated radiation therapy approaches in their estimation of patients' future risks for both lung cancer and ischemic heart disease, they substituted older data with new information on modern, tissue-sparing radiation techniques and lower overall doses to nonbreast tissues.

They calculated a 0.8% risk for lung cancer at age 80 years among women who received radiotherapy at age 50 years and received an average dose to the lungs of 5 Gy using older protocols, compared with 0.5% among women who did not undergo radiotherapy.

In contrast, among patients who smoked since adolescence, the 30-year risk for lung cancer would be 13.8% with radiation vs 9.4% for smokers who did not get radiation.

Similarly, the risk for ischemic heart disease was calculated to be 2.0% for irradiated nonsmokers who received a mean 2 Gy dose to the heart under older protocols and 1.8% for nonirradiated nonsmokers. For smokers, on the other hand, the risk of smoking plus irradiation or prior ischemic heart disease was 8.6% with radiation and 8% without.

The investigators determined that the average dose delivered to both lungs in the older trials was 10 Gy, compared with a 5-Gy standard dose or 3-Gy low dose in modern trials.

Radiation doses to the heart in older studies averaged 6 Gy compared with a 4-Gy standard dose and 2-Gy low dose today, they calculated.

The investigators next calculated the rate ratios from the trial and found that, for lung cancer after a minimum of 10 years' follow-up, the rate ratio was 2.10 for women randomly assigned to chemotherapy vs women assigned to no chemotherapy. The rate ratio for cardiac mortality was 1.30. Both rate ratios were statistically significant.

They determined that in the historical trials the excess rate ratio per gray was 12% for lung cancer and 4% for cardiac mortality.

"These excess rate ratios are likely to apply today," Dr Taylor said.

When they applied these excess rate ratios per gray to modern radiotherapy doses and modern population-based data, they found that for nonsmokers the combined risks of radiotherapy are less than 1%, but for women who started smoking in adolescence and continued to smoke throughout radiotherapy, the predicted risks were "a few percent."

Stopping smoking at the time of radiotherapy may avoid much of the risk Dr Carolyn Taylor

Their findings show that "smoking status can determine long-term effect of breast cancer radiotherapy on mortality, and stopping smoking at the time of radiotherapy may avoid much of the risk, and that's because most of the risk of lung cancer starts more than 10 years after the start of radiotherapy. So if a woman has radiotherapy when she is age 50, her risk from radiotherapy doesn't start until age 60. So if she stops smoking at the time of radiotherapy, then she has time to reduce her risks," she said.

A radiation oncologist who was not involved in the study tells Medscape Medical News that the data are not surprising but are reassuring.

"We learned the tough way about all these complications, and the kinds of complications they describe come from old techniques and old knowledge, while nowadays things have improved tremendously, not only in the technique, but in the tailoring of radiation to reflect how much we should respect the heart, and how can we use technology to spare the heart," said Alphonse Taghian, MD, chief of breast radiation oncology and codirector of the breast cancer research program at the Massachusetts General Hospital Cancer Center in Boston.

For example, radiation oncologists today carefully sculpt their radiation delivery when treating the internal mammary chain or supraclavicular to minimize the risk of excess doses to the lungs and esophagus, he said.

The study was sponsored by the EBCTCG. Dr Taylor and Dr Taghian have disclosed no relevant financial relationships.

San Antonio Breast Cancer Symposium (SABCS) 2015. Abstract S5-08. Presented December 11, 2015.


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