SAN ANTONIO (FRONTLINE MEDICAL NEWS) – The late side effects of modern radiation therapy for breast cancer depend in part on a woman’s smoking status, suggests a meta-analysis of data from more than 40,000 women presented at the San Antonio Breast Cancer Symposium.

For nonsmokers, radiation therapy had little impact on the absolute risks of lung cancer or cardiac death, the main risks identified, which combined totaled less than 1%, Dr. Carolyn Taylor reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group. But for women who had smoked throughout their adult life and continued to do so during and after treatment, it increased that absolute risk to roughly 2%.

“Smoking status can determine the net long-term effects of breast cancer radiotherapy on mortality. 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 radiotherapy,” said Dr. Taylor, a radiation oncologist at the University of Oxford (England).

Radiation therapy remains an important tool in treating breast cancer, ultimately reducing the likelihood of death from the disease, she reminded symposium attendees. “The absolute benefit in women treated according to current guidelines is a few percent. Let’s remember the magnitude of that benefit as we think about the risks of radiotherapy.”

Attendee Dr. Steven Vogl of Montefiore Medical Center, New York, asked whether information was available on the location of the lung cancers that occurred in the trials.

“We didn’t have location of lung cancers. We didn’t even know if it was ipsilateral or contralateral to the previous breast cancer in this study,” Dr. Taylor replied. “But we’ve done other studies where we have known the location of the lung cancer, and there were similar findings in those studies.”

“In the last 4 years, we’ve had very good information that annual CT screening substantially and very quickly reduces the mortality from lung cancer,” Dr. Vogl added as a comment. “Any of us who care for patients who have been radiated where, really, any lung has been treated, who continue to smoke, should be screened – and screened and screened and screened again,” he recommended.

The investigators analyzed data from 40,781 women with breast cancer from 75 randomized trials conducted worldwide that compared outcomes with versus without radiation therapy. The median year of trial entry was 1983. On average, women in the trials received 10 Gy to both lungs combined and 6 Gy to the heart.

Comparing women who did and did not receive radiation therapy, the rate ratio for lung cancer was 2.10 at 10 or more years out, and the rate ratio for cardiac mortality was 1.30 overall. Given the mean radiation doses in the trials, the excess risk translated to 12% per Gray for lung cancer and 4% per Gray for cardiac mortality. “These rate ratios are likely to apply today,” Dr. Taylor maintained.

However, she noted, contemporary breast cancer radiation therapy techniques are much better at sparing normal tissues. To derive absolute risk estimates that are relevant today, she and her colleagues reviewed the literature for 2010-2015 and determined that women now receive an average of 5 Gy to both lungs combined and 4 Gy to the heart, with some centers achieving even lower values.

Among nonsmokers, the estimated cumulative 30-year risk of lung cancer was 0.5% for women who did not receive radiation therapy and 0.8% for those who received radiation therapy with a mean dose of 5 Gy to both lungs combined, Dr. Taylor reported. However, among long-term smokers, it was 9.4% without radiation and a substantially higher 13.8% with it.

Similarly, among nonsmokers, the estimated cumulative 30-year risk of ischemic heart disease death was 1.8% for women who did not receive radiation therapy and 2.0% for women who received radiation therapy with a mean dose of 2 Gy to the heart. Among long-term smokers, it was 8.0% without radiation and a slightly higher 8.6% with it.

Additional analyses looking at other late side effects showed no radiation therapy–related excess risk of sarcomas, according to Dr. Taylor. The risk of leukemia was increased with radiation, but actual numbers of cases were very small, she cautioned.

Attendee Dr. Pamela Goodwin, University of Toronto, said, “I’m just wondering whether you considered if it was valid to assume that there was a linear relationship between radiation dose and the risk of lung cancer in the range of radiation doses that you looked at, so, from the higher range in the earlier studies to the much lower dose now.”

Numbers of heart disease events were sufficient to establish a linear relationship, according to Dr. Taylor. Numbers of lung cancers were not, but case-control studies in the literature with adequate numbers have identified a linear relationship there, too. “We use what we can, and we have got now several hundred events, if you combine all of the literature together. And they do suggest the dose-response relationship is linear, but we can’t know that for certain,” she said.


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