Radiation has long been a mainstay of breast cancer treatment, and following surgery up with the therapy can reduce the risk of recurrence. The drawback of radiation, though, is a fistful of unpleasant potential side effects including pain, a slight risk of organ damage, a very small risk of secondary cancer, and the time and money needed for the procedures. Now the results of a Phase 3 trial suggests that many older patients may not need radiation and can go without it after surgery without harming their overall survival.
“It’s remained controversial for a number of years,” said Ian Kunkler, a clinical oncologist at the University of Edinburgh and the lead author on the study, published in the New England Journal of Medicine. “There was particular interest as to whether that might be omitted in older patients. There is a nonspecific fatigue that most patients encounter during radiotherapy and sometimes for several weeks afterwards, and that can be particularly burdensome to older patients, particularly if they have other comorbidities.”
Part of the debate is that the vast majority of the trials studying radiation didn’t include patients over the age of 65, who represent more than half of the patients Kunkler sees in the breast clinic. So he and his colleagues designed a randomized clinical trial to test if radiation truly made a difference for some of those patients, specifically those with smaller tumors that were less likely to be aggressive.
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The results of this study, along with an earlier trial called CALGB 9343 that tested omitting radiation for breast cancer patients 70 years or older, provided further evidence that radiation may not impact the overall survival of older patients with small, low-risk tumors. The study showed that the therapy did, however, reduce the risk of cancer returning in the same breast by 10-fold. That was even higher for patients who had tumors that didn’t strongly express estrogen receptors. That means the study raises key questions around the decision to omit radiation, experts said, and which patients can truly do so safely.
“How you make that decision has changed. There are nuances that we didn’t ask, the patient didn’t ask, in the past like the degree of estrogen receptor positivity and what types of regimens your radiation oncologist offers,” said Alice Ho, the co-director of the breast clinical research unit at Duke University Medical Center who wrote an accompanying editorial in NEJM but did not work on the trial. “I think this trial will change much. It demonstrated details not available before.”
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To do the study, Kunkler and his colleagues recruited 1,326 women 65 years old or older to the study. All of them had a tumor that was 3 centimeters wide or less and hormone-receptor positive. All the patients had surgery to remove the tumors and then half received radiation, while the other half went without it. Afterwards, most of the patients received endocrine therapy for five years that reduces the risk of recurrence.
“Overall survival was 80% in both groups. That’s an important finding — no compromise in overall survival,” Kunkler said. “Most patients were not dying of breast cancer. It was other causes — nearly 10% of cardiac causes and over 20% from other cancers.”
There was also no difference in distant spread — recurrence in areas other than the breast — between both groups, but radiation mattered when it came to recurrence in the same breast. Overall, those who received the radiation had a 0.9% risk of local recurrence, while those who didn’t get irradiated had a 9.5% risk of the cancer returning in the same breast.
But there were two key caveats. When patients had tumors with weaker estrogen receptor expression — or when the estrogen receptor was not as present on cancer cells — forgoing radiation had a much bigger impact. Of those patients, 19.1% saw their cancers return in the same breast after 10 years. “The other interesting analysis was in women who were in the radiation arm and did not adhere to 5 years of endocrine therapy,” Naamit Gerber, a radiation oncologist at NYU Langone Perlmutter Cancer Center who did not work on the trial, wrote in a statement. “Local recurrence was over 4 times higher in these women.”
Endocrine or hormonal therapy, like the drug tamoxifen, reduces the likelihood that breast cancer will return for patients who have hormone-positive tumors. The downside is that it can be difficult to tolerate the side effects of endocrine therapy, which include menopause-like symptoms, nausea, weight gain, and more. “Thus, caution must be exercised in omitting radiation” for these patients, Gerber wrote.
Radiation, Duke’s Ho said, has also gotten far easier and safer in recent years as well. The risk of damage to nearby organs like the lungs or heart has gone down, and patients can complete modern radiotherapy in as few as five days, whereas in the past it may have taken several weeks. “Even if radiation does not change survival for an older woman, many may say, ‘If it cuts down my risk of local recurrence, and I can do it in five days without burdening my life, then very well,’” Ho said.
That means patients must weigh the decision to skip radiation carefully and decide which course of action seems the most acceptable to them. “Where do they see themselves in five to 10 years from diagnosis, and what’s the most important goal for them?” She said. “If they are worried about cancer returning, which patients are concerned about, then what is the percent recurrence rate that is important to them? It’s about tailoring the treatment and customizing it to the patient’s disease and preferences.”