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A low-dose radiotherapy (RT) boost to the tumor bed provided adequate control of breast cancer recurrence in younger patients with better cosmetic results as compared with a high-dose boost, long-term follow-up from a randomized trial showed.

The 10-year rate of locoregional recurrence (LR) was 4.4% with the low boost and 2.8% with the high boost. Patients in the low-dose group had a 27% incidence of marked or moderate fibrosis in the boost area versus 48% of patients treated with the high boost.

Although the difference in recurrence rate achieved statistical significance, the small absolute difference does not justify the greater impact on cosmesis with the high-dose boost, reported Sophie Bosma, MD, of the Netherlands Cancer Institute in Amsterdam, at the European Breast Cancer Conference in Milan.

"In both groups local recurrence rates were very low and much better than expected," Bosma said in a statement. "Although we did find a difference between the two groups in terms of recurrence rate, this was a small difference, which must be weighed against the increase in side effects, such as fibrosis. Knowing the long-term impact of a treatment on cancer control as well as on unwanted side effects is crucial in helping individual patients get the best possible treatment."

Radiotherapy has a key role in breast cancer treatment, especially in young women who have a higher risk of recurrence, said Michail Ignatiadis, MD, PhD, of the Institut Jules Bordet in Brussels.

"This important study provides critical information for the optimal boost radiotherapy dose for achieving local control without compromising the cosmetic outcome," said Ignatiadis, who did not participate in the study.

A radiation boost dose to the tumor bed in addition to whole-breast irradiation reduces local recurrence, Bosma noted. Given that young age is a risk factor for LR, investigators at 32 centers in the Netherlands, France, and Germany conducted the Young Boost trial to determine whether a higher boost dose would improve LR control in young patients undergoing breast conserving surgery.

"We know that in young patients, there is a higher chance of the breast cancer returning in the same place following breast-conserving treatment," said Bosma. "In this trial we were aiming to lower that risk by giving patients a high radiotherapy boost directed at the site of the tumor. We were also comparing a higher and lower dose to see which one worked best for young patients in terms of local control and cosmetic outcome."

From 2004 to 2011, investigators enrolled 2,421 patients age 50 or younger with pT1-2 pN0-2a invasive breast cancer and microscopically complete excision. Patients were randomized to an RT boost dose of 26 or 16 Gy to the tumor bed. The primary endpoint was local control at 10 years, and the trial protocol assumed a 3.5% difference. All new ipsilateral tumors were considered LR.

Baseline characteristics were well balanced, Bosma said. Median age was 45, median tumor diameter was 15 mm, and 70% of tumors were pN0. More than 80% of the patients had grade 2/3 tumors, and cancer subtype distribution was HR+/HER2- in 67%, triple-negative in 20%, and HER2+ in 13%.

Two-thirds of patients were treated with a sequential boost and the rest with a simultaneously integrated boost. Boost techniques consisted of x-ray beam in 75%, electron in 20%, 1% interstitial boost, and 4% other. In 82% of cases, patients received systemic therapy.

A total of 109 locoregional recurrences occurred during a median follow-up of 11.7 years, 61 in the low-boost group and 48 in the high-boost group. LR was the first event in 42 patients with low-dose and 23 with high-dose boost. The 1.6% absolute difference in LR at 10 years represented a 39% reduction in the hazard ratio (95% CI 0.39-0.96, P=0.032). By multivariable analysis, independent predictors of LR were boost dose, final surgical margin, cancer subtype, and use of chemotherapy.

"The primary endpoint that a high radiation boost after whole-breast irradiation improves local control by at least 3.5% was not met," the investigators concluded. "The small statistically significant benefit does not justify the increased impact on cosmetic outcomes."

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