Boost may reduce effects of positive lumpectomy margins

LOS ANGELES—Adding a radiation therapy boost to the lumpectomy site after lumpectomy with whole-breast radiation therapy reduces the risk of local recurrence, particularly among breast cancer patients with high-risk features, including positive margins.

Speaking at the ASTRO annual meeting (abstract 4), lead author Heather Jones, MD, of the University of Pittsburgh, presented the updated 10-year results of the EORTC Boost–No Boost Trial, along with a look at risk factors for recurrence.

At the time of the study, Dr. Jones was at the Holzer Center for Cancer Care, Gallipolis, Ohio. Principal investigator is Harry Bartlelink, MD, of the Netherlands Cancer Institute.

"Our patients who opt for breast-conserving therapy vs mastectomy have a nontrivial risk for local recurrence," Dr. Jones said. "Preventing such a local recurrence is an important clinical parameter, as there is now evidence that local control is indeed linked to long-term survival in our early breast cancer patients."

Study patients had stage I or II breast cancer and underwent lumpectomy followed by whole-breast irradiation with 50 Gy. Thereafter, the 5,318 patients with microscopically completely excised tumors were randomly assigned to no additional treatment or to a 16-Gy boost, while the 251 patients with microscopically incompletely excised tumors were randomized to a 10-Gy or 26-Gy boost.

Ten-year results from the group with completely excised tumors (J Clin Oncol 25:3259-3265, 2007) showed that the 16-Gy boost significantly reduced the cumulative rate of local recurrence, compared with no boost (7% vs 12%, HR 0.59).

"Unlike our 5-year update, our 10-year update shows that this relative reduction by the boost is seen in all age categories. Still, the absolute benefit is greatly obtained by our young patients, particularly those 40 years old and less," Dr. Jones noted. At the same time, the boost significantly increased the rate of severe fibrosis (4.4% vs 1.6%).

To better define risk factors for ipsilateral recurrence, central pathology review was performed for about one-third of patients in the entire trial (regardless of excision status), Dr. Jones said.

The final margin status was classified as negative (no tumor on reexcision or a tumor-free zone ≥ 2 mm); close (tumor-free zone < 2 mm); or positive (tumor at the margin). She noted that the extent of margin positivity was not assessed.

Univariate analyses

In univariate analyses, the factors associated with a reduced rate of ipsilateral recurrence were age older than 50 years (HR 0.40), a boost (HR 0.54), and chemotherapy (HR 0.62), Dr. Jones said.

The factors associated with increased risk were DCIS at the margin (HR 1.27), high-grade DCIS associated with the tumor (HR 1.55), or a high grade of the invasive tumor (HR 2.08).

"Of note, margin involvement with invasive tumor or EIC [extensive intraductal component] presence was not significant," she said. The cumulative 10-year local recurrence rate did not differ significantly whether margins were negative, close, or positive for invasive tumor (6%, 8%, and 11%, respectively) but did differ according to marginal status for DCIS (8%, 10%, and 14%).

Receipt of the boost was associated with a significantly lower 10-year rate of local recurrence if margins were positive for invasive tumor (4% vs 13%) or DCIS (6% vs 15%); the boost had no such benefit for women with negative margins.

Multivariate analyses

In multivariate analyses, the 10-year risk of ipsilateral recurrence was reduced for women who were older than age 50 (HR 0.41) and received a boost (HR 0.56), whereas it was elevated for women who had high-grade DCIS associated with their tumor (HR 1.51) and an invasive tumor with high grade (HR 1.86).

"Of note, when variables of margin status were included in multivariate modeling, they were not found to be significant," Dr. Jones commented.

Receipt of a boost significantly lowered the risk of recurrence among the group with high-grade DCIS associated with their tumors (5% vs 17%) and the group with high-grade invasive tumors (7% vs 19%).

Summing up the findings, Dr. Jones said, "Age is the most striking risk factor associated with ipsilateral breast tumor recurrence." In addition, she said, a high grade of the invasive tumor appears to have a stronger impact than positive margins.

"A boost dose of radiation reduces the effect of involved margins and significantly lowers the risk of ipsilateral breast tumor recurrence in our patients with high-risk features," she concluded.