If treated early enough, low-risk breast cancer patients who receive accelerated partial breast irradiation (APBI) after lumpectomy do just as well over the next decade as women treated with whole breast irradiation, researchers told the 2019 San Antonio Breast Cancer Symposium (Abstract GS4-06).
APBI was associated with significantly fewer adverse events and better cosmetic results than whole breast irradiation (WBI), without increasing the risk of ipsilateral breast tumor recurrence (IBTR) or death. The findings support the use of partial breast irradiation in carefully selected patients, lead author Icro Meattini, MD, of the University of Florence, Italy, told a press conference.
Recent developments in radiation oncology have shown a move toward radiation treatment de-escalation for early breast cancer, including accelerated and nonaccelerated partial breast irradiation, Meattini noted. The 10-year outcomes from the randomized phase III APBI IMRT Florence trial were similar to 5-year results, published in 2015.
"Postoperative radiation still represents a mainstay of adjuvant treatment...and is able to significantly reduce the local relapse occurrence rate," he said. "What we've learned from major phase III trials...is that [with partial breast radiation,] disease control is closely related to the adequate selection of patients," he said. "APBI might be considered a standard alternative to WBI in low-risk and very low-risk early breast cancer patients."
Study Details
Meattini and his associates analyzed 10-year follow-up data for 520 women enrolled in the trial who, between 2005 and 2013, were randomly assigned to receive either APBI or WBI. All of the patients were over 40 years of age with either stage 1 or stage 2 cancer. The majority of the patients had hormone receptor-positive, HER2-negative breast cancer, and most were over age 50.
Women treated with APBI received a total of 30 gray (Gy) of radiation to the tumor bed in five daily fractions, while WBI subjects received a total of 50 Gy in 25 daily fractions to the whole breast, plus a boost of 10 Gy to the tumor bed in five daily fractions. Both treatment arms were comparable in terms of age, tumor size, tumor type, and adjuvant endocrine treatment, and both achieved a median 10-year follow-up.
After 10 years, breast cancer recurred in 3.3 percent of women in the APBI arm versus 2.6 percent in the WBI group. However, this difference was not statistically significant and was comparable to the 5-year results. In the earlier analysis, APBI subjects had a 2.4 percent recurrence rate versus a 1.2 rate in the WBI women. Overall survival at the 10-year mark was also very similar, Meattini continued, with rates of 92.7 percent in the APBI group and 93.3 percent in women who received WBI. Breast-cancer-specific survival was 97.6 percent for the APBI cohort and 97.5 percent for women in the WBI arm of the trial, while the distant metastasis-free survival rate was 96.9 percent in both groups.
"These results reinforce the initial promising results from the previous study, that accelerated partial breast irradiation can produce excellent disease control," Meattini said. "Combined with data from other studies, the findings are part of a growing body of data that can help clinicians make better evidence-based recommendations to their low-risk breast cancer patients.
"In well-selected cases, there is no difference in patients' outcomes whether they are treated with APBI or WBI," he said. "A once-daily regimen of external APBI might also produce an improved quality of life, with less toxicity, and can potentially reduce the overall treatment time." APBI may also be less likely to cause cosmetic changes and is less expensive to administer than WBI, he added.
"Partial breast irradiation is one of the primary examples of effective de-escalation of treatment in breast oncology. For many patients, partial breast irradiation may be an optimal choice that is cost-effective, safe, and efficacious."
Methodology
Conducted from March 2005 to June 2013, the trial involved women with a maximum pathological tumor size of 25 mm who were randomly assigned in a 1:1 ratio to receive either WBI using 3-D conformal radiotherapy or APBI using intensity-modulated radiotherapy.
The 10-year follow-up included review of overall survival, breast cancer-specific survival, distant metastasis-free survival, contralateral breast cancer, and locoregional recurrences.
In all, 260 women participated in the APBI arm of the trial while 260 received whole breast treatment. All of the patients achieved median 10-year follow-up and all were comparable with regard to age, tumor size, grade, tumor type, and adjuvant endocrine therapy.
No significant difference in ipsilateral recurrence was found between the two treatment arms. Among women who received APBI, the 5-year IBTR was 1.96 percent (5 events) and the 10-year IBTR was 3.74 percent (9 events). In the WBI group the 5-year IBTR rate was 1.2 percent (3 events) and the 10-year rate was 2.5 percent (6 events). The hazard ratio for women in the APBI group versus WBI patients was 1.33, while the HR for APBI patients was 0.66.
The breast cancer-specific survival rate for subjects in the APBI arm was 98 percent, compared to 97.5 percent among women treated with WBI, while the distant metastasis-free survival rate for the APBI cohort was 97.4 percent compared with 96.1 in the other group. Locoregional recurrences were 3.9 percent in the APBI treatment arm versus 3.0 percent among women treated with whole-breast irradiation.
Cosmetic results were substantially better with APBI versus WBI, as measured by the Harvard Breast Cosmesis Scale, with significantly more physicians and patients having reported "good" or "excellent" outcomes.
Commentary
In addition to the current findings, a number of randomized clinical trials have reached similar conclusions, including phase III trials from the NSABP B-39 in the U.S., the RAPID trial in Canada, the U.K., and European Union, noted Gary Freedman, MD, Professor of Radiation Oncology at the University of Pennsylvania's Abramson Cancer Center.
"These have confirmed that the long-term overall survival is the same between whole breast and partial breast radiation for early-stage breast cancer, so I think this has been settled," he told Oncology Times.
Even so, he said there are several remaining issues to be considered. "There is some uncertainty over how broad we should make the eligibility. Early-stage disease, yes. But what about patients with larger tumor sizes, positive nodes, receptors negative, close margins, and other factors? A problem with many of the trials is they were highly selective for small, very favorable breast cancer in older women-in many cases, women who may not have needed radiation in the first place. Will the results of partial breast be as good if we open it up to more young women <50, with more adverse features to their breast cancers?"
Despite the positive results of these trials, partial irradiation has yet to be widely adopted in the U.S., according to Freedman, who estimated that it is only being used in treating perhaps 5 percent of eligible patients. Among the barriers to wider use is the need for more education of physicians about the procedure's safety and positive results.
"There is a typical inertia to overcome in having physicians change their patterns of care, especially if in the 80s, 90s, and 2000s, partial breast was not a routine part of radiation training."
Another big question, he continued, is whether or not cosmetic results are the same.
"The Florence trial researchers said the cosmetic results are as good between partial breast and WBI, while the Canadian trial said the opposite. We don't know what factors-size of the breast cancer, surgery technique, or radiation technique-determine how to get the best cosmetic result."
How radiation is paid for is another factor, he added. "It is currently paid for by the number of treatments-if whole breast radiation pays 16-30 treatments, there is a possible bias against changing to a Florence regimen of only five treatments. More patient education about this shorter and convenient option for radiation is needed so that they feel empowered to ask if it is right for them."
Kurt Samson is a contributing writer.