Long-term data solidify partial-breast RT as standard of care in low-risk early breast cancer

In patients with low-risk, early-stage breast cancer who have undergone breast-conserving surgery, partial-breast radiotherapy (RT) is as safe and efficacious as whole-breast RT, according to 10-year data from the phase III IMPORT LOW trial.

Over a median follow-up of 120 months, the 10-year ipsilateral breast tumour recurrence (IBTR) rate was 2.8 percent among patients who received whole-breast RT (control) vs 3.0 percent among those who received partial-breast RT (unadjusted hazard ratio [HR], 1.06, 95 percent confidence interval [CI], 0.55–2.05) and 1.9 percent among those who received reduced-dose RT (unadjusted HR, 0.64, 95 percent CI, 0.30–1.36). [Lancet Oncol 2025;doi:10.1016/S1470-2045(25)00194-9]

Ten-year recurrence-free interval was also comparable across the three RT groups, being observed in 93.1 percent of patients in the whole-breast, 92.6 percent in the partial-breast, and 94.0 percent in the reduced-dose group. The same was true for the rates of 10-year breast cancer-free-interval (90.0 percent, 90.0 percent, and 91.6 percent, respectively) and 10-year distant recurrence-free survival (86.9 percent, 89.8 percent, and 85.9 percent, respectively).

Overall, 11 percent of the patients died, with breast cancer being the cause in 3 percent. The 10-year mortality rate was 12.3 percent in the whole-breast group, 9.8 percent in the partial-breast group, and 13.1 percent in the reduced-dose group.

Clinician-reported moderate-to-marked late adverse effects (AEs) were very low. The most common was breast shrinkage, occurring in 9 percent of patients in the whole-breast group, 7 percent in the partial-breast group, and 9 percent in the reduced-dose group. Few patients had breast oedema, and the percentage was slightly lower in the partial-breast group than in the whole-breast group (1.7 percent vs 3.6 percent).

Rib fractures, symptomatic lung fibrosis, and ischaemic heart disease were documented in ≤1 percent of patients across the three RT groups.

IMPORT LOW included 2,016 patients (median age 63 years) who had had breast conservation surgery for unifocal invasive ductal adenocarcinoma, pT1–2 (tumour size ≤3 cm), N0–1 (none to three positive axillary nodes), grades 1–3, with microscopic margins of noncancerous tissue of at least 2 mm.

The patients were randomly allocated to the whole-breast (n=675), partial-breast (n=669), or reduced-dose RT group (n=674). Patients in the whole-breast group received 40 Gy in 15 fractions to the whole breast; those in the reduced-dose group received 40 Gy in 15 fractions to the area of the breast where the cancer used to be and 36 Gy in 15 fractions to the rest of the breast; and those in the partial-breast group received 40 Gy in 15 fractions to the area of the breast where the cancer used to be. Treatment was administered daily over 3 weeks. 

Straightforward standard of care

“To our knowledge, IMPORT LOW is the first phase III trial reporting 10-year outcome data for local recurrence and AEs following partial-breast radiotherapy delivered using simple tangential external beam RT techniques,” which are particularly “straightforward to implement,” according to the investigators.

The 10-year data support the 5-year IMPORT LOW findings published in 2017 and align with data from other randomized controlled trials of partial-breast radiotherapy reporting local control outcomes at a median follow-up of 6–10 years. [Lancet 2017;390:1048-1060; Lancet 2019;394:2155-2164; Lancet 2019;394:2165-2172; J Clin Oncol 2020;38:4175-4183]

Already, partial-breast irradiation is a guideline-recommended de-escalation strategy option for RT in patients with low-risk, early-stage breast cancer. And the 10-year IMPORT LOW results “reaffirm the use of partial-breast RT delivered with intensity-modulated RT in this population as standard of care,” the investigators said.

“The rationale for including a reduced-dose group was that, had the partial-breast group been found to have inferior local control, the reduced-dose technique might have been adoptable instead. However … the reduced-dose technique offers no advantages over the partial-breast technique and is more complex to plan and deliver,” they continued.

De-escalation and adverse events

In a linked editorial, Drs David Krug and Jürgen Dunst, both from the University Medical Center Schleswig-Holstein in Kiel, Germany, pointed out that the focused delivery of radiation in a partial-breast RT regimen has not consistently translated to substantial decrease in late AEs. [Lancet Oncol 2025;doi:10.1016/S1470-2045(25)00216-5]

“Partial-breast irradiation exclusively treats the tumour bed, along with a circumferential safety margin. Nonetheless, despite the more focused approach of this treatment compared with whole-breast RT, trials have not consistently shown a clinically relevant reduction in late adverse events with partial-breast irradiation. The same is true for IMPORT LOW and might, in part, be explained by the simple tangential technique being used,” Krug and Dunst said.

“In patients with tumours in the upper breast quadrants, [for instance,] delivery of partial-breast irradiation with a simple tangential technique will lead to an incidental dose in the axilla, which is of importance in the context of recent trials on the omission of sentinel lymph node biopsy. Whole-breast RT is typically recommended in this situation, and further research is needed to establish whether partial-breast irradiation is oncologically safe in this setting,” they continued.

Notably, in the Danish Breast Cancer Group’s trial, which employed a fractionation regimen and technique for partial-breast irradiation similar to that used in IMPORT LOW, the volume of breast tissue irradiated with 40 Gy was shown to be associated with the occurrence of breast induration. This suggests that more conformal RT techniques could lead to fewer late AEs, as “supported by findings from the Florence accelerated partial-breast irradiation trial, which delivered 30 Gy in five fractions with a more conformal technique, although its sample size was too small to draw definitive conclusions,” according to Krug and Dunst. [Radiother Oncol 2022;177:231-235]