Phase 3 Study Confirms Long-Term Efficacy of Radiation in Breast Cancer

New 10-year follow-up data from the IMPORT LOW trial (ISRCTN12852634) reinforces the safety and efficacy of partial-breast and reduced-dose whole-breast radiotherapy for women with early-stage breast cancer at below-average risk of ipsilateral breast tumor recurrence (IBTR).¹

The long-term results, published recently in The Lancet Oncology, further support the use of these tailored radiation approaches as a standard of care, potentially sparing patients from unnecessary radiation exposure while maintaining local control.

Radiotherapy is a critical component of breast cancer treatment following breast-conserving surgery, significantly reducing the risk of local recurrence. However, for a subset of patients with lower-risk disease, the absolute benefit of whole-breast irradiation can be modest, while potential adverse effects remain a concern. The IMPORT LOW trial, a randomized, open-label, multicenter, noninferiority phase 3 study, was designed to investigate whether less extensive or lower-dose radiation regimens could offer comparable efficacy with a reduced side effect profile.

The trial enrolled 2018 patients aged 50 years or older with unifocal invasive ductal adenocarcinoma (pT1–2, N0–1, grades 1–3, with microscopic margins of ≥2 mm) after breast conservation surgery. Patients were randomly assigned to 1 of 3 groups:

• Whole-breast group: 40 Gy in 15 fractions to the whole breast.
• Reduced-dose group: 36 Gy in 15 fractions to the whole breast plus 40 Gy in 15 fractions to the partial breast.
• Partial-breast group: 40 Gy in 15 fractions to the partial breast only.

The median follow-up for all groups was approximately 120 months (10 years).

Key Findings: Comparable Efficacy and Low Adverse Events

The 10-year outcomes demonstrated a consistently low cumulative incidence of IBTR across all 3 treatment arms:

• Whole-breast group: 2.8% (n = 17/674)
• Reduced-dose group: 1.9% (n = 1/673)
• Partial-breast group: 3.0% (n = 17/669)

The estimated absolute difference in 10-year IBTR incidence, when comparing the experimental groups with the whole-breast group, was –1.02% (95% CI, –1.98 to 0.99) for the reduced-dose group and 0.16% (95% CI, –1.28 to 2.89) for the partial-breast group. These findings affirm the noninferiority of both reduced-dose and partial-breast radiotherapy, indicating that these approaches offer comparable long-term local control to traditional whole-breast irradiation.

Beyond IBTR, the study also assessed other important outcomes:

• Locoregional recurrence: Occurred in 3.2% of the whole-breast group, 1.9% of the reduced-dose group, and 3.5% of the partial-breast group.
• Distant recurrence-free survival: At 10 years, this was 86.9% in the whole-breast group, 85.9% in the reduced-dose group, and 89.8% in the partial-breast group.
• Overall survival: 10-year all-cause mortality was 12.3% in the whole-breast group, 13.1% in the reduced-dose group, and 9.8% in the partial-breast group.

Clinician-reported late adverse effects remained low and similar across all 3 groups. Breast shrinkage was the most common adverse effect, reported in 9% of the whole-breast group, 9% of the reduced-dose group, and 7% of the partial-breast group. The trial's initial 5-year results had previously indicated fewer patient-reported adverse effects with partial-breast radiotherapy, though patient-reported outcomes were not collected for the 10-year analysis.

Implications for Clinical Practice

The 10-year data from the IMPORT LOW trial provides robust, long-term evidence that partial-breast radiotherapy and reduced-dose whole-breast radiotherapy are as safe and effective as standard whole-breast radiotherapy for carefully selected patients with low-risk early breast cancer. This reinforces previous 5-year findings that have already influenced major clinical guidelines globally, including those from the UK National Institute for Health and Care Excellence (NICE) in 2018, the European Society of Radiation Oncology (ESTRO) in 2022, and the American Society of Radiation Oncology (ASTRO) in 2023.

The trial utilized a simple tangential external beam radiation technique for partial-breast irradiation, which is relatively straightforward to implement in clinical settings, requiring minimal additional training or resources. This practical advantage further supports its widespread adoption.

"The long-term results of this study confirm that a less aggressive approach—limiting radiotherapy to the part of the breast where the [tumor] was—is just as effective as traditional whole-breast radiotherapy. Patients receiving partial breast radiotherapy experience fewer side effects while maintaining excellent cancer control. This approach has now been widely adopted across the UK and internationally, significantly reducing the treatment burden while delivering the same long-term success,” said Dr Anna Kirby, first author of the study, consultant clinic oncologist at The Royal Marsden NHS Foundation Trust, and reader in breast cancer radiotherapy at The Institute of Cancer Research, in a press release.²

While the study's design was not powered to detect differences in rare long-term toxicities such as cardiac disease or secondary malignancies, the reduced radiation doses to organs at risk like the lung and heart with partial-breast radiotherapy suggest a potential for even lower risks of these events over a patient's lifetime compared to whole-breast radiotherapy.

REFERENCES:

1. Kirby AM, Finneran L, Griffin CL, et al. Partial-breast radiotherapy after breast conservation surgery for women with early breast cancer (UK IMPORT LOW): 10-year outcomes from a multicentre, open-label, randomised, controlled, phase 3, non-inferiority trial. Lancet Oncol. 2025 Jul;26(7):898-910. doi: 10.1016/S1470-2045(25)00194-9. Epub 2025 Jun 11.

2. Targeted radiotherapy just as effective for low-risk breast cancer and reduces risk of side effects. News Release. The Institute of Cancer Research. July 15, 2025. Accessed July 15, 2025. https://tinyurl.com/2eds7upu