Ten-year follow-up data from the phase 3 UK IMPORT LOW trial demonstrates that partial-breast and reduced-dose radiotherapy continue to provide equivalent outcomes to whole-breast radiotherapy in patients with low-risk early breast cancer, according to results published in The Lancet Oncology.
The multicenter, open-label trial randomly assigned 2,018 patients between May 2007 and October 2010 to receive one of three radiation regimens: whole-breast radiation at 40 Gy in 15 fractions (n=675), reduced-dose radiation at 36 Gy in 15 fractions to the whole breast plus 40 Gy in 15 fractions to the partial breast (n=674), or partial-breast radiation at 40 Gy in 15 fractions (n=669).
Long-Term Efficacy Outcomes
At 10 years, the cumulative incidence of ipsilateral breast tumor recurrence (IBTR) remained low across all treatment groups. The whole-breast radiation group experienced a 2.8% IBTR rate (95% CI, 1.8%-4.5%), compared to 1.9% (95% CI, 1.1%-3.5%) in the reduced-dose group and 3.0% (95% CI, 1.9%-4.8%) in the partial-breast radiation group.
The estimated absolute differences in 10-year IBTR incidence compared to whole-breast radiation were -1.02% (95% CI, -1.98% to 0.99%) for reduced-dose radiation and 0.16% (95% CI, -1.28% to 2.89%) for partial-breast radiation, confirming non-inferiority.
Locoregional recurrence rates at 10 years were 3.2% (95% CI, 2.0%-5.0%) for whole-breast radiation, 1.9% (95% CI, 2.0%-3.5%) for reduced-dose radiation, and 3.5% (95% CI, 2.3%-5.4%) for partial-breast radiation. Distant recurrence rates were similarly low across groups at approximately 3.8-4.1%.
Safety Profile and Adverse Events
The long-term safety profile remained favorable across all treatment arms. Ten-year all-cause mortality rates were 12.3% (95% CI, 10.0%-15.1%) in the whole-breast group, 13.1% (95% CI, 10.7%-15.9%) in the reduced-dose group, and 9.8% (95% CI, 7.7%-12.4%) in the partial-breast group.
Late adverse events were infrequent, with breast shrinkage being the most common, occurring in 9% of both the whole-breast and reduced-dose groups, and 7% of the partial-breast group. Other late effects included rib fractures in 4, 7, and 3 patients respectively; symptomatic lung fibrosis in 4, 6, and 4 patients; and ischemic heart disease in 7, 5, and 5 patients across the three groups.
Patient Population and Study Design
The trial enrolled patients aged 50 years and older with invasive adenocarcinoma measuring 3 cm or smaller in diameter, unifocal disease, grades 1-3 disease, and negative axillary lymph nodes or 1-3 positive nodes. The median patient age was 63 years (IQR, 58-68), with most patients having grade 2 tumors (48%). Median follow-up ranged from 120-121 months across the three treatment groups.
Clinical Implications
"This prespecified 10-year analysis of IBTR and clinician-reported adverse effects in patients with a lower-than-average risk of IBTR reaffirms that partial-breast and reduced-dose radiotherapy are as effective and safe as whole-breast radiotherapy in this population," wrote lead study author Anna M. Kirby, FRCR, from the Breast Unit at Royal Marsden NHS Foundation Trust and Institute of Cancer Research.
The researchers emphasized that the 10-year incidence of IBTR was no higher than 3%, and clinician-reported moderate-marked breast shrinkage occurred in less than 10% of patients in all groups. They noted that demonstration of long-term efficacy despite reduction in the irradiated volume of breast tissue supports the ongoing use of partial-breast radiotherapy delivered by intensity-modulated radiation techniques as standard of care internationally.
Second primary cancers apart from breast tumors were reported in 9% of the whole-breast radiation group, 8% of the reduced-dose radiation group, and 6% of the partial-breast radiation group, with lung, colorectal, and gynecological cancers being the most common types.
