Five-year results from the prospective TOP-1 study (BOOG 2016-01), presented by Lotte Bouwman at ESMO 2026 during the Rapid Oral Session, showed that omitting adjuvant radiotherapy after breast-conserving surgery in older women with low-risk, estrogen receptor-positive (ER+) breast cancer who did not receive endocrine therapy was associated with a 14.8% local recurrence rate at five years.
Although breast cancer-specific survival remained excellent and most local recurrences could be managed with repeat breast-conserving surgery, the recurrence rate was substantially higher than anticipated.
Background
Adjuvant radiotherapy following breast-conserving surgery is an established treatment for patients with early-stage breast cancer. However, previous studies have investigated whether radiotherapy can be safely omitted in selected older patients with favorable tumor characteristics.
Importantly, most previous radiotherapy omission trials included patients receiving adjuvant endocrine therapy, which also reduces the risk of local recurrence.
According to Dutch recommendations, endocrine therapy is not routinely advised for patients with small, low-grade T1 breast cancers.
The TOP-1 study was designed to evaluate the safety of omitting radiotherapy in older women who were also not receiving endocrine therapy, addressing an important question about treatment de-escalation in this population.
Study Design and Patient Population
TOP-1 was a prospective, multicenter, observational, single-arm study involving women aged 70 years or older with low-risk, ER-positive, HER2-negative early-stage breast cancer who underwent breast-conserving surgery without subsequent radiotherapy or endocrine therapy.
Eligible tumors were required to meet the following criteria:
- ER expression ≥50% and HER2-negative status.
- Tumor size ≤1 cm with grade 1 or 2 histology, or ≤2 cm with grade 1 histology.
- Negative surgical margins.
The primary endpoint was five-year local recurrence, defined as a histologically confirmed invasive ipsilateral breast cancer event. Secondary endpoints included contralateral breast cancer, overall survival, and breast cancer-specific survival.
Between January 2017 and September 2021, 792 patients were enrolled, with a median age of 73.6 years.
Median follow-up was 5.1 years.
Five-Year Local Recurrence Results
At five years, 123 patients had developed a local recurrence, corresponding to a cumulative incidence of 14.8% (95% CI, 12.3–17.5).
This was considerably higher than the recurrence estimates used when designing the trial. The investigators had anticipated a five-year recurrence risk below 7.5% without radiotherapy, based on registry data reporting a 1.3% recurrence risk among patients receiving radiotherapy.
The observed rate also exceeded the 10% recurrence threshold considered acceptable during the study’s planning. These findings suggest that omission of both radiotherapy and endocrine therapy carries a meaningful risk of local recurrence, even in older patients with small, favorable-risk tumors.
Management of Local Recurrences
Despite the increased recurrence rate, most patients who developed local recurrence were able to undergo further surgical treatment.
Among the 123 patients with local recurrence:
- 114 patients (92.7%) underwent surgery.
- 86 of those undergoing surgery (75.4%) received repeat breast-conserving surgery.
- 70 patients (56.7%) received radiotherapy.
- 43 patients (35.0%) received endocrine therapy.
These findings indicate that many recurrences remained amenable to breast-preserving treatment, although additional surgery and other therapies were required.
Survival and Contralateral Breast Cancer
Contralateral breast cancer was diagnosed in 32 patients (4.0%) during follow-up. Overall, 81 patients (10.2%) died, with only two deaths attributed to breast cancer. Despite the relatively high incidence of local recurrence, breast cancer-specific survival remained excellent at five years.
However, longer follow-up is needed to determine whether the increased recurrence risk affects subsequent treatment burden, long-term quality of life, or survival outcomes.
Clinical Implications
The TOP-1 results raise important questions about the omission of adjuvant treatment in older women with low-risk ER-positive breast cancer.
While previous trials have supported radiotherapy omission in selected older patients receiving endocrine therapy, TOP-1 examined a different population in which both radiotherapy and endocrine therapy were omitted.
The five-year local recurrence rate of 14.8% suggests that favorable tumor biology and older age alone may not provide sufficient protection against local recurrence.
Nevertheless, the excellent breast cancer-specific survival and the possibility of successful salvage treatment suggest that radiotherapy omission may remain an option for carefully selected patients.
Treatment decisions should consider individual preferences, comorbidities, life expectancy, potential radiotherapy toxicity, and the patient’s willingness to accept a higher risk of local recurrence.
As TOP-1 was a single-arm observational study, it cannot directly establish the comparative benefit of radiotherapy or endocrine therapy.
Conclusion
The TOP-1 study demonstrated a 14.8% five-year local recurrence risk following breast-conserving surgery without adjuvant radiotherapy or endocrine therapy in women aged 70 years or older with low-risk ER-positive breast cancer.
Although the recurrence rate exceeded expectations, most recurrences were managed surgically, and breast cancer-specific survival remained excellent.
The findings emphasize that omitting both radiotherapy and endocrine therapy involves a clinically important trade-off between reducing treatment burden and increasing local recurrence risk.
Individualized decision-making and longer-term follow-up remain essential when considering treatment de-escalation in this population.
