Younger postmenopausal patients with early-stage breast cancer may safely omit adjuvant radiotherapy following breast-conserving surgery

Adjuvant radiotherapy (RT) following breast-conserving surgery (BCS) significantly improves local control in patients with invasive BC. However, not all subgroups attain the same absolute benefit from RT, and some may safely omit RT without increasing the risk of recurrence. The IDEA trial investigated the prospect of omitting RT in younger postmenopausal patients, integrating a genomic assay into traditional selection factors to assess the feasibility of RT omission. The results demonstrated a remarkably low 5-year risk of recurrence, indicating the potential to safely forgo RT in this subgroup.

Multiple randomised trials have demonstrated that radiotherapy (RT) after breast-conserving surgery (BCS) substantially improves the local control of invasive BC. Additionally, an Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis suggests only a modest survival benefit. However, not all subgroups attain the same absolute benefit from RT, and survival benefit appears restricted to those with a larger absolute reduction in recurrence risk from RT. Multiple studies have shown a low risk of ipsilateral breast events (IBE) or other recurrences for selected patients aged 65-70 or older with stage I BC treated with BCS and endocrine therapy (ET) without adjuvant RT. Additionally, genomic assays, such as the 21-gene Oncotype DX recurrence score (RS), have been explored for patient selection. The prospective single-arm trial IDEA (Individualized Decisions for Endocrine therapy Alone), explored whether younger postmenopausal patients could also be successfully treated without RT, adding this genomic assay to classic selection factors.

Methods
The IDEA trial enrolled postmenopausal patients aged 50-69 with pT1N0 unifocal invasive BC with margins ≥2 mm after BCS whose tumours were ER+, PR+, and HER2- with Oncotype DX 21-gene recurrence score (RS) ≤18. Eligible patients could avoid RT if they consented to take at least five years of ET and study surveillance. The primary endpoint was the rate of BC recurrence at five years of follow-up after BCS.

Results

In total, 200 eligible patients were enrolled from 13 US institutions, with a. median age of 62 years; a mean 21-gene RS of 11.2 and a mean tumour size of 10 mm. The median follow-up was 5.2 years. At the 5-year landmark, overall and breast cancer-specific survival rates were both 100% among the 186 patients with clinical follow-up of at least 56 months. The 5-year freedom from any recurrence was 99%. Recurrences were minimal, with two occurring before five years and six afterwards. Among the recurrence events that occurred before five years, one was an isolated ipsilateral axillary recurrence at 21 months, and one was an IBE at 49 months. Among the recurrence events after this time, five were IBEs and one IBE plus regional recurrence. Notably, most patients (n=169) were compliant with ET. Both patients who recurred before five years were compliant, as well as three out of six who recurred later. No distant recurrences were observed. Crude rates of IBE for the entire follow-up period for patients aged 50-59 and 60-69 were 3.3% and 3.6%, respectively, while crude rates of overall relapse were 5.0% and 3.6%

Conclusions

The IDEA trial showed a very low 5-year risk of recurrence in postmenopausal women younger than 60 selected by classic clinical and biologic features combined with a genomic assay, the 21-gene Oncotype DX RS. However, long-term follow-up of this trial and others will help determine whether the option of avoiding RT can be offered to a broader group of women than what the current guidelines recommend. Notable, advances in RT have substantially reduced toxicity and short-term burden of treatment since this trial was initiated, with implications for the risk-benefit ratio of receiving RT, particularly among women with long life expectancies. Independently of these improvements, individual patient preferences and considerations may influence the decision to avoid RT.

Reference

Jagsi R, Griffith K, Harris E, et al. Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I breast cancer. Presented at SABCS 2023; Abstract GS02-08.