Omitting Radiotherapy After Breast-Conserving Surgery in Elderly Low-Risk Patients

Radiotherapy (RT) after breast-conserving surgery (BCS) is the standard treatment for most women with early breast cancer. RT of the breast applied after BCS significantly reduces the risk for local recurrence (LR). In recent times, the incidence of LR after BCS has been steadily decreasing, due to increasing detection of smaller cancers, improved surgical techniques and effective adjuvant systemic therapy. Also, it is known that older patients with smaller, hormone receptor (HR) positive tumors have low risk for LR. Therefore, it is obvious that many patients at low risk for LR will not relapse even without RT and can be cured with surgery and endocrine therapy alone.Several studies were conducted with the goal to identify a group of patients whose risk of LR was so low that any benefit of RT would be negligible and outweighed by the risk associated with the treatment. In the Cancer and Leukemia Group B (CALGB) trial of women 70 year of age and older treated with lumpectomy and tamoxifen, the addition of RT did not change survival with over 10 years of follow-up (67% vs 66%), but significant difference in loco-regional recurrence-free survival (RFS) was seen (98% vs 90% at 10 years). Similar results were seen in recent published study of Scottish trial PRIME II . The PRIME II trial included patients age 65 years or older with small (≤ 3 cm), ER positive tumors treated with BCS and endocrine therapy and randomly assigned to RT or not. The 10-year results demonstrated a decrease in ipsilateral LR from 9,8% to 0,9% with addition of RT and no differences in overall survival (80,8% vs 80,7%).However, clinico-pathologic factors are limited in their ability to accurately predict the risk of breast cancer relapse, or the benefit from adjuvant RT. The increasing understanding of tumor biology, with the use of immunohistochemistry analysis and genomic assays enabled a better identification of patients with low-risk breast cancer. Canadian study (LUMINA trial) analyzed omission of RT after BCS in low-risk luminal A-subtype breast cancer patients. Study included women 55 years of age and older, who undergone BCS for tumor smaller than 2 cm, grade 1 or 2, luminal A- subtype. After BCS patients received only endocrine therapy without RT. After 5-year follow-up, LR was observed in 2,3% of the patients.Currently, there is a growing interest in evaluating de-escalation of RT for low-risk breast cancer patients. Ongoing clinical trials such as EXPERT, IDEA, PRECISSION, PRIMETIME, DEBRA, DBCG RT and TAILOR RT trial evaluate selective omission of adjuvant RT for low-risk early breast cancer patients based on genomic and immunohistochemistry-based biomarkers. Meanwhile, omission of RT has already become a standard option for selected cases of low-risk, ER positive breast cancers stage I, after BCS in older patients. Similar to the European recommendations, the National Comprehensive Cancer Network (NCCN) guidelines allow omission of RT in women 70 years of age and older with T1, N0, ER positive breast cancers after BCS, treated with endocrine therapy.

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