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Multiple randomized trials have established adjuvant endocrine therapy (ET) and whole breast irradiation (WBI) as the standard approach after breast conserving surgery (BCS) in early stage breast cancer. The omission of WBI has likewise been studied in multiple trials and resulted in reduced local control with maintained survival rates and has therefore been adapted as a treatment option in selected patients in several guidelines. Omitting ET instead of WBI might also be a valuable option as both treatments have distinctly different side effect profiles. However the clinical outcomes of  BCS+ET vs. BCS+WBI have not been thoroughly analyzed.

We performed a systematic literature review searching for randomized trials comparing BCS+ET vs. BCS+WBI in low risk breast cancer patients with publication dates after 2000. We excluded trials using any form of chemotherapy, regional nodal radiation and mastectomy. The meta-analysis was performed using a two step process. First, the published individual patient EBCTCG data (IPD) were used to allow a direct and indirect comparison for overall survival (OS) and breast cancer-specific survival (BCSS). Second, we extracted all available published event rates and the effect-sizes for OS, BCSS, local- (LR) and regional recurrences (RR), recurrence-free interval (RFI), disease-free survival (DFS), distant metastases-free interval (DMFI), contralateral breast cancer (CBC), second cancer other than breast cancer (SCNBC) and mastectomy-free interval (MFI) as investigated endpoints and compared them in a network meta-analysis. Statistical analysis was performed using the Microsoft Excel add-in MetaXL 5.3 utilizing the inverse variance heterogeneity model.

We identified three studies including a direct a comparison of BCS+ET vs. BCS+WBI (n=1059) and nine studies randomizing overall 5786 patients additionally to BCS only and BCS+WBI+ET resulting in 4 arms. Using IPD OS and BCSS were not significantly different between BCS+ET and BCS+WBI after 10 years (OR=0.85; CI95%:0.59-1.22; p=0.369) and (OR=0.72; CI95%:0.38-1.36; p=0.305). In the network-analysis LR was significantly lower in the BCS+WBI group in comparison to the BCS+ET group (HR=0.62; CI95%:0.42-0.92; p=0.019).RR, RFI and DFS were not different between the two approaches. We also did not find any differences in OS (HR=1.00; CI95%:0.63-1.59; p=0.984) and BCSS (OR=1.18; CI95%:0.28-4.97; p=0.823). Further, we found a lower DMFI, a higher rate of CBC and a reduced MFI in the BCS+WBI-arm.

Evidence from direct and indirect comparison suggests that BCS+WBI without ET might be an equivalent de-escalation strategy to BCS+ET in low risk breast cancer. Adverse event rates and quality of life measures have to be further compared between these approaches.