Background
Phase III RCT (CALGB 9343). 636 women aged ≥70 years with clinical stage T1 (≤2 cm) N0, ER+ breast cancer treated with breast-conserving surgery and margins negative for invasive cancer. All patients received tamoxifen. Randomized to whole breast irradiation (WBI) vs no RT. This report is the 10-year outcomes analysis.
Interventions and follow up
Arm A: Tamoxifen 20 mg/day × 5 years + whole breast RT (45 Gy/25 fx + optional 14 Gy boost)
Arm B: Tamoxifen 20 mg/day × 5 years alone (no RT)
Primary endpoint: Time to local or regional recurrence
mFollow up: Median 12.6 year
Arm B: Tamoxifen 20 mg/day × 5 years alone (no RT)
Primary endpoint: Time to local or regional recurrence
mFollow up: Median 12.6 year
Results
10-year locoregional recurrence: 2% (tamoxifen+RT) vs 9% (tamoxifen alone), P<.001
10-year mastectomy rate: 4% vs 9% (RT vs no RT)
10-year DFS: 77% vs 79%, P=.41 — not significant
10-year OS: 67% vs 66%, P=.80 — not significant
10-year distant metastasis-free survival: No significant difference
10-year mastectomy rate: 4% vs 9% (RT vs no RT)
10-year DFS: 77% vs 79%, P=.41 — not significant
10-year OS: 67% vs 66%, P=.80 — not significant
10-year distant metastasis-free survival: No significant difference
Adverse events
Main adverse events: RT was well tolerated. Competing mortality was high in this elderly cohort (most deaths not from breast cancer). Tamoxifen toxicities: thromboembolic events and endometrial cancer risk as expected. No excess cardiac toxicity with RT.
Conclusions
Among women ≥70 with T1 ER+ breast cancer on tamoxifen, the absolute benefit of RT was a 7% reduction in locoregional recurrence at 10 years but with no improvement in DFS, distant disease-free survival, or OS. These data support omission of radiation in this population after shared decision-making.
Key Limitations
Key Limitations: Restricted to women ≥70 with small (T1), ER+, N0 tumors — not applicable to younger, node-positive, or ER− patients. 7% absolute reduction in LR is not trivial for all patients. Tamoxifen compliance was not tracked rigorously. Contemporary aromatase inhibitors (used in current practice) may further reduce LR risk, potentially widening the margin for RT omission. OS in this trial was driven by competing non-cancer mortality, limiting conclusions about breast cancer death prevention.
Clinical Context
CALGB 9343 and PRIME II are the two pivotal RCTs supporting RT omission in elderly low-risk breast cancer. ASTRO guidelines now support omission of RT in women ≥70 with T1N0 ER+ tumors receiving adjuvant endocrine therapy after BCS, based primarily on these data. This approach is endorsed in NCCN guidelines as an acceptable alternative following shared decision-making.
References