乳がん放射線治療の効果は10年続く(Breast cancer radiotherapy benefits last a decade)

2024-08-09

2024-08-08 エディンバラ大学

スコットランドでの30年間にわたる研究で、早期乳がん患者に対する手術後の放射線療法が、10年間にわたるがんの再発防止に効果があることが確認された。しかし、放射線療法を受けた群と受けなかった群の長期的な生存率には大きな差がなかった。放射線療法を受けた群では乳がんによる死亡率が低かったものの、他のがんによる死亡率が高かった。これらの結果は、早期乳がん治療における放射線療法の長期的なリスクと利益を評価する重要性を示している。

<関連情報>

早期手術可能乳癌女性における術後放射線療法(Scottish Breast Conservation Trial): 無作為化比較第3相試験の30年アップデート Postoperative radiotherapy in women with early operable breast cancer (Scottish Breast Conservation Trial): 30-year update of a randomised, controlled, phase 3 trial

Linda J Williams, PhD ;Prof Ian H Kunkler, FRCR;Karen J Taylor, PhD;Joanna Dunlop, PhD;Tammy Piper, MSc;Jacqueline Caldwell, MBA;et al.
The Lancet Oncology Published:August 07, 2024
DOI:https://doi.org/10.1016/S1470-2045(24)00347-4

Summary

Background
Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial.

Methods
In this randomised, controlled, phase 3 trial across 14 hospitals in Scotland, women aged younger than 70 years with early breast cancer (tumours ≤4 cm [T1 or T2 and N0 or N1]) were included. They underwent breast-conserving surgery (1 cm margin) with axillary node sampling or clearance. Oestrogen receptor (ER)-rich patients (≥20 fmol/mg protein) received 20 mg oral tamoxifen daily for 5 years. ER-poor patients (<20 fmol/mg protein) received chemotherapy (cyclophosphamide 600 mg/m², methotrexate 50 mg/m², and fluorouracil 600 mg/m² every 21 days intravenously in eight courses). Stratification was by menstrual status (within or more than 12 months from last menstrual period) and ER status (oestrogen concentration ≥20 fmol/mg protein, <20 fmol/mg protein, or unknown) and patients were randomly assigned (1:1) to high-dose (50 Gy in 20–25 fractions) local or locoregional radiotherapy versus no radiotherapy. No blinding was possible due to the nature of the treatment. We report the primary endpoint of the original trial, ipsilateral breast tumour recurrence, and the co-primary endpoint, overall survival. Clinical outcomes were compared by the log-rank test. Hazard ratios (HRs) are reported, with no radiotherapy as the reference group. Failures of the proportional hazards assumption are reported if significant. All analyses are by intention to treat.

Findings
Between April 1, 1985, and Oct 2, 1991, 589 patients were enrolled and randomly assigned to the two treatment groups (293 to radiotherapy and 296 to no radiotherapy). After exclusion of four ineligible patients (two in each group), there were 291 patients in the radiotherapy group and 294 patients in the no radiotherapy group. Median follow-up was 17·5 years (IQR 8·4–27·9). Ipsilateral breast tumour recurrence was significantly lower in the radiotherapy group than in the no radiotherapy group (46 [16%] of 291 vs 107 [36%] of 294; HR 0·39 [95% CI 0·28–0·55], p<0·0001). Although there were differences in the hazard rate for ipsilateral breast tumour recurrence in the first decade after treatment (HR 0·24 [95% CI 0·15–0·38], p<0·0001), subsequent risks of ipsilateral breast tumour recurrence were similar in both groups (0·98 [0·54–1·79], p=0·95). There was no difference in overall survival between the two groups (median 18·7 years [95% CI 16·5–21·5] in the no radiotherapy group vs 19·2 years [16·9–21·3] in the radiotherapy group; HR 1·08 [95% CI 0·89–1 ·30], log-rank p=0·43).

Interpretation
Our findings suggest that patients whose biology predicts a late relapse a decade or more after breast-conserving surgery for early breast cancer might gain little from adjuvant radiotherapy.

Funding
Breast Cancer Institute (part of Edinburgh and Lothian Health Foundation) and PFS Genomics (now part of Exact Sciences).