Article Text

Radiotherapy and tamoxifen after surgery improved local control and survival in breast cancer

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Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999 May 15; 353:1641-8.

Question

In postmenopausal women with breast cancer, does the addition of radiotherapy to 1 year of adjuvant tamoxifen after surgery reduce locoregional recurrence and improve survival?

Design

Randomised controlled trial with 10-year follow-up.

Setting

76 surgical departments in Denmark.

Patients

1460 postmenopausal women who were younger than 70 years of age and had high-risk breast cancer (node positive, tumour size > 5 cm, invasion to skin or pectoral fascia, or any combination of these characteristics). Exclusion criteria were metastatic distant disease, previous or concomitant other malignant disease, or macroscopic residual tumour. 1375 patients (94%) (median age 62 y) were included in the analysis.

Intervention

All patients had had total mastectomy and limited axillary dissection of level I and part of level II nodes. After surgery, patients were allocated to adjuvant tamoxifen, 30 mg/d for 1 year (n = 689), or radiotherapy plus tamoxifen (n = 686). Radiotherapy was directed towards the chest wall, surgical scar, and regional lymph nodes (generally 50 Gy in 25 fractions in 35 d or 48 Gy in 22 fractions in 38 d).

Main outcome measures

Overall survival, disease-free survival, and site of first recurrence (locoregional recurrence, distant metastases, or both).

Main results

At 10 years, based on Kaplan-Meier estimates, patients who received tamoxifen plus radiotherapy had greater overall and disease-free survival than patients who received tamoxifen alone (45% vs 36%, P = 0.03; and 36% vs 24%, P < 0.001, respectively). Locoregional recurrence was also reduced in the tamoxifen plus radiotherapy group (P < 0.001). Distant metastases were increased {P < 0.001}*, but the overall rate of recurrences was lower in the tamoxifen plus radiotherapy group (P < 0.001) (Table).

Conclusion

In postmenopausal women with breast cancer, the addition of radiotherapy to adjuvant tamoxifen after surgery reduced total locoregional recurrence and improved survival.

Source of funding: Not stated.

For correspondence: Dr. M. Overgaard, Department of Oncology, Aarhus University Hospital, Nørrebrogade 44, Building 5, DK-8000 Aarhus C, Denmark. FAX 45-8949-2530.

*P value calculated from data in article.

Radiotherapy plus tamoxifen vs tamoxifen alone for breast cancer at 10 years

Outcomes RT plus Tamoxifen RRR (95% CI) NNT (CI)

tamoxifen alone

All recurrences 47% 60% 22% (13 to 29) 8 (6 to 13)

Locoregional recurrence 8% 35% 78% (72 to 84) 4 (4 to 5)

with or without distant

metastases

RRI (CI) NNH (CI)

Distant metastases only 39% 25% 60% (36 to 88) 7 (5 to 10)

RT = radiotherapy. Other abbreviations defined in Glossary; RRR, RRI, NNT, NNH, and CI calculated from data in article.

Commentary

The study by Overgaard and colleagues is one of several recent studies (1, 2) that have suggested that improved locoregional control of breast cancer results in improved survival. The Early Breast Cancer Trialists' Collaborative Group (3) concluded that patients who received radiotherapy after surgery died less often from breast cancer but more frequently from other causes, often many years after receiving radiotherapy. Reassuring data from Overgaard (4) suggest no increase in non­breast cancer mortality in the Danish studies, possibly because of the way the radiotherapy was administered.

Patients in this study had only a limited axillary dissection. Women with positive nodes (one third of this group) have a greater than 40% chance of having involved nodes at level II or III (5). Many patients in the Danish study will have had residual axillary disease, and the 1 year of tamoxifen they received is suboptimal. Did inadequate local and systemic treatment in nonirradiated patients compromise survival?

Further randomised studies of high-risk postmenopausal women treated by total mastectomy and adequate axillary treatment are required before we can be certain that radiotherapy after mastectomy improves survival. Until then, patients identified as being at very high risk for local recurrence after mastectomy should have chest wall radiotherapy.

J. Michael Dixon, MBChB, MD

Royal Infirmary of Edinburgh

Edinburgh, Scotland, UK

References

1. Overgaard M, Hansen PS, Overgaard J, et al. N Engl J Med. 1997;337:949-55.

2. Ragaz J, Jackson SM, Le N, et al. N Engl J Med. 1997;337:956-62.

3. Early Breast Cancer Trialists' Collaborative Group. N Engl J Med. 1995;333: 1444-55.

4. Overgaard M. Lancet. 1999;354:866.

5. Veronesi U, Luini A, Galimberti V, et al. Eur J Surg Oncol. 1990;16:127-33.

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