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Early Breast Cancer Trialists’ Collaborative Group (EBCTCG)

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials . EBCTCG Lancet 2005; 366: 2087-2106. Background .

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Early Breast Cancer Trialists’ Collaborative Group (EBCTCG)

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  1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials EBCTCG Lancet 2005; 366: 2087-2106

  2. Background • In early breast cancer, variations in local treatment that • substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. • To examine this relationship, collaborative meta-analyses • were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995.

  3. Data available Information was available on 42 000 women in 78 randomised treatment comparisons: • radiotherapy vs no radiotherapy, 23 500 • more vs less surgery, 9300 • more surgery vs radiotherapy, 9300

  4. Availability of data from unconfounded randomised trials of local therapy that began by 1995

  5. Breast-conserving surgery (BCS) There were 7300 women with BCS in trials of  RT RT was generally just to the conserved breast 5-year local recurrence risks (mainly in the conserved breast): • 7% vs 26% (reduction 19%) 15-year breast cancer mortality risks: • 30.5% vs 35.9% (reduction 5.4%, SE 1.7, 2p=0.002) 15-year overall mortality risks: • 35.2% vs 40.5% (reduction 5.3%, SE 1.8, 2p=0.005)

  6. Effect of radiotherapy after breast-conserving surgery (10 trials of BCS  RT) on local recurrence

  7. Effect of radiotherapy after breast-conserving surgery (10 trials of BCS  RT) on breast cancer mortality

  8. Effect of radiotherapy after breast-conserving surgery (10 trials of BCS  RT) on local recurrence and on breast cancer mortality 6097 women with node-negative disease

  9. Effect of radiotherapy after breast-conserving surgery (10 trials of BCS  RT) on local recurrence and on breast cancer mortality 1214 women with node-positive disease

  10. Mastectomy and axillary clearance: N-ve There were 1400 women with mastectomy, axillary clearance, and N-ve disease in trials of RT RT was generally to the chest wall and regional lymph nodes 5-year local recurrence risks: • 2% vs 6% (reduction 4%) 15-year breast cancer mortality risks: • 31.3% vs 27.7% (increase 3.6%, SE 3.6, 2p=0.01) 15-year overall mortality risks: • 42.4% vs 38.2% (increase 4.2%, SE 2.7, 2p=0.0002)

  11. Mastectomy and axillary clearance: N+ve There were 8500 women with mastectomy, axillary clearance, and N+ve disease in trials of RT RT was generally to the chest wall and regional lymph nodes 5-year local recurrence risks: • 6% vs 23% (reduction 17%) 15-year breast cancer mortality risks: • 54.7% vs 60.1% (reduction 5.4%, SE 1.3, 2p=0.0002) 15-year overall mortality risks: • 59.8% vs 64.2% (reduction 4.4%, SE 1.2, 2p=0.0009)

  12. Effect of radiotherapy after mastectomy and axillary clearance (25 trials of Mast+AC  RT) on local recurrence and on breast cancer mortality1428 women with node-negative disease

  13. Effect of radiotherapy after mastectomy and axillary clearance (25 trials of Mast+AC  RT) on local recurrence and on breast cancer mortality8505 women with node-positive disease

  14. About three-quarters of the eventual local recurrence risk occurred during the first 5 years. To help relate the effect on local recurrence to that on breast cancer mortality, the 24 types of local treatment comparison were grouped according to whether or not the 5-year local recurrence risk was < 10% (17 000 women), 10-20% (20 000 women), >20% (5000 women). Methods

  15. Absolute reduction in 5-year local recurrence risk: 78 trials grouped into 24 types of local treatment comparison, based on treatments compared and nodal status

  16. Breast cancer mortality risks by time since randomisation and by category of absolute reduction in 5-year local recurrence risk (a) 16 804 women, 43% N+ve, (b+c) 25 276 women, 51% N+ve

  17. Local recurrence and breast cancer mortality for 12 treatment comparisons that produce <10% absolute reduction in 5-year local recurrence risk16 804 women, 43% with node-positive disease

  18. Local recurrence and breast cancer mortality for 12 treatment comparisons that produce >10% absolute reduction in 5-year local recurrence risk25 276 women, 51% with node-positive disease

  19. Proportional and absolute reductions produced by radiotherapy Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of RT (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large.

  20. Effects of age and tumour characteristics on 5-year risks of local recurrence in trials of radiotherapy (a) after breast-conserving surgery in women with node-negative disease (BCS±RT) and (b) after mastectomy and axillary clearance in women with node-positive disease (Mast+AC±RT)

  21. Radiotherapy side-effects • Trials of RT were combined with those of RT vs more surgery. • There was an excess incidence of contralateral breast cancer (rate ratio 1.18, SE 0.06, 2p=0.002). • There was also an excess of non-breast-cancer mortality (rate ratio 1.12, SE 0.04, 2p=0.001), heart disease (rate ratio 1.27, SE 0.07, 2p=0.0001) and lung cancer (rate ratio 1.78, SE 0.22, 2p=0.0004). • Both excesses were slight during the first 5 years, but continued after year 15.

  22. Effect of radiotherapy on contralateral breast cancer incidence and on non-breast-cancer mortality (46 trials of adding radiotherapy, and 17 trials of radiotherapy vs more surgery) (29 623 women)

  23. Effect of radiotherapy on incidence of second cancers before recurrence of breast cancer(23 500 women in 46 trials of adding radiotherapy, and 9300 in 17 trials of radiotherapy vs more surgery)

  24. Effect of radiotherapy on mortality from causes other than breast cancer (23 500 women in 46 trials of adding radiotherapy, and 9300 in 17 trials of radiotherapy vs more surgery)

  25. Interpretation In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

  26. Effect of radiotherapy on breast cancer mortality and on all-cause mortality after breast-conserving surgery (BCSRT)7311 women (17% with node-positive disease)

  27. Effect of radiotherapy on breast cancer mortality and on all-cause mortality after mastectomy with axillary clearance (Mast+ACRT)8505 women with node-positive disease

  28. Conclusions (1) In early breast cancer, local treatments that substantially improve local control have little effect on breast cancer mortality during the first few years, but have definite, although moderate, effects by 15 years, and avoidance of local recurrence in a conserved breast and elsewhere are of comparable relevance to 15-year breast cancer mortality.

  29. Conclusions (2) These trials of radiotherapy and of the extent of surgery show that, in the hypothetical absence of other causes of death, about one breast cancer death over the next 15 years would be avoided for every four local recurrences avoided. Although the management of early breast cancer continues to change, it is reasonable to assume that this approximate four-to-one relationship will continue to apply and will still be of relevance to future treatment choices.

  30. Conclusions (3) The evidence as to what will happen after year 15 is still limited. Longer follow-up will help assess the additional benefits and risks after year 15.

  31. Webfigures

  32. Radiotherapy after breast-conserving surgery, generally with axillary clearance (BCSRT) in all women(node-negative or node-positive)(7311 women, 17% with node-positive disease)

  33. Radiotherapy after breast-conserving surgery, generally with axillary clearance (BCSRT) in women with node-negative disease (6097 women)

  34. Radiotherapy after breast-conserving surgery, generally with axillary clearance (BCSRT) in women with node-positive disease(1214 women)

  35. Radiotherapy after mastectomy with axillary clearance (Mast+ACRT) in all women (9933 women, 86% with node-positive disease)

  36. Radiotherapy after mastectomy with axillary clearance (Mast+ACRT) in women with node-negative disease(1428 women)

  37. Radiotherapy after mastectomy with axillary clearance (Mast+ACRT) in all women with node-positive disease (8505 women, many with the actual number of involved nodes unknown)

  38. Radiotherapy after mastectomy with axillary clearance (Mast+ACRT) in women with 1-3 involved lymph nodes (pN1-3)(1890 women)

  39. Radiotherapy after mastectomy with axillary clearance (Mast+ACRT) in women with 4 or more involved lymph nodes (pN4+) (1868 women)

  40. 12 types of treatment comparison that yield <10% isolated local recurrence risk reduction (16 804 women, 43% with node-positive disease)

  41. 12 types of treatment comparison that yield >10% isolated local recurrence risk reduction (25 276 women, 51% with node-positive disease)

  42. Breast cancer mortality rate ratio by time since randomisation and by category of absolute reduction in 5-year local recurrence risk

  43. Homogeneity of 24 breast cancer mortality rate ratios, given the category (<10%, 10-20%, or >20%) of absolute reduction in 5-year local recurrence risk

  44. Radiotherapy after breast conserving surgery in node-negative disease Isolated local recurrence Breast cancer mortality Any death

  45. Radiotherapy after mastectomy and axillary clearance in node-positive disease Isolated local recurrence Breast cancer mortality Any death

  46. 12 types of treatment comparison that yield >10% isolated local recurrence risk reduction Isolated local recurrence Breast cancer mortality Any death

  47. Effect of radiotherapy on contralateral breast cancer incidence and on non-breast-cancer mortality (46 trials of adding radiotherapy, and 17 trials of radiotherapy vs more surgery) (29 623 women)

  48. Radiotherapy versus not, in women with node-negative disease Isolated local recurrence Breast cancer mortality Any death

  49. Radiotherapy versus not, in women with node-positive disease Isolated local recurrence Breast cancer mortality Any death

  50. ‘More’ surgery versus ‘less’ surgery, in women with node-negative disease Isolated local recurrence Breast cancer mortality Any death

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