POW Journal Club

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POW Journal Club

• 21st August 2006
• Winston Woon

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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

• M Clarke,  R Collins,  S Darby,  C Davies,  et
  al. The Lancet. London Dec 17, 2005-Jan 6,
  2006.Vol.366, Iss. 9503  pg. 2087, 20 pgs

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Background

• Radiotherapy after lumpectomy confers survival
  equivalent to mastectomy
• Radiotherapy is offered routinely to patients
  postmastectomy with high risk of localregional
  relapse. (Risk factors include high grade,
  involvement of four or more nodes, dermal or
  pectoral infiltration.)
• Adjuvant radiotherapy should give local control
  rates of 95 or better at five years.

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Background

• Local recurrence
• Breast conserving surgery/RadioRx 1 to 2 per
  year
• Mastectomy recurrence usually occur within 3
  years
• (Companion series - Breast Surgery)
• Effect of local recurrence on survival is
  controversial - no longer term follow up.
• (Sarrazin 1989, Veronisi 1990, Fisher 1989, Van
  Dongen 1992, Blichert-Toft 1988. Note 6 to 10
  years follow up.)

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Hypothesis

• Local treatment affect the risk of local
  recurrence which may in turn 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.

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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

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Method
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Method

• Information was sought for every patient on her
  initial characteristics, allocated treatment and
  time to various outcomes.
• Outcomes
• Breast cancer recurrence
• Distant or isolated local recurrence
• Cause specific and overall mortality
• Incidence of second primary cancers before
  breast cancer recurrence

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Results BCS/RT

• 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, 2p0.002)
• 15-year overall mortality risks
• 35.2 vs 40.5 (reduction 5.3, SE 1.8,
  2p0.005)

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Results Mastectomy/AC

• 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, 2p0.01)
• 15-year overall mortality risks
• 42.4 vs 38.2 (increase 4.2, SE 2.7,
  2p0.0002)

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Results Mastectomy/AC

• There were 8500 women with mastectomy, axillary
  clearance,
• and Nve 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,
  2p0.0002)
• 15-year overall mortality risks
• 59.8 vs 64.2 (reduction 4.4, SE 1.2,
  2p0.0009)

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Results Mastectomy/AC
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Results Local Recurrence/Mortality

• 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 lt 10 (17 000 women), 10-20 (20 000
  women), gt20 (5000 women).

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Results Local Recurrence/Mortality
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Conclusion

• 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.
• 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.