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Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus)

  1. Jenna Morgan1,*,
  2. Lynda Wyld1,
  3. Karen A Collins2,
  4. Malcolm W Reed1

Editorial Group: Cochrane Breast Cancer Group

Published Online: 16 MAY 2014

Assessed as up-to-date: 27 MAR 2013

DOI: 10.1002/14651858.CD004272.pub3


How to Cite

Morgan J, Wyld L, Collins KA, Reed MW. Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus). Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD004272. DOI: 10.1002/14651858.CD004272.pub3.

Author Information

  1. 1

    The University of Sheffield, Academic Unit of Surgical Oncology, Department of Oncology, Sheffield, South Yorkshire, UK

  2. 2

    Sheffield Hallam University, Centre for Health and Social Care Research, Sheffield, UK

*Jenna Morgan, Academic Unit of Surgical Oncology, Department of Oncology, The University of Sheffield, Sheffield, South Yorkshire, S10 2RX, UK. jenna.morgan@doctors.org.uk.

Publication History

  1. Publication Status: Stable (no update expected for reasons given in 'What's new')
  2. Published Online: 16 MAY 2014

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Characteristics of included studies [ordered by study ID]
CRC

MethodsRandomised controlled trial


ParticipantsWomen (aged 70+) with operable breast cancer


InterventionsSurgery plus tamoxifen (40 mg/d) versus tamoxifen alone


OutcomesSurvival - overall; Disease-free survival; Local disease control; Distant metastasis-free survival; Quality of life


NotesComparability between groups at the baseline: stated as "good"


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random numbers

Allocation concealment (selection bias)Low riskCentral randomisation.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding of these studies was not possible due to interventions used, therefore this has not been assessed.

Incomplete outcome data (attrition bias)
All outcomes
Low riskInclusion of all randomised participants in the analysis - 16 protocol violators (full explanations) analysed as randomised (intention-to-treat)

Selective reporting (reporting bias)Low riskSufficient data reported on all relevant outcomes.

EORTC 10851

MethodsRandomised controlled trial


ParticipantsWomen (aged 70+) with operable breast cancer


InterventionsSurgery versus tamoxifen (20 mg/d)


OutcomesSurvival - overall; Disease-free survival; Local disease control; Distant metastasis free survival


NotesComparability between groups at the baseline: stated as "well-balanced"


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot stated (but stated that it was randomised).

Allocation concealment (selection bias)Low riskCentral randomisation.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding of these studies was not possible due to interventions used, therefore this has not been assessed.

Incomplete outcome data (attrition bias)
All outcomes
Low riskInclusion of all randomised participants in the analysis: analysis based on intention-to-treat. 13 found ineligible after randomisation and excluded from analysis. 1 participant allocated tamoxifen opted for surgery.

Selective reporting (reporting bias)Low riskSufficient data reported on all relevant outcomes.

GRETA

MethodsRandomised controlled trial


ParticipantsWomen (aged 70+) with operable breast cancer


InterventionsSurgery plus tamoxifen (20 mg/d) versus tamoxifen alone


OutcomesSurvival - overall; Disease-free survival; Local disease control; Distant metastasis free survival


NotesComparability between groups at the baseline: good


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number

Allocation concealment (selection bias)Low riskCentral randomisation.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding of these studies was not possible due to interventions used, therefore this has not been assessed

Incomplete outcome data (attrition bias)
All outcomes
Low riskInclusion of all randomised participants in the analysis: intention-to-treat analysis

Selective reporting (reporting bias)Low riskSufficient data reported on all relevant outcomes

Naples

MethodsRandomised controlled trial


ParticipantsWomen (aged 70+) with operable breast cancer


InterventionsSurgery plus tamoxifen (20 mg/d) versus tamoxifen alone


OutcomesSurvival - overall; Disease-free survival


NotesNo data


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskUnclear

Allocation concealment (selection bias)Unclear riskUnclear

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding of these studies was not possible due to interventions used, therefore this has not been assessed

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants included in results presented.

Selective reporting (reporting bias)Unclear riskAdequate outcomes reported on but insufficient data presented for meta-analysis

Nottingham 1

MethodsRandomised controlled trial


ParticipantsWomen (aged 70+) with operable breast cancer


InterventionsSurgery versus tamoxifen (40 mg/d)


OutcomesSurvival - overall; Disease-free survival; Local disease control; Distant metastasis-free survival


NotesComparability between groups at the baseline: appears similar by age, tumour volume and tumour site. Little else specified


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom card allocation

Allocation concealment (selection bias)Unclear riskNot stated

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding of these studies was not possible due to interventions used, therefore this has not been assessed

Incomplete outcome data (attrition bias)
All outcomes
Low riskInclusion of all randomised participants in the analysis: analysis based on intention-to-treat. 2 incorrect randomisations in each group. 122/135 followed up. Other 13 participants assessed by GP at time of analysis as too frail to attend clinic

Selective reporting (reporting bias)Low riskSufficient data reported on all relevant outcomes

Nottingham 2

MethodsRandomised controlled trial


ParticipantsWomen (aged 70+) with operable breast cancer


InterventionsSurgery plus tamoxifen versus tamoxifen (20 mg/d)


OutcomesSurvival - overall; Disease-free survival


NotesComparability between groups at the baseline: stated as "similarly matched for age" (no other characteristics reported)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot stated

Allocation concealment (selection bias)Unclear riskNot stated

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding of these studies was not possible due to interventions used, therefore this has not been assessed

Incomplete outcome data (attrition bias)
All outcomes
Low riskInclusion of all randomised participants in the analysis: analysed as randomised (intention-to-treat)

Selective reporting (reporting bias)Low riskSufficient data reported on all relevant outcomes

St Georges

MethodsRandomised controlled trial


ParticipantsWomen (aged 70+) with operable breast cancer


InterventionsSurgery versus tamoxifen (20 mg/d)


OutcomesSurvival - overall; Disease-free survival; Local disease control; Distant metastasis free survival


NotesComparability between groups at the baseline: More T4 tumours in primary endocrine therapy group (n = 14/100 versus n = 7/100 in the surgery group) but, with small numbers in each arm, this may not be significant. Ages were similar. No other characteristics were reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot stated

Allocation concealment (selection bias)Unclear riskNot stated

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding of these studies was not possible due to interventions used, therefore this has not been assessed

Incomplete outcome data (attrition bias)
All outcomes
Low riskInclusion of all randomised participants in the analysis: no errors or exclusions were reported

Selective reporting (reporting bias)Low riskSufficient data reported on all relevant outcomes

 
Comparison 1. Surgery versus primary endocrine therapy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Survival - overall3495Hazard Ratio (95% CI)0.98 [0.81, 1.20]

 
Comparison 2. Surgery plus endocrine therapy versus primary endocrine therapy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Survival - overall31076Hazard Ratio (95% CI)0.86 [0.73, 1.00]

 2 Local disease control2929Hazard Ratio (95% CI)0.28 [0.23, 0.35]

 
Summary of findings for the main comparison. Surgery compared to primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus)

Surgery compared to primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus)

Patient or population: Women (70 years plus )with operable primary breast cancer
Settings: Hospital
Intervention: Surgery
Comparison: Primary endocrine therapy

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Primary endocrine therapySurgery

Survival - overall
Follow-up: 0 - 28 years
Study populationHR 0.98
(0.81 to 1.20)
495
(3 studies)
⊕⊕⊝⊝
low1

862 per 1000854 per 1000
(826 to 877)

Moderate

969 per 1000967 per 1000
(960 to 973)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Unselected Oestrogen receptor status. Variability of surgery undertaken. No co-morbidity assessment undertaken.
 
Summary of findings 2. Surgery plus endocrine therapy compared to primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus)

Surgery plus endocrine therapy compared to primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus)

Patient or population: Women (70 years plus) with operable primary breast cancer
Intervention: Surgery plus endocrine therapy
Comparison: Primary endocrine therapy

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Primary endocrine therapySurgery plus endocrine therapy

Survival - overall
Follow-up: 0 - 12 years
Study populationHR 0.86
(0.73 to 1)
1076
(3 studies)
⊕⊕⊝⊝
low1

617 per 1000581 per 1000
(541 to 617)

Moderate

613 per 1000577 per 1000
(536 to 613)

Local disease control
Follow-up: 0 - 12 years
Study populationHR 0.28
(0.23 to 0.35)
929
(2 studies)
⊕⊕⊕⊕
high

452 per 1000187 per 1000
(159 to 224)

Moderate

452 per 1000188 per 1000
(159 to 224)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Unselected Oestrogen receptor status. Variability of surgery undertaken. No co-morbidity assessment undertaken.
 
Table 1. Source data for comparisons

ComparisonOutcomeTrialFollow-upSummary statisticsObserved events (n)Subsection of Parmar 1998

Surgery versus primary endocrine therapySurvival - overallEORTC 10851Approximately 10 years. Surgery: median 11.7 years (95% CI: 11.2 to 12.8; range: 0 - 14.3). Primary endocrine therapy: 10.2 years (95% CI: 10.3 to 11.2; range: 0 - 14.9)Fentiman 2003: Kaplan-Meier Curves; Fmin and Fmax stated in paper.Fentiman 2003; Table 2, "Total deceased".Subsection 5

Surgery versus primary endocrine therapySurvival - overallNottingham 1Median 73 and 74 months. Maximum follow-up 20 yearsChakrabarti 2011: Kaplan-Meier Curves.Fmin taken as first event; Fmax stated in paper.Chakrabarti 2011. Table 1.Subsection 5

Surgery versus primary endocrine therapySurvival - overallSt GeorgesRange: 0 - 28 yearsGazet 2011: Kaplan-Meier CurvesGazet and Sutcliffe 2011: Table 1Subsection 5

Surgery versus primary endocrine therapyProgression-free survivalEORTC 10851Approximately 10 years. Surgery: median 11.7 years (95% CI: 11.2 to 12.8; range: 0 - 14.3). Primary endocrine therapy: 10.2 years (95% CI: 10.3 to 11.2; range: 0 - 14.9)Fentiman 2003, Table 3 (p 314): number of events and number randomised for each arm; P valueFentiman 2003; Table 3, 'Progression-free survival: number of events'Subsection 5

Surgery versus primary endocrine therapyLocal disease controlEORTC 10851Approximately 10 years. Surgery: median 11.7 years (95% CI: 11.2 to 12.8; range: 0 - 14.3). Primary endocrine therapy: 10.2 years (95% CI: 10.3 to 11.2; range: 0 - 14.9).Fentiman 2003: Kaplan-Meier Curves; Fmin and Fmax stated in paperFentiman 2003; Table 3, 'Time to loco-regional progression'Subsection 5

Surgery versus primary endocrine therapyLocal disease controlNottingham 1Median 145 months (range: 116 - 180 months)Kenny 1998: Life tablesKenny 1998; Figure 1, 'Local control by primary treatmentSubsection 5

Surgery versus primary endocrine therapyLocal disease controlSt GeorgesMedian 6 years (range 3 - 11 years)Martin Bland personal communication: Anonymised IPD from which hazard ratios and 95% confidence intervals were derived.Gazet 1994; p 208Subsection 4

Surgery versus primary endocrine therapyDistant metastasis-free survivalEORTC 10851Approximately 10 years. Surgery: median 11.7 years (95% CI: 11.2 - 12.8; range: 0 - 14.3). Primary endocrine therapy: 10.2 years (95% CI: 10.3 to 11.2; range: 0 - 14.9)Fentiman 2003: Kaplan-Meier Curves; Fmin and Fmax stated in paperFentiman 2003; Table 2, added figures for, 'Distant [relapse]" and "Local and distant'Subsection 5

Surgery versus primary endocrine therapyDistant metastasis-free survivalSt GeorgesMedian 6 years (range 3 - 11 years)Martin Bland personal communication: Anonymised IPD from which hazard ratios and 95% confidence intervals were derived (Bland 2005 [pers comm])Gazet 1994; p 210Subsection 4

Surgery plus endocrine therapy versus primary endocrine therapySurvival - overallCRCMedian 12.7 yearsFennessey 2004 p 702: Hazard ratios and 95% confidence intervalsFennessey 2004, Table 4Subsection 4

Surgery plus endocrine therapy versus primary endocrine therapySurvival - overallGRETA80 months.Mustacchi personal communication: Hazard ratios and 95% confidence intervals (Mustacchi 2005 [pers comm])Mustacchi 2003; Table 4.Subsection 4

Surgery plus endocrine therapy versus primary endocrine therapySurvival - overallNottingham 260 months.Willsher 1997: Life Table reporting grouped data; Fmin assumed the same as Nottingham 1 (same trialists, same protocol); Fmax 60 months - from life tableUsed 'effective number of deaths in t'Subsection 5

Surgery plus endocrine therapy versus primary endocrine therapyProgression-free survivalGRETA80 months.Mustacchi 2003; observed events for research and control; numbers randomised to research and control; P valueMustacchi 2003; Table 4; 'Total events.Subsection 5

Surgery plus endocrine therapy versus primary endocrine therapyLocal disease controlGRETA80 months.Mustacchi 2003; Figure 1: Kaplan-Meier CurveMustacchi 2003; Table 4; 'First local progression'Subsection 5

Surgery plus endocrine therapy versus primary endocrine therapyLocal disease controlCRCMedian 12.7 years.Hazard Ratios from Fennessey 2004 p 701; Fmin from Table 1, Fmax from last entry on curve.Fennessey 2004, Table 2, 'Local' + 'Axillary'Subsection 4