Breast surgery for metastatic breast cancer

Giuliano Tosello; Maria Regina Torloni; Bruna S Mota; Teresa Neeman; Rachel Riera

doi:10.1002/14651858.CD011276.pub2

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Figure 1

Study flow diagram.

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 3

Forest plot of comparison: 1 Systemic treatment plus surgery versus systemic treatment, outcome: 1.1 Overall survival.

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Figure 4

Forest plot of comparison: 1 Systemic treatment plus surgery versus systemic treatment, outcome: 1.5 Progression‐free survival.

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Analysis 1.1

Comparison 1 Systemic treatment plus surgery versus systemic treatment, Outcome 1 Overall survival.

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Analysis 1.2

Comparison 1 Systemic treatment plus surgery versus systemic treatment, Outcome 2 Overall survival ‐ HER2 status.

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Analysis 1.3

Comparison 1 Systemic treatment plus surgery versus systemic treatment, Outcome 3 Overall survival ‐ ER status.

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Analysis 1.4

Comparison 1 Systemic treatment plus surgery versus systemic treatment, Outcome 4 Overall survival ‐ only bone metastasis.

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Analysis 1.5

Comparison 1 Systemic treatment plus surgery versus systemic treatment, Outcome 5 Progression‐free survival.

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Summary of findings for the main comparison. Breast surgery plus systemic treatment compared to systemic treatment for metastatic breast cancer

Breast surgery plus systemic treatment compared to systemic treatment for metastatic breast cancer
Patient or population: metastatic breast cancer Setting: inpatients and outpatients Intervention: breast surgery plus systemic treatment Comparison: systemic treatment
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with systemic treatment	Risk with breast surgery plus systemic treatment
Overall survival at 2 years Follow‐up: range 23 months to 40 months	Study population		HR 0.83 (0.53 to 1.31)	624 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 2 3}	The estimates for the control group are based upon an average of the estimates from Badwe 2015 and Soran 2016.
	511 per 1000	448 per 1000 (318 to 608)
Quality of life	Not reported	Not reported	‐	‐	‐
Local PFS at 2 years Follow‐up: range 23 months to 40 months	Study population		HR 0.22 (0.08 to 0.57)	607 (2 RCTs)	⊕⊕⊝⊝ LOW ^{2 4}	The estimates for the control group are based upon an average of the estimates from Badwe 2015 and Soran 2016.
	500 per 1000	141 per 1000 (54 to 326)
Distant PFS at 2 years Follow‐up: 23 months	Study population		HR 1.42 (1.08 to 1.86)	350 (1 RCT)	⊕⊕⊕⊝ MODERATE ⁵	The estimates for the control group are based upon the estimates from Badwe 2015.
	548 per 1000	676 per 1000 (576 to 772)
Breast cancer‐specific survival	Not reported	Not reported	‐	‐	‐
Toxicity from local therapy Follow‐up: 40 months	Study population		RR 0.99 (0.14 to 6.90)	274 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 6}	The estimates for the control group are based upon the estimates from Soran 2016.
	15 per 1000	15 per 1000 (2 to 101)
*The risk in the intervention group (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; HR: hazard ratio; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
¹In Soran 2016, trial random sequence generation and allocation concealment were unclear. Downgraded one level. ²Statistical or clinical heterogeneity, or both. Downgraded one level. ³Wide 95% CI (0.53 to 1.31) including the null effect. Downgraded one level. ⁴In Soran 2016, trial random sequence generation and allocation concealment were unclear. Outcome assessors were not blinded, and this is a subjective outcome. Downgraded one level. ⁵Outcome assessors were not blinded, and this is a subjective outcome. Downgraded one level. ⁶Very wide 95% CI (0.14 to 6.9). Downgraded one level.

Summary of findings for the main comparison. Breast surgery plus systemic treatment compared to systemic treatment for metastatic breast cancer

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Table 1. Overall survival ‐ subgroup analyses

Overall survival subgroup analysis	Number of studies	N	HR	Lower CI	Upper CI	P value
HER2‐positive	2	192	0.90	0.60	1.35	NS
HER2‐negative	2	421	0.85	0.67	1.08	NS
ER positive	2	426	0.79	0.61	1.03	NS
ER negative	2	200	1.01	0.73	1.40	NS
Bone‐only metastasis	2	226	0.91	0.49	1.69	NS
CI: confidence interval ER: oestrogen receptor HR: hazard ratio NS: not significant

Table 1. Overall survival ‐ subgroup analyses

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Comparison 1. Systemic treatment plus surgery versus systemic treatment

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival Show forest plot	2	624	Hazard Ratio (Random, 95% CI)	0.83 [0.53, 1.31]

2 Overall survival ‐ HER2 status Show forest plot	2		Hazard Ratio (Random, 95% CI)	Subtotals only

2.1 HER2‐positive	2	192	Hazard Ratio (Random, 95% CI)	0.85 [0.48, 1.50]
2.2 HER2‐negative	2	421	Hazard Ratio (Random, 95% CI)	0.84 [0.50, 1.40]
3 Overall survival ‐ ER status Show forest plot	2		Hazard Ratio (Random, 95% CI)	Subtotals only

3.1 ER‐positive	2	426	Hazard Ratio (Random, 95% CI)	0.83 [0.48, 1.42]
3.2 ER‐negative	2	200	Hazard Ratio (Random, 95% CI)	1.04 [0.70, 1.55]
4 Overall survival ‐ only bone metastasis Show forest plot	2	226	Hazard Ratio (Random, 95% CI)	0.91 [0.49, 1.69]

5 Progression‐free survival Show forest plot	2		Hazard Ratio (Random, 95% CI)	Subtotals only

5.1 Local progression‐free survival	2		Hazard Ratio (Random, 95% CI)	0.22 [0.08, 0.57]
5.2 Distant progression‐free survival	1		Hazard Ratio (Random, 95% CI)	1.42 [1.08, 1.86]

Comparison 1. Systemic treatment plus surgery versus systemic treatment

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