Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen

Sally Dominick; Martha Hickey; Jason Chin; H Irene Su

doi:10.1002/14651858.CD007245.pub3

Левоноргестрел‐высвобождающая внутриматочная система для защиты эндометрия женщин с раком молочной железы, получающих адъювантную терапию тамоксифеном

Appendices

Appendix 1. MDSG search (October 2015)

Keywords CONTAINS "IUD" or "levonorgestrel intrauterine system" or "levonorgestrel‐releasing intrauterine device" or "levonorgestrel‐releasing intrauterine system" or "Levonorgestrel‐Therapeutic‐Use" or "LNG‐IUS" or "LNG20"or "Intrauterine Releasing Devices" or "Intrauterine Devices Medicated" or "intrauterine devices" or "intrauterine device" or "intrauterine contraceptive devices" or "Mirena" or Title CONTAINS "IUD" or "levonorgestrel intrauterine system" or "levonorgestrel‐releasing intrauterine device" or "levonorgestrel‐releasing intrauterine system" or "Levonorgestrel‐Therapeutic‐Use" or "LNG‐IUS" or "LNG20"or "Intrauterine Releasing Devices" or "Intrauterine Devices Medicated" or "intrauterine devices" or "intrauterine device" or "intrauterine contraceptive devices" or "Mirena"

AND

Keywords CONTAINS "breast cancer" or "breast cancer incidence"or "breast changes"or "breast disease"or "breast outcomes"or "cancer risk"or "endometrial cancer"or "endometrial hyperplasia"or"endometrial pathology"or"endometrial polyps"or"endometrial proliferation"or "polyps" or Title CONTAINS "breast cancer" or "breast cancer incidence"or "breast changes"or "breast disease"or "breast outcomes"or "cancer risk"or "endometrial cancer"or "endometrial hyperplasia"or"endometrial pathology"or"endometrial polyps"or"endometrial proliferation"or "polyps"

Appendix 2. CBCG search (October 2015)

Details regarding the search strategies used by the Cochrane Breast Cancer Group for the identification of studies and procedures used to code references for the Specialised Register are outlined in the Group’s module: www.onlinelibrary.wiley.com/o/cochrane/clabout/articles/BREASTCA/frame.html

The following key words were used to identify relevant studies for consideration: "IUD", "intrauterine devices", "intrauterine system", "levonorgestrel intrauterine system", "levonorgestrel‐releasing intrauterine device", "levonorgestrel‐releasing intrauterine system", "levonorgestrel‐therapeutic use", "LNG‐IUS", "LNG20" and "Mirena".

Appendix 3. CENTRAL search (October 2015)

1 exp Breast Neoplasms/ (7208)

2 Breast Neoplasms, Male/ (23)

3 1 not 2 (7185)

4 (Breast cancer$ or Breast Neoplasm$).tw. (15233)

5 3 or 4 (16346)

6 exp Intrauterine Devices, Medicated/ (300)

7 Intrauterine Device$.tw. (350)

8 (LNG IUS or LNG IUD).tw. (133)

9 Levonorgestrel‐releasing intrauterine system$.tw. (106)

10 Levonorgestrel‐releasing intrauterine device$.tw. (43)

11 (IUD$ or Mirena).tw. (550)

12 or/6‐11 (784)

13 Intrauterine Devices, Medicated/ae [Adverse Effects] (1)

14 exp Neoplasm Recurrence, Local/ (2984)

15 exp Endometrial Hyperplasia/ (94)

16 exp Endometrial Neoplasms/ (274)

17 exp Adenocarcinoma/ (3971)

18 exp Neoplasm Metastasis/ (3273)

19 exp Antineoplastic Agents, Hormonal/ae [Adverse Effects] (346)

20 exp Tamoxifen/ae [Adverse Effects] (74)

21 breast cancer recurrence$.tw. (150)

22 recurrent breast cancer.tw. (119)

23 Local Neoplasm Recurrence$.tw. (0)

24 secondary breast cancer$.tw. (24)

25 secondary neoplasm$.tw. (11)

26 secondary cancer$.tw. (30)

27 Neoplasm Metastasis.tw. (2)

28 cancer metastasis.tw. (35)

29 advanced breast cancer.tw. (1815)

30 breast cancer survival.tw. (57)

31 Endometrial Hyperplasia.tw. (192)

32 Endometri$ patholog$.tw. (44)

33 Endometri$ polyp$.tw. (86)

34 Endometrial adenocarcinoma$.tw. (30)

35 endometrial cancer.tw. (458)

36 or/13‐35 (11723)

37 5 and 12 and 36 (6)

Appendix 4. The Cochrane Library (October 2015)

#1 "Clinical Trial" or "Phase I Clinical Trial" or "Phase II Clinical Trial" or "Phase III Clinical Trial" or "Phase IV Clinical Trial" or "Controlled Clinical Trial" or "Multicenter Study" or "Randomized Controlled Trial" or "Pragmatic Clinical Trial" in Cochrane Reviews (Reviews and Protocols) and Trials

#2 mh "Breast Neoplasms" not mh "Breast Neoplasms, Male" or "Breast cancer" or "Breast Neoplasms"

#3 mh "Intrauterine Devices" or mh "Levonorgestrel" or "Intrauterine Devices" or "IUD" or "Medicated Intrauterine Devices" or "LNG IUS" or "Levonorgestrel‐releasing intrauterine system" or "Mirena" or "Levonorgestrel"

#4 mh "Intrauterine Devices/adverse effects" or mh "Levonorgestrel/adverse effects" or mh "Neoplasm Recurrence, Local" or mh "Breast Neoplasms/secondary" or mh "Neoplasms/secondary" or mh "Endometrial Hyperplasia" or mh "Neoplasm Metastasis" or "breast cancer recurrence" or "recurrent breast cancer" or "Local Neoplasm Recurrence" or "secondary breast cancer" or "secondary neoplasms" or "secondary cancers" or "Neoplasm Metastasis" or "cancer metastasis" or "breast cancer metastasis" or "advanced breast cancer" or "breast cancer survival" or "Endometrial Hyperplasia" or "Endometrial pathology" or "Endometrial polyps" or "Endometrial adenocarcinoma" or "endometrial cancer"

#5 #1 and #2 and #3 and #4

Appendix 5. MEDLINE search (1946 to October 2015)

1 exp Breast Neoplasms/ (239438)
2 Breast Neoplasms, Male/ (2450)
3 1 not 2 (236988)
4 (Breast cancer$ or Breast Neoplasm$).tw. (200308)
5 3 or 4 (285644)
6 exp Intrauterine Devices, Medicated/ (2884)
7 Intrauterine Device$.tw. (4350)
8 (LNG IUS or LNG IUD).tw. (607)
9 Levonorgestrel‐releasing intrauterine system$.tw. (494)
10 Levonorgestrel‐releasing intrauterine device$.tw. (164)
11 (IUD$ or Mirena).tw. (8243)
12 or/6‐11 (11321)
13 Intrauterine Devices, Medicated/ae [Adverse Effects] (383)
14 exp Neoplasm Recurrence, Local/ (91623)
15 exp Endometrial Hyperplasia/ (3118)
16 exp Endometrial Neoplasms/ (16799)
17 exp Adenocarcinoma/ (308090)
18 exp Neoplasm Metastasis/ (168719)
19 exp Antineoplastic Agents, Hormonal/ae [Adverse Effects] (16203)
20 exp Tamoxifen/ae [Adverse Effects] (2944)
21 breast cancer recurrence$.tw. (1065)
22 recurrent breast cancer.tw. (1245)
23 Local Neoplasm Recurrence$.tw. (5)
24 secondary breast cancer$.tw. (72)
25 secondary neoplasm$.tw. (452)
26 secondary cancer$.tw. (853)
27 Neoplasm Metastasis.tw. (74)
28 cancer metastasis.tw. (6717)
29 advanced breast cancer.tw. (6880)
30 breast cancer survival.tw. (1012)
31 Endometrial Hyperplasia.tw. (2536)
32 Endometri$ patholog$.tw. (646)
33 Endometri$ polyp$.tw. (1202)
34 Endometrial adenocarcinoma$.tw. (2770)
35 endometrial cancer.tw. (11955)
36 or/13‐35 (546313)
37 5 and 12 and 36 (56)

Appendix 6. EMBASE search (1980 to October 2015)

1 exp breast tumor/ (388566)
2 (Breast cancer$ or Breast Neoplasm$).tw. (266249)
3 breast tumor$.tw. (19642)
4 or/1‐3 (416695)
5 exp intrauterine contraceptive device/ (14353)
6 Intrauterine Device$.tw. (4807)
7 (LNG IUS or LNG IUD).tw. (926)
8 Levonorgestrel‐releasing intrauterine system$.tw. (647)
9 Levonorgestrel‐releasing intrauterine device$.tw. (202)
10 (IUD$ or Mirena).tw. (7409)
11 or/5‐10 (16901)
12 intrauterine contraceptive device/ae [Adverse Drug Reaction] (1458)
13 exp tumor recurrence/ (43045)
14 exp endometrium hyperplasia/ (6121)
15 exp endometrium tumor/ (44939)
16 exp breast adenocarcinoma/ or exp adenocarcinoma/ (84246)
17 exp metastasis/ (435415)
18 "antineoplastic hormone agonists and antagonists"/ae [Adverse Drug Reaction] (541)
19 exp tamoxifen/ae [Adverse Drug Reaction] (6669)
20 breast cancer recurrence$.tw. (1657)
21 recurrent breast cancer$.tw. (1589)
22 Local Neoplasm Recurrence$.tw. (5)
23 secondary breast cancer$.tw. (132)
24 secondary neoplasm$.tw. (602)
25 secondary cancer$.tw. (1265)
26 Neoplasm Metastasis.tw. (83)
27 cancer metastasis.tw. (8860)
28 advanced breast cancer.tw. (9170)
29 breast cancer survival.tw. (1254)
30 Endometrial Hyperplasia.tw. (3303)
31 Endometri$ patholog$.tw. (961)
32 Endometri$ polyp$.tw. (1881)
33 Endometrial adenocarcinoma$.tw. (3393)
34 endometrial cancer.tw. (16312)
35 or/12‐34 (589755)
36 4 and 11 and 35 (164)
37 Clinical Trial/ (851926)
38 Randomized Controlled Trial/ (386357)
39 exp randomization/ (68465)
40 Single Blind Procedure/ (21150)
41 Double Blind Procedure/ (124284)
42 Crossover Procedure/ (44751)
43 Placebo/ (264658)
44 Randomi?ed controlled trial$.tw. (125251)
45 Rct.tw. (18496)
46 random allocation.tw. (1460)
47 randomly allocated.tw. (23462)
48 allocated randomly.tw. (2066)
49 (allocated adj2 random).tw. (739)
50 Single blind$.tw. (16466)
51 Double blind$.tw. (155581)
52 ((treble or triple) adj blind$).tw. (494)
53 placebo$.tw. (222116)
54 prospective study/ (310814)
55 or/37‐54 (1512736)
56 case study/ (34158)
57 case report.tw. (292453)
58 abstract report/ or letter/ (941185)
59 or/56‐58 (1261247)
60 55 not 59 (1472739)
61 exp Meta Analysis/ (100433)
62 ((meta adj analy$) or metaanalys$).tw. (108700)
63 (systematic adj (review$1 or overview$1)).tw. (89312)
64 review.ti. (340162)
65 or/61‐64 (470737)
66 60 or 65 (1842276)
67 36 and 66 (69)

Appendix 7. CINAHL search (1982 to October 2015)

#	Query	Results
S14	S6 AND S13	35
S13	S7 OR S8 OR S9 OR S10 OR S11 OR S12	2,313
S12	TX(IUD* or Mirena*)	744
S11	TX (Levonorgestrel‐releasing intrauterine)	175
S10	TX (LNG IUD)	15
S9	TX (LNG IUS)	78
S8	TX Intrauterine Device*	2,065
S7	(MM "Intrauterine Devices")	1,107
S6	S1 OR S2 OR S3 OR S4 OR S5	61,738
S5	TX (Breast cancer* or Breast Neoplasm*)	61,494
S4	TX (Breast cancer* or Breast Neoplasm*).tw	1
S3	TX breast tumour*	451
S2	TX breast tumor*	2,002
S1	(MM "Breast Neoplasms+")	43,927

Appendix 8. PyscINFO (October 2015)

1 exp Intrauterine Devices/ (91)

2 Levonorgestrel.tw. (62)

3 intrauterine device$.tw. (174)

4 iud.tw. (131)

5 mirena.tw. (9)

6 intrauterine system$.tw. (26)

7 exp Breast Neoplasms/ (7066)

8 breast neoplasm$.tw. (40)

9 breast tumor$.tw. (73)

10 (breast adj5 ca).tw. (1)

11 (breast adj5 cancer$).tw. (9414)

12 or/1‐6 (303)

13 or/7‐11 (9639)

14 12 and 13 (1)

Appendix 9. PubMed search (1946 to October 2015)

(("Clinical Trial"[Publication Type]) OR ("Phase I Clinical Trial" OR "Phase II Clinical Trial" OR "Phase III Clinical Trial" OR "Phase IV Clinical Trial" OR "Controlled Clinical Trial" OR "Multicenter Study" OR "Randomized Controlled Trial" OR "Pragmatic Clinical Trial"))

AND

(("Breast Neoplasms"[Mesh] NOT "Breast Neoplasms, Male"[Mesh]) OR ("Breast cancer" OR "Breast Neoplasms"))

AND

(("Intrauterine Devices, Medicated"[Mesh]) OR ("Intrauterine Devices" OR "IUD" OR "Medicated Intrauterine Devices" OR "LNG IUS" OR "Levonorgestrel‐releasing intrauterine system" OR "Mirena"))

AND

(("Intrauterine Devices, Medicated/adverse effects"[Mesh]) OR ("Neoplasm Recurrence, Local"[Mesh] OR "Breast Neoplasms/secondary"[Mesh] OR "Neoplasms/secondary"[Mesh] OR "Endometrial Hyperplasia"[Mesh] OR "Endometrial Neoplasms"[Mesh] OR "Adenocarcinoma" [Mesh] OR "Neoplasm Metastasis"[Mesh] OR "Antineoplastic Agents, Hormonal/adverse effects"[Mesh] OR "Tamoxifen/adverse effects"[Mesh]) OR ("breast cancer recurrence" OR "recurrent breast cancer" OR "Local Neoplasm Recurrence" OR "secondary breast cancer" OR "secondary neoplasms" OR "secondary cancers" OR "Neoplasm Metastasis" OR "cancer metastasis" OR "breast cancer metastasis" OR "advanced breast cancer" OR "breast cancer survival" OR "Endometrial Hyperplasia" OR "Endometrial pathology" OR "Endometrial polyps" OR "Endometrial adenocarcinoma" OR "endometrial cancer"))

Figure 1

Study flow diagram

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Figure 2

Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies

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Figure 3

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

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Figure 4

Forest plot of comparison: 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, outcome: 1.1 Endometrial Polyps.

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Figure 5

Forest plot of comparison: 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, outcome: 1.2 Endometrial Hyperplasia.

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Figure 6

Forest plot of comparison: 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, outcome: 1.4 Fibroids.

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Figure 7

Forest plot of comparison: 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, outcome: 1.5 Abnormal Vaginal Bleeding or Spotting.

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Figure 8

Forest plot of comparison: 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, outcome: 1.6 Breast Cancer Recurrence.

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Figure 9

Forest plot of comparison: 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, outcome: 1.7 Breast Cancer‐related Death.

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Analysis 1.1

Comparison 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, Outcome 1 Endometrial Polyps.

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Analysis 1.2

Comparison 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, Outcome 2 Endometrial Hyperplasia.

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Analysis 1.3

Comparison 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, Outcome 3 Endometrial Cancer.

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Analysis 1.4

Comparison 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, Outcome 4 Fibroids.

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Analysis 1.5

Comparison 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, Outcome 5 Abnormal Vaginal Bleeding or Spotting.

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Analysis 1.6

Comparison 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, Outcome 6 Breast Cancer Recurrence.

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Analysis 1.7

Comparison 1 LNG‐IUS with endometrial surveillance versus endometrial surveillance alone, Outcome 7 Breast Cancer‐related Death.

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Summary of findings for the main comparison. The LNG‐IUS with endometrial surveillance compared to endometrial surveillance alone for endometrial protection in women with breast cancer on adjuvant tamoxifen

The LNG‐IUS with endometrial surveillance compared to endometrial surveillance alone for endometrial protection in women with breast cancer on adjuvant tamoxifen
Patient or population: endometrial protection in women with breast cancer on adjuvant tamoxifen Setting: hospital, outpatient clinic Intervention: LNG‐IUS with endometrial surveillance Comparison: endometrial surveillance alone
Outcomes	*Illustrated comparative risks^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed Risk	Corresponding Riks
	Endometrial surveillance alone	LNG‐IUS with endometrial surveillance
Endometrial Polyps follow up: range 24 months to 60 months	Moderate		OR 0.22 (0.13 to 0.39)	417 (4 RCTs)	⊕⊕⊕⊝ MODERATE ¹
	235 per 1000	63 per 1000 (38 to 107)
Endometrial Hyperplasia follow up: range 24 months to 60 months	Moderate		OR 0.13 (0.03 to 0.67)	417 (4 RCTs)	⊕⊕⊕⊝ MODERATE ¹
	28 per 1000	4 per 1000 (1 to 19)
Endometrial Cancer follow up: range 24 months to 60 months	Moderate		not estimable	154 (2 RCTs)	⊕⊕⊕⊝ MODERATE ¹
	0 per 1000	0 per 1000 (0 to 0)
Fibroids follow up: range 12 months to 24 months	Moderate		OR 0.48 (0.16 to 1.46)	314 (3 RCTs)	⊕⊕⊕⊝ MODERATE ¹
	58 per 1000	29 per 1000 (10 to 82)
Abnormal Vaginal Bleeding or Spotting follow up: 12 months	Moderate		OR 7.26 (3.37 to 15.66)	376 (3 RCTs)	⊕⊕⊕⊝ MODERATE ¹
	17 per 1000	113 per 1000 (56 to 215)
Abnormal Vaginal Bleeding or Spotting follow up: 24 months	Moderate		OR 2.72 (1.04 to 7.10)	233 (2 RCTs)	⊕⊕⊕⊝ MODERATE ¹
	42 per 1000	107 per 1000 (44 to 239)
Abnormal Vaginal Bleeding or Spotting follow up: 60 months	Moderate		not estimable	94 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹
	0 per 1000	0 per 1000 (0 to 0)
Breast Cancer Recurrence follow up: range 24 months to 60 months	Moderate		OR 1.74 (0.64 to 4.74)	154 (2 RCTs)	⊕⊕⊕⊝ MODERATE ¹
	80 per 1000	131 per 1000 (53 to 291)
Breast Cancer‐related Death follow up: range 12 months to 60 months	Moderate		OR 1.02 (0.36 to 2.84)	277 (3 RCTs)	⊕⊕⊕⊝ MODERATE ¹
	69 per 1000	70 per 1000 (26 to 174)
The basis for the assumed risk* is the median control group risk across studies. 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: 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
¹ limited sample size and low event rate

Summary of findings for the main comparison. The LNG‐IUS with endometrial surveillance compared to endometrial surveillance alone for endometrial protection in women with breast cancer on adjuvant tamoxifen

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Table 1. Chan 2007 & Wong 2013

	Treatment Group	Control	P value
6 months follow‐up
Randomised	64	65
Completed	55	58

Abnormal vaginal bleeding or spotting	20	1	<0.001

12 months follow‐up
Completed	55	58

Abnormal vaginal bleeding or spotting	6	1	0.06
Endometrial polyps	1	9	0.02
Endometrial hyperplasia	0	0
Fibroids	1	2	1.0

24 months follow‐up
Completed	55	57

Abnormal vaginal bleeding or spotting	6	3	0.45

45 months follow‐up
Completed	48	52

Abnormal vaginal bleeding or spotting	0	0

60 months follow‐up
Completed	46	48

Abnormal vaginal bleeding or spotting	0	0
Endometrial polyps	2	16	< 0.001
Endometrial hyperplasia	0	1	1.0
Endometrial cancer	0	0
Fibroids	1	2	1.0
Breast cancer recurrence	10	6	0.25
Breast cancer‐related deaths	6	5	0.71

Table 1. Chan 2007 & Wong 2013

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Table 2. Gardner 2000 & 2009

	Treatment Group	Control	P value
12 months follow‐up
Randomised	64	58
Completed	47	52

Endometrial polyps	1	4	0.4
Endometrial hyperplasia	0	1
Fibroids	1	3	0.2

Final follow‐up (24, 36, or 48 months)
Completed at 24 months	31	29
Completed at 36 months	19	20
Completed at 48 months	6	9

Endometrial polyps	3	8
Endometrial hyperplasia	0	1
Endometrial cancer	0	0
Breast cancer recurrence	1	1
Breast cancer‐related deaths	2	2

Table 2. Gardner 2000 & 2009

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Table 3. Kesim 2008

	Treatment Group	Control	P value
5 months follow‐up
Randomised	70	72
Completed	70	72

Abnormal vaginal bleeding or spotting	7	0

12 months follow‐up
Randomised	70	72
Completed	70	72

Abnormal vaginal bleeding or spotting	0	0

36 months follow‐up
Randomised	70	72
Completed	70	72

Endometrial polyps	4	14	< 0.05
Endometrial hyperplasia	0	4	< 0.05

Table 3. Kesim 2008

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Table 4. Omar 2010

	Treatment Group	Control	P value
12 months follow‐up
Randomised	75	75
Completed	60	63

Abnormal vaginal bleeding or spotting	22	2	<0.001
Breast cancer‐related deaths	0	1

24 months follow‐up
Completed	59	62

Abnormal vaginal bleeding or spotting	7	2	0.08
Endometrial polyps	1	10	0.02
Endometrial hyperplasia	0	0
Fibroids	2	4	1.0

Table 4. Omar 2010

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Comparison 1. LNG‐IUS with endometrial surveillance versus endometrial surveillance alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Endometrial Polyps Show forest plot	4		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

1.1 Short term follow‐up (12 months)	2	212	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.22 [0.08, 0.64]
1.2 Long term follow‐up (24 to 60 months)	4	417	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.22 [0.13, 0.39]
2 Endometrial Hyperplasia Show forest plot	4	417	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.13 [0.03, 0.67]

3 Endometrial Cancer Show forest plot	2	154	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]

4 Fibroids Show forest plot	3	314	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.48 [0.16, 1.46]

5 Abnormal Vaginal Bleeding or Spotting Show forest plot	3		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

5.1 12 months	3	376	Peto Odds Ratio (Peto, Fixed, 95% CI)	7.26 [3.37, 15.66]
5.2 24 months	2	233	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.72 [1.04, 7.10]
5.3 45 months	1	100	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.4 60 months	1	94	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Breast Cancer Recurrence Show forest plot	2	154	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.74 [0.64, 4.74]

7 Breast Cancer‐related Death Show forest plot	3	277	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.02 [0.36, 2.84]

Comparison 1. LNG‐IUS with endometrial surveillance versus endometrial surveillance alone

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Левоноргестрел‐высвобождающая внутриматочная система для защиты эндометрия женщин с раком молочной железы, получающих адъювантную терапию тамоксифеном

Appendices

Appendix 1. MDSG search (October 2015)

Appendix 2. CBCG search (October 2015)

Appendix 3. CENTRAL search (October 2015)

Appendix 4. The Cochrane Library (October 2015)

Appendix 5. MEDLINE search (1946 to October 2015)

Appendix 6. EMBASE search (1980 to October 2015)

Appendix 7. CINAHL search (1982 to October 2015)

Appendix 8. PyscINFO (October 2015)

Appendix 9. PubMed search (1946 to October 2015)

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Appendices

Appendix 1. MDSG search (October 2015)

Appendix 2. CBCG search (October 2015)

Appendix 3. CENTRAL search (October 2015)

Appendix 4. The Cochrane Library (October 2015)

Appendix 5. MEDLINE search (1946 to October 2015)

Appendix 6. EMBASE search (1980 to October 2015)

Appendix 7. CINAHL search (1982 to October 2015)

Appendix 8. PyscINFO (October 2015)

Appendix 9. PubMed search (1946 to October 2015)

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