Searches

Heidi D Nelson; Rochelle Fu; Linda Humphrey; ME Beth Smith; Jessica C Griffin; Peggy Nygren

This publication is provided for historical reference only and the information may be out of date.

Appendix ASearches

Publication Details

Appendix A-1. Search Strategies

MEDLINE Searches

Appendix A-2. Inclusion and Exclusion Criteria By Key Question

Randomized, double-blind, placebo controlled trials of tamoxifen, raloxifene, or tibolone for breast cancer prevention. Head-to-head trials that include direct comparisons between tamoxifen, raloxifene, or tibolone.

Publication Details

Copyright

Publisher

Agency for Healthcare Research and Quality (US), Rockville (MD)

NLM Citation

Nelson HD, Fu R, Humphrey L, et al. Comparative Effectiveness of Medications To Reduce Risk of Primary Breast Cancer in Women [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 Sep. (AHRQ Comparative Effectiveness Reviews, No. 17.) Appendix A, Searches.

Ovid MEDLINE(R) <1950 to January Week 3 2009>
KEY QUESTIONS 2, 3, 4, 5
Search Strategy:
1	selective estrogen receptor modulators/or raloxifene/or tamoxifen
2	exp Breast Neoplasms/pc [Prevention & Control]
3	1 and 2
4	Primary Prevention
5	(primar$ adj2 prevent$).mp. [mp=title, original title, abstract, name of substance word, subject heading word]
6	exp Breast Neoplasms
7	1 and 4 and 6
8	Chemoprevention
9	chemoprevent$.mp.
10	1 and 6 and 9
11	1 and 5 and 6
12	10 or 11
13	(prevent$ adj3 (breast$ adj2 (neoplas$ or tumor$ or cancer$ or malignan$))).mp. [mp=title, original title, abstract, name of substance word, subject heading word]
14	1 and 13
15	6 and 14
16	12 or 15
17	limit 16 to humans
18	limit 17 to english language
19	limit 17 to abstracts
20	18 or 19

Database: Ovid MEDLINE(R) <1996 to January Week 3 2009>
KEY QUESTIONS 1, 2, 3
Search Strategy:
1	exp Tamoxifen/ae, po, to
2	exp Raloxifene/ae, to, po
3	exp Placebos/or placebo$.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
4	exp Breast Neoplasms/
5	1 and 2
6	1 and 3
7	2 and 3
8	4 and 5
9	4 and 6
10	4 and 7
11	random$.mp.
12	exp Randomized Controlled Trials/
13	randomized controlled trial.pt.
14	rct$.mp.
15	11 or 12 or 13 or 14
16	8 and 15
17	9 and 15
18	10 and 15
19	16 or 17 or 18
20	exp Cardiovascular Diseases/ep, et [Epidemiology, Etiology]
21	exp Endometrial Neoplasms/ep, et [Epidemiology, Etiology]
22	exp tamoxifen/
23	exp raloxifene/
24	20 or 21
25	22 and 23
26	3 and 22
27	3 and 23
28	25 or 26 or 27
29	24 and 28
30	15 and 29
31	19 or 30
32	(200705$ or 200706$ or 200707$ or 200708$ or 200709$ or 20071$ or 2008$).ed. (634348)
33	31 and 32

Database: Ovid MEDLINE(R) <1996 to January Week 3 2009>
KEY QUESTIONS 1, 2, 3
Search Strategy:
1	exp Breast Neoplasms/pc [Prevention & Control]
2	exp Ovarian Neoplasms/pc [Prevention & Control]
3	1 or 2
4	(family adj5 histor$).mp. [mp=title, original title, abstract, name of substance word, subject heading word]
5	exp Genetic Predisposition to Disease/
6	brca.mp.
7	(brca1 or brca2).mp. [mp=title, original title, abstract, name of substance word, subject heading word]
8	4 or 5 or 6 or 7
9	exp Selective Estrogen Receptor Modulators/
10	(serm or serms or tamoxifen or raloxifene).mp. [mp=title, original title, abstract, name of substance word, subject heading word]
11	9 or 10
12	3 and 8 and 11
13	exp Contraceptives, Oral/
14	3 and 8 and 13

Database: Ovid MEDLINE(R) <1950 to January Week 3 2009>
KEY QUESTIONS 2, 3
Search Strategy:
1	exp Tamoxifen/
2	exp Raloxifene/
3	1 or 2
4	exp Tamoxifen/ae, po, to
5	exp raloxifene/ae, po, to
6	4 or 5
7	exp Genital Diseases, Female/ci, ep, et [Chemically Induced, Epidemiology, Etiology]
8	exp Genital Diseases, Female/
9	8 and 6
10	3 and 7
11	10 or 9

Database: Ovid MEDLINE(R) <1950 to January Week 3 2009>
KEY QUESTIONS 2, 3
Search Strategy:
1	exp Tamoxifen/ae, po, to
2	exp raloxifene/ae, po, to
3	1 or 2
4	exp Uterine Diseases/
5	exp uterus/
6	4 or 5
7	3 and 6
8	exp Hysterectomy/
9	3 and 8
10	7 or 9
11	limit 10 to (english language and humans)

Database: Ovid MEDLINE(R) <1950 to January Week 3 2009>
KEY QUESTIONS 2, 3
Search Strategy:
1	(ovar$ adj5 (cancer$ or tumor$ or malignan$ or carcino$ or neoplas$)).mp. [mp=title, original title, abstract, name of substance word, subject heading word]
2	exp tamoxifen/
3	exp raloxifene/
4	2 or 3
5	4 and 1
6	limit 5 to humans

Database: Ovid MEDLINE(R) <1950 to January Week 3 2009>
KEY QUESTIONS 2, 3
Search Strategy:
1	exp Tamoxifen/ae, po, ct, to [Adverse Effects, Poisoning, Contraindications, Toxicity]
2	exp Raloxifene/ae, ct, to [Adverse Effects, Contraindications, Toxicity]
3	Selective Estrogen Receptor Modulators/ae, co, to, po
4	1 or 2 or 3
5	exp Cardiovascular Diseases/mo, ci, co, ep, et [Mortality, Chemically Induced, Complications, Epidemiology, Etiology]
6	exp Stroke/mo, co, ci, ep, et
7	exp Cardiovascular System/pp, de
8	5 or 6 or 7
9	4 and 8
10	exp Cardiovascular System/
11	exp Cardiovascular Diseases/
12	10 or 11
13	exp Tamoxifen/
14	exp Raloxifene/
15	Selective Estrogen Receptor Modulators/
16	13 or 14 or 15
17	4 and 12
18	8 and 16
19	17 or 18
20	limit 9 to humans
21	limit 19 to humans
22	21 not 20
23	12 and 16
24	limit 23 to humans
25	24 not 21

Database: Ovid MEDLINE(R) <1950 to January Week 3 2009>
KEY QUESTIONS 2, 3
Search Strategy:
1	exp Tamoxifen/
2	exp Raloxifene/
3	Selective Estrogen Receptor Modulators/
4	1 or 2 or 3
5	((heart$ or myocardi$ or cardi$ or atria$ or ventric$) adj5 (fibril$ or arrhythm$ or (abnormal$ adj2 rhythm$))).mp. [mp=title, original title, abstract, name of substance word, subject heading word]
6	5 and 4
7	(tamoxifen or raloxifene).mp. [mp=title, original title, abstract, name of substance word, subject heading word]
8	5 and 7
9	8 or 6

Database: Ovid MEDLINE(R) <1950 to January Week 3 2009>
KEY QUESTIONS 2, 3
Search Strategy:
1	exp biliary tract/
2	exp biliary tract diseases/
3	1 or 2
4	exp Tamoxifen/
5	exp Raloxifene/
6	Selective Estrogen Receptor Modulators/
7	4 or 5 or 6
8	3 and 7
9	limit 8 to humans
10	(gallstone$ or gall stone$ or gallbladder$ or gall bladder$ or bile duct$ or biliary tract$ or cholelith$ or CHOLECYST$ or CHOLEDOCHOLITH$).mp.
11	7 and 10
12	limit 11 to humans
13	9 or 12

Database: Ovid MEDLINE(R) <1950 to January Week 3 2009>
KEY QUESTIONS 2, 3, 4
Search Strategy:
1	tibolone.mp.
2	exp Breast Neoplasms/
3	exp Breast/
4	or 2
5	4 and 1

Database: Ovid MEDLINE(R) <1950 to January Week 3 2009>
KEY QUESTION 5
Search Strategy:
1	exp Breast Neoplasms/
2	exp risk/
3	1 and 2
4	exp risk assessment/
5	1 and 4
6	limit 5 to humans
7	exp breast neoplasms/ep, et
8	4 and 7
9	exp Breast Neoplasms/pc, eh
10	exp Breast Neoplasms/ge
11	4 and 9
12	4 and 10
13	exp Disease Susceptibility/
14	7 and 13
15	9 and 13
16	8 or 11 or 14 or 15
17	limit 16 to (english language and humans)
18	(model$ or valid$).mp. [mp=title, original title, abstract, name of substance word, subject heading word]
19	17 and 18
20	seer.mp.
21	17 and 20
22	19 or 21
23	17 not 22

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <4^th Quarter 2008>
KEY QUESTIONS 1, 2, 3
Search Strategy:
1	tamoxifen.mp. [mp=title, original title, abstract, mesh headings, heading words, keyword]
2	raloxifene.mp. [mp=title, original title, abstract, mesh headings, heading words, keyword]
3	placebo$.mp. [mp=title, original title, abstract, mesh headings, heading words, keyword]
4	1 and 2
5	1 and 3
6	2 and 3
7	4 or 5 or 6
8	((breast$ or mammar$) adj5 (cancer$ or tumor$ or carcino$ or adenocarcin$ or neoplas$ or malignan$)).mp.
9	7 and 8

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <4^th Quarter 2008>
KEY QUESTIONS 2, 3
Search Strategy:
1	((tamoxifen or raloxifene) adj5 (endometri$ or uterine or uterus or hysterect$)).mp. [mp=title, original title, abstract, mesh headings, heading words, keyword]

Database: EBM Reviews - Cochrane Database of Systematic Reviews <4th Quarter 2008>
KEY QUESTIONS 2, 3
Search Strategy:
1	((tamoxifen or raloxifene) adj5 (endometri$ or uterine or uterus or hysterect$)).mp. [mp=title, abstract, full text, keywords, caption text]

Database: EBM Reviews - Database of Abstracts of Reviews of Effects <4th Quarter 2008>
KEY QUESTIONS 2, 3
Search Strategy:
1	((tamoxifen or raloxifene) adj5 (endometri$ or uterine or uterus or hysterect$)).mp. [mp=title, full text, keywords]

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <4^th Quarter 2008>
KEY QUESTIONS 2, 3
Search Strategy:
1	tibolone.mp.

Database: EBM Reviews - Cochrane Database of Systematic Reviews <4th Quarter 2008>
KEY QUESTIONS 2, 3
Search Strategy:
1	tibolone.mp.

Database: EBM Reviews - Database of Abstracts of Reviews of Effects <4th Quarter 2008>
KEY QUESTIONS 2, 3
Search Strategy:
1	tibolone.mp.

Key Questions	Include	Exclude	Duration and size of study	Outcomes
1. Benefits^* 3. Benefits among population subgroups^†	Randomized, double-blind, placebo controlled trials of tamoxifen, raloxifene, or tibolone for breast cancer prevention. Head-to-head trials that include direct comparisons between tamoxifen, raloxifene, or tibolone. Trials report breast cancer results as primary or secondary outcomes.^‡ Trials enroll women without pre-existing breast cancer and can include women of all ages, pre or postmenopausal status, hysterectomy or nonhysterectomy status, US and non US. English language publications.	Non RCT study designs. Non breast cancer prevention studies. Women with pre-existing breast cancer, known precursor conditions, or known carriers of breast cancer susceptibility mutations (BRCA1, BRCA2, or others). Drugs other than tamoxifen, raloxifene, or tibolone. No breast cancer results as primary or secondary outcomes. Laboratory or animal studies. Non-English language publications.	≥3 months ≥100 participants	Primary or secondary breast cancer outcomes; other benefits defined by key question 1.
2. Harms^§ 3. Harms among population subgroups^†	Randomized, double-blind, placebo controlled trials of tamoxifen, raloxifene, or tibolone. Head-to-head trials that include direct comparisons between tamoxifen, raloxifene, or tibolone. Observational studies that report results for women using tamoxifen, raloxifene, or tibolone and compares results to a nonuser group or compares results between these drug use groups. Studies enroll women without pre-existing breast cancer and can include women of all ages, pre or postmenopausal status, hysterectomy or nonhysterectomy status, US and non US. Health outcomes.^‡ English language publications.	Women with pre-existing breast cancer, known precursor conditions, or known carriers of breast cancer susceptibility mutations (BRCA1 BRCA2, or others). Drugs other than tamoxifen, raloxifene, or tibolone. No harms results. Intermediate outcomes rather than health outcomes.^‡ Laboratory or animal studies. Non-English language publications.	≥3 months ≥100 participants	Any health outcome defined by key question 2.
4. Treatment adherence, persistence, concordance, or treatment choice^†	Randomized, double-blind, placebo controlled trials of tamoxifen, raloxifene, or tibolone for breast cancer prevention. Head-to-head trials that include direct comparisons between tamoxifen, raloxifene, or tibolone. Observational and descriptive studies that report results for women using tamoxifen, raloxifene, or tibolone and compares results to a nonuser group or compares results between these drug use groups. Trials enroll women without pre-existing breast cancer and can include women of all ages, pre or postmenopausal status, hysterectomy or nonhysterectomy status, US and non US. Observational and descriptive studies of treatment choice. Studies include data for treatment adherence, persistence, concordance, or treatment choice. English language publications.	Women with pre-existing breast cancer, known precursor conditions, or known carriers of breast cancer susceptibility mutations (BRCA1, BRCA2, or others). Drugs other than tamoxifen, raloxifene, or tibolone. No adherence, persistence, concordance, or treatment choice data. Laboratory or animal studies. Non-English language publications.	RCTS: >3 months and >100 participants	Any measure of treatment adherence, persistence, or concordance; data on treatment choice.
5. Clinical risk assessment models	Studies of risk stratification models for women of any age. Models used to identify women at higher than average risk for breast cancer. Derivation or validation studies. Study must include discriminatory accuracy of the model. Models must be applicable to the primary care setting. English language publications.	Family history/genetics models designed to determine risk for BRCA mutations. Studies of individual risk factors. Laboratory tests. Non-English language publications.	Not specified.	Evaluation of risk models for breast cancer that include more than 1 risk factor.

*

Benefit outcomes are defined by key question 1 and include:

Invasive breast cancer
Noninvasive breast cancer including ductal carcinoma in situ (DCIS)
Breast cancer mortality
All-cause mortality
Osteoporotic fractures

†: Population subgroups are defined by key question 3 and include but are not limited to those based on:
Age, menopausal status (pre-, peri-, postmenopausal), hysterectomy status, use of exogenous estrogen, level of risk of breast cancer (based on family history, body mass index, parity [number of pregnancies], age at first live birth, age at menarche, personal history of breast abnormalities, prior breast biopsy, estradiol levels, breast density), ethnicity and race, metabolism status (CYP 2D6 mutation), and risk for thromboembolic events (obesity, and other risk factors).

‡

Definitions of types of outcomes:

A primary outcome is the main outcome of a study that the study was designed and powered to demonstrate.
A secondary outcome is a major outcome of a study that the study was designed and powered to demonstrate, but is not the primary outcome of the study.
Health outcomes are signs, symptoms, conditions, or events that individuals experience, such as myocardial infarction, death, or hot flahes.
Intermediate outcomes are health measures that individuals do not personally experience, such as a laboratory test results or bone mineral density.

§

Harms outcomes are defined by key question 2 and may include but are not limited to:

Thromboembolic events (deep vein thrombosis, pulmonary embolism)
Cardiovascular events (coronary heart disease, stroke and transient ischemic attack, arrhythmias)
Metabolic disorders (diabetes)
Musculoskeletal symptoms (myalgia, leg cramps)
Mental health (depression, mood changes)
Genitourinary outcomes (vaginal dryness, uterine bleeding, hysterectomy, endometrial cancer, urinary symptoms)
Adverse breast outcomes (biopsies)
Other malignancies (incidence, death)
Ophthalmologic disorders (cataracts)
Gastrointestinal/hepatobiliary disorders (abdominal pain, nausea)
Other adverse events impacting quality of life (vasomotor symptoms, sexual function, sleep disturbances, headaches, cognitive changes, peripheral edema)

Appendix ASearches

Appendix A-1. Search Strategies

MEDLINE Searches

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Other Database Searches

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Appendix A-2. Inclusion and Exclusion Criteria By Key Question

Table

Publication Details

Copyright

Publisher

NLM Citation