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AppendixSupplemental Table S1 PRISMA checklistSection/topic #Checklist item Reported on page # TITLE Title 1Identify the report as a systematic review, meta-analysis, or both. 1ABSTRACT Structured summary 2Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number. 3, unstructuredINTRODUCTION Rationale 3Describe the rationale for the review in the context of what is already known. 4Objectives 4Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS). 5METHODS Protocol and registration 5Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number. N.A.Eligibility criteria 6Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale. 5-6Information sources 7Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched. 5-6 and Appendix 1Search 8Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated. Appendix 1Study selection 9State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis). 5-6, Figure 1, and Appendix 1 Data collection process 10Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators. 5-6, Figure 1, and Appendix 1Data items 11List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made. 5-6, Figure 1, and Appendix 1Risk of bias in individual studies 12Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis. 6-7, Figure 2Summary measures 13State the principal summary measures (e.g., risk ratio, difference in means). 5-6Synthesis of results 14Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis. 5Risk of bias across studies 15Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies). 6-7, Figure 2Additional analyses 16Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified. N.A.RESULTS Study selection 17Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram. 6Study characteristics 18For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations. 7-9Risk of bias within studies 19Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). 6-7Results of individual studies 20For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot. N.A.Synthesis of results 21Present results of each meta-analysis done, including confidence intervals and measures of consistency. N.A.Risk of bias across studies 22Present results of any assessment of risk of bias across studies (see Item 15). 6-7, Figure 2Additional analysis 23Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]). N.A.DISCUSSION Summary of evidence 24Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers). 9-12Limitations 25Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias). 12-13Conclusions 26Provide a general interpretation of the results in the context of other evidence, and implications for future research. 13FUNDING Funding 27Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review. 14From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal.pmed1000097 Appendix 1: SEARCH STRATEGIESEmbase (Ovid): 1974 to 2017 November 30Date searched: 1.12.171 exp breast tumor/ (463769)2 (breast$ adj5 (neoplas$ or cancer$ or tumo?r$ or metasta$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or dcis or ductal or infiltrat$ or intraductal$ or lobular or medullary)).ti,ab,ot,hw. (531644)3 (mammar$ adj5 (neoplas$ or cancer$ or tumo?r$ or metasta$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or dcis or ductal or infiltrat$ or intraductal$ or lobular or medullary)).ti,ab,ot,hw. (40034)4 or/1-3 (545595)5 BRCA1 protein/ (14048)6 BRCA2 protein/ (10148)7 (BRCA or gBRCA or BRCA1 or BRCA2 or BRCAI or BRCAII or BRCC or BRCC1 or BRCCI or BRCC2 or BRCCII or BROVCA or BROVCA1 or BROVCAI or BROVCA2 or BROVCAII or "BR/OVCA" or "BR/OVCA1" or "BR/OVCAI" or "BR/OVCA2" or "BR/OVCAII" or "BRCA1/2").ti,ab,ot,hw. (29506)8 (Familial or "family history" or heredit$ or inherit$ or predispo$ or susceptib$).ti,ab,ot,hw. (1259663)9 exp genetic predisposition to disease/ (121699)10 Gene mutation/ (363425)11 (genetic or gene or genes).ti,ab,ot,hw. (3724768)12 5 or 6 or 7 or 8 or 9 or 10 or 11 (4410577)13 4 and 12 (144186)14 Productivity/ (34157)15 Absenteeism/ (16091)16 Caregiver Burden/ (5886)17 Caregiver/ (61150)18 Work Disability/ (4643)19 ((human$ or social$ or societ$ or work$ or employe$ or business$ or communit$ or famil$ or carer$ or caregiver$) adj3 (burden$ or consequenc$ or impact$ or problem$ or productivity or sickness or impairment$)).ti,ab,ot,hw. (139384)20 ((long standing or longstanding or long term or longterm or permanent or employee$) adj2 (absence$ or absent$ or ill$ or sick$ or disab$)).ti,ab,ot,hw. (12347)21 (llsi or ((emergenc$ or domestic$ or famil$ or carer$ or caregiver$) adj3 leave$)).ti,ab,ot. (880)22 (burden adj2 (illness$ or disease$ or sickness$)).ti,ab,ot,hw. (29249)23 ((allowance or status or long-term or pension$ or benefit$) adj2 (disab$ or incapacit$)).ti,ab,ot,hw. (20539)24 ((unable or inability or incapacit$ or incapab$) adj3 work).ti,ab,ot,hw. (2370)25 ((resource$ or fund$) adj2 (use$ or utili?ation)).ti,ab,ot,hw. (37496)26 ((health or healthcare) adj2 (resource$ or fund$)).ti,ab,ot,hw. (33007)27 ("length of stay" or "duration of stay" or "extended stay" or "prolonged stay").ti,ab,ot,hw. (156901)28 ((ambulatory or ambulance or hospital or A&E or emergency) adj2 (attention$ or trip or trips or visit$ or stay$ or admission$ or admitted or transport$)).ti,ab,ot,hw. (330785)29 ((GP or general practitioner$ or doctor$ or clinician$ or specialist$ or physician$) adj2 (appointment$ or attention$ or trip or trips or visit$)).ti,ab,ot,hw. (16787)30 (in-patient stay$ or inpatient stay$).ti,ab,ot,hw. (4217)31 or/14-30 (774678)32 health-economics/ (35592)33 exp economic evaluation/ (269911)34 exp health care cost/ (259269)35 exp pharmacoeconomics/ (189712)36 (econom$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$).ti,ab. (861626)37 (expenditure$ not energy).ti,ab. (33390)38 (value adj2 money).ti,ab. (2017)39 budget$.ti,ab. (32430)40 or/32-39 (1201307)41 ((metabolic adj cost) or (energy adj cost) or (energy adj expenditure)).ti,ab. (30910)42 40 not 41 (1195454)43 treatment duration/ (184231)44 exp drug dose/ (566163)45 ((treatment$ or therapeutic or therapy or therapies) adj3 (pattern$ or trend$ or utili$ or management or prevalence or initiat$ or duration or distribution$ or discontin$ or coverage or variety or selection or spread or practice or convention)).ti,ab,ot. (335152)46 ((medication$ or medicating or drug or drugs or prescrip$ or prescrib$) adj3 (pattern$ or trend$ or utili$ or management or prevalence or initiat$ or duration or distribution$ or discontin$ or coverage or variety or selection or spread or practice or convention)).ti,ab,ot. (115019)47 or/43-45 (984561)48 incidence/ (295180)49 standardized incidence ratio/ (2235)50 Prevalence/ (568914)51 standardized mortality ratio/ (2172)52 demography/ (183468)53 epidemiological data/ (29932)54 mortality/ (688917)55 disease progression/ (245423)56 disease activity/ (70162)57 morbidity/ (298266)58 (occurrence$ or incidence$ or prevalence$ or episode$ or mortalit$ or morbidit$ or epidemiolog$ or demograph$).ti,ab,ot. (3441582)59 or/48-58 (4132025)60 or/31,42,47,59 (6093169)61 13 and 60 (32302)62 animal/ (1820404)63 animal experiment/ (2184261)64 (rat or rats or mouse or mice or murine or rodent or rodents or hamster or hamsters or pig or pigs or porcine or rabbit or rabbits or animal or animals or dogs or dog or cats or cow or bovine or sheep or ovine or monkey or monkeys).ti,ab,ot,hw. (6680449)65 or/62-64 (6680449)66 exp human/ (19265608)67 human experiment/ (399595)68 or/66-67 (19267146)69 65 not (65 and 68) (5204339)70 (letter or editorial or note).pt. (2255258)71 61 not (69 or 70) (29487)72 limit 71 to yr="2012 -Current" (15079)73 conference$.pt,st,so. (3594337)74 72 and 73 (5544)75 72 not 73 (9535)Medline (Ovid): 1946 to November Week 4 2017Date searched: 1.12.171 exp breast neoplasms/ or Carcinoma, Ductal, Breast/ (279375)2 exp breast/ (44903)3 exp neoplasms/ (3234699)4 2 and 3 (26145)5 (breast$ adj5 (neoplasm$ or cancer$ or tumo?r$ or metasta$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or dcis or ductal or infiltrat$ or intraductal$ or lobular or medullary)).ti,ab,ot,hw. (337194)6 (mammar$ adj5 (neoplas$ or cancer$ or tumo?r$ or metasta$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or dcis or ductal or infiltrat$ or intraductal$ or lobular or medullary)).ti,ab,ot,hw. (41298)7 1 or 4 or 5 or 6 (360533)8 genes, brca1/ or genes, brca2/ (6459)9 brca1 protein/ or brca2 protein/ (6900)10 (BRCA or gBRCA or BRCA1 or BRCA2 or BRCAI or BRCAII or BRCC or BRCC1 or BRCCI or BRCC2 or BRCCII or BROVCA or BROVCA1 or BROVCAI or BROVCA2 or BROVCAII or "BR/OVCA" or "BR/OVCA1" or "BR/OVCAI" or "BR/OVCA2" or "BR/OVCAII" or "BRCA1/2").ti,ab,ot,hw. (16712)11 (Familial or "family history" or heredit$ or inherit$ or predispo$ or susceptib$).ti,ab,ot,hw. (808247)12 exp Genetic Predisposition to Disease/ (132716)13 (genetic or gene or genes).ti,ab,ot,hw. (2901259)14 or/8-13 (3336828)15 7 and 14 (85498)16 absenteeism/ (8858)17 caregivers/ (31396)18 ((human$ or Social or societ$ or work$ or employe$ or business$ or communit$ or famil$ or carer$ or caregiver$) adj3 (Burden$ or Consequenc$ or impact$ or problem$ or productivity or sickness or impairment$)).ti,ab,ot,hw. (92015)19 ((long standing or longstanding or long term or longterm or permanent or employee$) adj2 (absence$ or absent$ or ill$ or sick$ or disab$ or diseas$)).ti,ab,ot,hw. (16373)20 (llsi or ((emergenc$ or domestic$ or famil$ or carer$ or caregiver$) adj3 leave$)).ti,ab,ot,hw. (874)21 (burden adj2 (illness$ or disease$ or sickness$)).ti,ab,ot,hw. (16901)22 ((allowance or status or long-term or pension$ or benefit$) adj2 (disab$ or incapacit$)).ti,ab,ot,hw. (10078)23 ((unable or inability or incapacit$ or incapab$) adj3 work).ti,ab,ot,hw. (1608)24 ((resource$ or fund$) adj2 (use$ or utilis?ation)).ti,ab,ot,hw. (16817)25 ("length of stay" or "duration of stay" or "extended stay" or "prolonged stay").ti,ab,ot,hw. (100951)26 ((health or healthcare) adj2 (resource$ or fund$)).ti,ab,ot,hw. (31992)27 ((ambulatory or ambulance or hospital or A&E or emergency) adj2 (attention$ or trip or trips or visit$ or stay$ or admission$ or admitted or transport$)).ti,ab,ot,hw. (129020)28 ((GP or general practitioner$ or doctor$ or clinician$ or specialist$ or physician$) adj2 (appointment$ or attention or trip or trips or visit$)).ti,ab,ot,hw. (10600)29 (in-patient stay$ or inpatient stay$).ti,ab,ot,hw. (2113)30 or/16-29 (406872)31 economics/ (27492)32 exp "costs and cost analysis"/ (224937)33 economics, dental/ (1904)34 exp "economics, hospital"/ (23587)35 economics, medical/ (9205)36 economics, nursing/ (4019)37 economics, pharmaceutical/ (2997)38 (econom$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$).ti,ab. (593392)39 (expenditure$ not energy).ti,ab. (23035)40 (value adj1 money).ti,ab. (30)41 budget$.ti,ab. (22086)42 or/31-41 (733414)43 ((energy adj cost) or (metabolic adj cost) or (energy adj expenditure)).ti,ab. (24084)44 42 not 43 (728376)45 ((treatment$ or therapeutic or therapy or therapies) adj3 (pattern$ or trend$ or utili$ or management or prevalence or initiat$ or duration or distribution$ or discontin$ or coverage or variety or selection or spread or practice or convention)).ti,ab,ot. (204894)46 ((medication$ or medicating or drug or drugs or prescrip$ or prescrib$) adj3 (pattern$ or trend$ or utili$ or management or prevalence or initiat$ or duration or distribution$ or discontin$ or coverage or variety or selection or spread or practice or convention)).ti,ab,ot. (70936)47 45 or 46 (266896)48 morbidity/ or incidence/ or prevalence/ or mortality/ (549771)49 Demography/ (61201)50 Epidemiology/ (12480)51 disease progression/ (147969)52 (occurrence$ or incidence$ or prevalence$ or episode$ or mortalit$ or morbidit$ or epidemiolog$ or demograph$).ti,ab,ot. (2379758)53 or/48-52 (2674953)54 or/30,44,47,53 (3618706)55 15 and 54 (15266)56 animals/ not (animals/ and humans/) (4708037)57 (letter or editorial or historical article).pt. (1751143)58 55 not (56 or 57) (14127)59 limit 58 to yr="2012 -Current" (5380)Ovid MEDLINE(R) Epub Ahead of Print: November 30, 2017Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations: November 30, 2017Ovid MEDLINE(R) Daily Update: November 22, 2017Date searched: 1.12.171 exp breast neoplasms/ or Carcinoma, Ductal, Breast/ (119)2 exp breast/ (15)3 exp neoplasms/ (1099)4 2 and 3 (9)5 (breast$ adj5 (neoplasm$ or cancer$ or tumo?r$ or metasta$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or dcis or ductal or infiltrat$ or intraductal$ or lobular or medullary)).ti,ab,ot,hw. (34522)6 (mammar$ adj5 (neoplas$ or cancer$ or tumo?r$ or metasta$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or dcis or ductal or infiltrat$ or intraductal$ or lobular or medullary)).ti,ab,ot,hw. (1712)7 1 or 4 or 5 or 6 (35312)8 genes, brca1/ or genes, brca2/ (3)9 brca1 protein/ or brca2 protein/ (3)10 (BRCA or gBRCA or BRCA1 or BRCA2 or BRCAI or BRCAII or BRCC or BRCC1 or BRCCI or BRCC2 or BRCCII or BROVCA or BROVCA1 or BROVCAI or BROVCA2 or BROVCAII or "BR/OVCA" or "BR/OVCA1" or "BR/OVCAI" or "BR/OVCA2" or "BR/OVCAII" or "BRCA1/2").ti,ab,ot,hw. (2011)11 (Familial or "family history" or heredit$ or inherit$ or predispo$ or susceptib$).ti,ab,ot,hw. (76908)12 exp Genetic Predisposition to Disease/ (18)13 (genetic or gene or genes).ti,ab,ot,hw. (221041)14 or/8-13 (272252)15 7 and 14 (7262)16 absenteeism/ (0)17 caregivers/ (5)18 ((human$ or Social or societ$ or work$ or employe$ or business$ or communit$ or famil$ or carer$ or caregiver$) adj3 (Burden$ or Consequenc$ or impact$ or problem$ or productivity or sickness or impairment$)).ti,ab,ot,hw. (14132)19 ((long standing or longstanding or long term or longterm or permanent or employee$) adj2 (absence$ or absent$ or ill$ or sick$ or disab$ or diseas$)).ti,ab,ot,hw. (1930)20 (llsi or ((emergenc$ or domestic$ or famil$ or carer$ or caregiver$) adj3 leave$)).ti,ab,ot,hw. (103)21 (burden adj2 (illness$ or disease$ or sickness$)).ti,ab,ot,hw. (3403)22 ((allowance or status or long-term or pension$ or benefit$) adj2 (disab$ or incapacit$)).ti,ab,ot,hw. (1472)23 ((unable or inability or incapacit$ or incapab$) adj3 work).ti,ab,ot,hw. (135)24 ((resource$ or fund$) adj2 (use$ or utilis?ation)).ti,ab,ot,hw. (2846)25 ("length of stay" or "duration of stay" or "extended stay" or "prolonged stay").ti,ab,ot,hw. (6572)26 ((health or healthcare) adj2 (resource$ or fund$)).ti,ab,ot,hw. (3652)27 ((ambulatory or ambulance or hospital or A&E or emergency) adj2 (attention$ or trip or trips or visit$ or stay$ or admission$ or admitted or transport$)).ti,ab,ot,hw. (17415)28 ((GP or general practitioner$ or doctor$ or clinician$ or specialist$ or physician$) adj2 (appointment$ or attention or trip or trips or visit$)).ti,ab,ot,hw. (1316)29 (in-patient stay$ or inpatient stay$).ti,ab,ot,hw. (299)30 or/16-29 (49021)31 economics/ (2)32 exp "costs and cost analysis"/ (31)33 economics, dental/ (1)34 exp "economics, hospital"/ (1)35 economics, medical/ (0)36 economics, nursing/ (0)37 economics, pharmaceutical/ (6)38 (econom$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$).ti,ab. (109604)39 (expenditure$ not energy).ti,ab. (3211)40 (value adj1 money).ti,ab. (4)41 budget$.ti,ab. (4261)42 or/31-41 (113872)43 ((energy adj cost) or (metabolic adj cost) or (energy adj expenditure)).ti,ab. (2999)44 42 not 43 (113025)45 ((treatment$ or therapeutic or therapy or therapies) adj3 (pattern$ or trend$ or utili$ or management or prevalence or initiat$ or duration or distribution$ or discontin$ or coverage or variety or selection or spread or practice or convention)).ti,ab,ot. (28516)46 ((medication$ or medicating or drug or drugs or prescrip$ or prescrib$) adj3 (pattern$ or trend$ or utili$ or management or prevalence or initiat$ or duration or distribution$ or discontin$ or coverage or variety or selection or spread or practice or convention)).ti,ab,ot. (9515)47 45 or 46 (36746)48 morbidity/ or incidence/ or prevalence/ or mortality/ (51)49 Demography/ (5)50 Epidemiology/ (51)51 disease progression/ (29)52 (occurrence$ or incidence$ or prevalence$ or episode$ or mortalit$ or morbidit$ or epidemiolog$ or demograph$).ti,ab,ot. (296262)53 or/48-52 (296300)54 or/30,44,47,53 (437534)55 15 and 54 (1418)56 animals/ not (animals/ and humans/) (457)57 (letter or editorial or historical article).pt. (93449)58 55 not (56 or 57) (1412)59 limit 58 to yr="2012 -Current" (1080)CDSR (Wiley): Issue 11 of 12, November 2017DARE (Wiley): Issue 2 of 4, April 2015HTA Database (Wiley): Issue 4 of 4, October 2016NHS EED (Wiley): Issue 2 of 4, April 2015Searched: 30.11.17#1MeSH descriptor: [Breast Neoplasms] explode all trees10474#2MeSH descriptor: [Breast] explode all trees734#3MeSH descriptor: [Neoplasms] explode all trees63175#4#2 and #3 335#5((breast) near/5 (neoplasm* or cancer* or tumo?r* or metasta* or carcinoma* or adenocarcinoma* or sarcoma* or dcis or ductal or infiltrat* or intraductal* or lobular or medullary)):ti,ab,kw 26077#6((mammar*) near/5 (neoplasm* or cancer* or tumo?r* or metasta* or carcinoma* or adenocarcinoma* or sarcoma* or dcis or ductal or infiltrat* or intraductal* or lobular or medullary)):ti,ab,kw 204#7#1 or #4 or #5 or #6 26142#8MeSH descriptor: [Genes, BRCA1] this term only105#9MeSH descriptor: [Genes, BRCA2] this term only79#10MeSH descriptor: [BRCA1 Protein] explode all trees59#11MeSH descriptor: [BRCA2 Protein] explode all trees50#12(BRCA or gBRCA or BRCA1 or BRCA2 or BRCAI or BRCAII or BRCC or BRCC1 or BRCCI or BRCC2 or BRCCII or BROVCA or BROVCA1 or BROVCAI or BROVCA2 or BROVCAII or "BR/OVCA" or "BR/OVCA1" or "BR/OVCAI" or "BR/OVCA2" or "BR/OVCAII" or "BRCA1/2") 696#13(Familial or "family history" or heredit* or inherit* or predispo* or susceptib*) 23412#14MeSH descriptor: [Genetic Predisposition to Disease] explode all trees1718#15(genetic or gene or genes) 33930#16#8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 50043#17#7 and #16 Publication Year from 2012 to 20172002CDSR = 50DARE = 61CENTRAL = 1825Method Studies = 0HTA = 33NHS EED = 32Cochrane Groups = 1CINAHL (EBSCO): 2012/01/02 - 2017/11/11Searched 30.11.17S1breast neoplasms43,965S2MH breast2,342S3MH neoplasms39,982S4S2 OR S342,300S5TI ((breast) N5 (neoplasm* or cancer* or tumo?r* or metasta* or carcinoma* or adenocarcinoma* or sarcoma* or dcis or ductal or infiltrat* or intraductal* or lobular or medullary) 28,491S6AB ((breast) N5 (neoplasm* or cancer* or tumo?r* or metasta* or carcinoma* or adenocarcinoma* or sarcoma* or dcis or ductal or infiltrat* or intraductal* or lobular or medullary)24,612S7TI ((mammar*) N5 (neoplasm* or cancer* or tumo?r* or metasta* or carcinoma* or adenocarcinoma* or sarcoma* or dcis or ductal or infiltrat* or intraductal* or lobular or medullary)107S8AB ((mammar*) N5 (neoplasm* or cancer* or tumo?r* or metasta* or carcinoma* or adenocarcinoma* or sarcoma* or dcis or ductal or infiltrat* or intraductal* or lobular or medullary)247S9S1 OR S4 OR S5 OR S6 OR S7 OR S8 89,618S10(MH "Hereditary Breast and Ovarian Cancer Syndrome") OR (MH "Genes, BRCA")1,140S11TI BRCA or gBRCA or BRCA1 or BRCA2 or BRCAI or BRCAII or BRCC or BRCC1 or BRCCI or BRCC2 or BRCCII or BROVCA or BROVCA1 or BROVCAI or BROVCA2 or BROVCAII or "BR/OVCA" or "BR/OVCA1" or "BR/OVCAI" or "BR/OVCA2" or "BR/OVCAII" or "BRCA1/2" 1,001S12AB BRCA or gBRCA or BRCA1 or BRCA2 or BRCAI or BRCAII or BRCC or BRCC1 or BRCCI or BRCC2 or BRCCII or BROVCA or BROVCA1 or BROVCAI or BROVCA2 or BROVCAII or "BR/OVCA" or "BR/OVCA1" or "BR/OVCAI" or "BR/OVCA2" or "BR/OVCAII" or "BRCA1/2" 1,093S13TI Familial or "family history" or heredit* or inherit* or predispo* or susceptib*9,954S14AB Familial or "family history" or heredit* or inherit* or predispo* or susceptib* 39,309S15(MH "Polymorphism, Genetic")10,439S16TI genetic or gene or genes23,228S17AB genetic or gene or genes52,437S18S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S1797,506S19S9 AND S187,006S20S9 AND S18Limiters - Published Date: 20120101-20171231 2,405EconLit (EBSCO): 1990/06/01-2017/10/01Searched: 30.11.17S1breast neoplasms 3S2breast396S3neoplasms104S4S2 OR S3485S5TI ((breast) N5 (neoplasm* or cancer* or tumo?r* or metasta* or carcinoma* or adenocarcinoma* or sarcoma* or dcis or ductal or infiltrat* or intraductal* or lobular or medullary) 150S6AB ((breast) N5 (neoplasm* or cancer* or tumo?r* or metasta* or carcinoma* or adenocarcinoma* or sarcoma* or dcis or ductal or infiltrat* or intraductal* or lobular or medullary) 241S7TI ((mammar*) N5 (neoplasm* or cancer* or tumo?r* or metasta* or carcinoma* or adenocarcinoma* or sarcoma* or dcis or ductal or infiltrat* or intraductal* or lobular or medullary) 1S8AB ((mammar*) N5 (neoplasm* or cancer* or tumo?r* or metasta* or carcinoma* or adenocarcinoma* or sarcoma* or dcis or ductal or infiltrat* or intraductal* or lobular or medullary) 1S9S1 OR S4 OR S5 OR S6 OR S7 OR S8485S10(MH "Hereditary Breast and Ovarian Cancer Syndrome") OR (MH "Genes, BRCA") 0S11TI BRCA or gBRCA or BRCA1 or BRCA2 or BRCAI or BRCAII or BRCC or BRCC1 or BRCCI or BRCC2 or BRCCII or BROVCA or BROVCA1 or BROVCAI or BROVCA2 or BROVCAII or "BR/OVCA" or "BR/OVCA1" or "BR/OVCAI" or "BR/OVCA2" or "BR/OVCAII" or "BRCA1/2" 7S12AB BRCA or gBRCA or BRCA1 or BRCA2 or BRCAI or BRCAII or BRCC or BRCC1 or BRCCI or BRCC2 or BRCCII or BROVCA or BROVCA1 or BROVCAI or BROVCA2 or BROVCAII or "BR/OVCA" or "BR/OVCA1" or "BR/OVCAI" or "BR/OVCA2" or "BR/OVCAII" or "BRCA1/2" 12S13TI Familial or "family history" or heredit* or inherit* or predispo* or susceptib* 700S14AB Familial or "family history" or heredit* or inherit* or predispo* or susceptib* 4,298S15(MH "Polymorphism, Genetic")12S16TI genetic or gene or genes1,260S17AB genetic or gene or genes2,796S18S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 7,844S19S9 AND S18 55S20S9 AND S18 19Northern Light Life Sciences Conference Abstracts (Ovid): 2014-2017 Week 47Searched: 7.12.171 (breast$ adj5 (neoplas$ or cancer$ or tumo?r$ or metasta$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or dcis or ductal or infiltrat$ or intraductal$ or lobular or medullary)).ti,ab. (59371)2 (mammar$ adj5 (neoplas$ or cancer$ or tumo?r$ or metasta$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or dcis or ductal or infiltrat$ or intraductal$ or lobular or medullary)).ti,ab. (2646)3 1 or 2 (60193)4 (BRCA or gBRCA or BRCA1 or BRCA2 or BRCAI or BRCAII or BRCC or BRCC1 or BRCCI or BRCC2 or BRCCII or BROVCA or BROVCA1 or BROVCAI or BROVCA2 or BROVCAII or "BR/OVCA" or "BR/OVCA1" or "BR/OVCAI" or "BR/OVCA2" or "BR/OVCAII" or "BRCA1/2").ti,ab. (4304)5 (Familial or "family history" or heredit$ or inherit$ or predispo$ or susceptib$).ti,ab. (79231)6 (genetic or gene or genes).ti,ab. (246171)7 4 or 5 or 6 (294579)8 3 and 7 (12795)9 ((human$ or social$ or societ$ or work$ or employe$ or business$ or communit$ or famil$ or carer$ or caregiver$) adj3 (burden$ or consequenc$ or impact$ or problem$ or productivity or sickness or impairment$)).ti,ab. (12359)10 ((long standing or longstanding or long term or longterm or permanent or employee$) adj2 (absence$ or absent$ or ill$ or sick$ or disab$)).ti,ab. (950)11 (llsi or ((emergenc$ or domestic$ or famil$ or carer$ or caregiver$) adj3 leave$)).ti,ab. (50)12 (burden adj2 (illness$ or disease$ or sickness$)).ti,ab. (4200)13 ((allowance or status or long-term or pension$ or benefit$) adj2 (disab$ or incapacit$)).ti,ab. (1128)14 ((unable or inability or incapacit$ or incapab$) adj3 work).ti,ab. (114)15 ((resource$ or fund$) adj2 (use$ or utili?ation)).ti,ab. (5409)16 ((health or healthcare) adj2 (resource$ or fund$)).ti,ab. (4489)17 ("length of stay" or "duration of stay" or "extended stay" or "prolonged stay").ti,ab. (6714)18 ((ambulatory or ambulance or hospital or A&E or emergency) adj2 (attention$ or trip or trips or visit$ or stay$ or admission$ or admitted or transport$)).ti,ab. (13941)19 ((GP or general practitioner$ or doctor$ or clinician$ or specialist$ or physician$) adj2 (appointment$ or attention$ or trip or trips or visit$)).ti,ab. (1005)20 (in-patient stay$ or inpatient stay$).ti,ab. (477)21 (econom$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$).ti,ab. (100814)22 (expenditure$ not energy).ti,ab. (2929)23 (value adj2 money).ti,ab. (268)24 budget$.ti,ab. (3532)25 ((treatment$ or therapeutic or therapy or therapies) adj3 (pattern$ or trend$ or utili$ or management or prevalence or initiat$ or duration or distribution$ or discontin$ or coverage or variety or selection or spread or practice or convention)).ti,ab. (29859)26 ((medication$ or medicating or drug or drugs or prescrip$ or prescrib$) adj3 (pattern$ or trend$ or utili$ or management or prevalence or initiat$ or duration or distribution$ or discontin$ or coverage or variety or selection or spread or practice or convention)).ti,ab. (10198)27 (occurrence$ or incidence$ or prevalence$ or episode$ or mortalit$ or morbidit$ or epidemiolog$ or demograph$).ti,ab. (290234)28 or/9-27 (433166)29 8 and 28 (2084)30 limit 29 to yr="2016 -Current" (253)CEA Registry (Internet): up to 30 Nov 2017Searched 30.11.172012-CurrentSearch termsResultsBRCA6BRCC0gBRCA0BROVCA0Total6ScHARR Health Utilities Database (ScHARRHUD)(Internet): up to 30 Nov 2017Searched 7.12.172012-2017Search termsResultsBRCA0BRCC0gBRCA0BROVCA0Breast7Total7NCCN 21st Annual Conference ()Searched 8.12.17Search termsHitsBC5BRCA0/1BRCC0Total5Additional Conference HandsearchingESMO 2017 Abstract book: Antonio BC Symposium 2016 Abstract book: 2016 Abstracts from: 2 FURTHER DETAILS OF PREVALENCE RESULTSCountryStudy ID Germline reportedDeleterious reportedSelectionHormoneReceptor statusBreast cancer stageNo. at risk of mutation% BRCA1/2% BRCA1% BRCA2% BRCA1 and 2USABayraktar, 2013 ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><Author>Bayraktar</Author><Year>2013</Year><RecNum>1</RecNum><DisplayText><style face="superscript">1</style></DisplayText><record><rec-number>1</rec-number><foreign-keys><key app="EN" db-id="fe5d02darx2vdyezdr45w2fcx00ad5a5s5rr" timestamp="1549931379">1</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bayraktar, S.</author><author>Gutierrez-Barrera, A. M.</author><author>Lin, H.</author><author>Elsayegh, N.</author><author>Tasbas, T.</author><author>Litton, J. K.</author><author>Ibrahim, N. K.</author><author>Morrow, P. K.</author><author>Green, M.</author><author>Valero, V.</author><author>Booser, D. J.</author><author>Hortobagyi, G. N.</author><author>Arun, B. K.</author></authors></contributors><titles><title>Outcome of metastatic breast cancer in selected women with or without deleterious BRCA mutations</title><secondary-title>Clin Exp Metastasis</secondary-title></titles><periodical><full-title>Clin Exp Metastasis</full-title></periodical><pages>631-42</pages><volume>30</volume><number>5</number><edition>2013/02/02</edition><dates><year>2013</year></dates><urls></urls></record></Cite></EndNote>1YesdeleteriousMixedMixedMetastatic1952115.06.00.0TNBC4436.434.12.3Beck, 2017 ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><Author>Beck</Author><Year>2017</Year><RecNum>2</RecNum><DisplayText><style face="superscript">2</style></DisplayText><record><rec-number>2</rec-number><foreign-keys><key app="EN" db-id="fe5d02darx2vdyezdr45w2fcx00ad5a5s5rr" timestamp="1549931383">2</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Beck, A.</author><author>Yuan, H.</author><author>Imperiale-Hagerman, P.</author><author>Shipley, K.</author><author>Erdahl, L.</author><author>Sugg, S.</author><author>Weigel, R.</author><author>Lizarraga, I.</author></authors></contributors><titles><title>Adhering to the guidelines: rates of BRCA mutation using NCCN genetic testing criteria</title><secondary-title>Annals of Surgical Oncology</secondary-title></titles><periodical><full-title>Annals of Surgical Oncology</full-title></periodical><pages>257048</pages><volume>24</volume><number>2</number><dates><year>2017</year></dates><urls></urls></record></Cite></EndNote>2NoYoung (<50 years) age at diagnosisNR/unclear19910.5NRNRNRBiskupiak, 2017 ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><Author>Biskupiak</Author><Year>2017</Year><RecNum>3</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="fe5d02darx2vdyezdr45w2fcx00ad5a5s5rr" timestamp="1549931391">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Biskupiak, J. E.</author><author>Telford, C.</author><author>Yoo, M.</author><author>Unni, S. K.</author><author>Ye, X.</author><author>Deka, R.</author><author>Brixner, D. L.</author><author>Stenehjem, D. D.</author></authors></contributors><titles><title>Evaluation of women with BRCA mutations and breast cancer tested at an NCI designated comprehensive cancer center: A cost of illness estimation</title><secondary-title>Cancer Research</secondary-title></titles><periodical><full-title>Cancer Research</full-title></periodical><dates><year>2017</year></dates><urls></urls></record></Cite></EndNote>3NR/unclearNR/unclearMixedInvasive81616.4Buys, 2017 ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><Author>Buys</Author><Year>2017</Year><RecNum>4</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>4</rec-number><foreign-keys><key app="EN" db-id="fe5d02darx2vdyezdr45w2fcx00ad5a5s5rr" timestamp="1549931397">4</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Buys, S. S.</author><author>Sandbach, J. F.</author><author>Gammon, A.</author><author>Patel, G.</author><author>Kidd, J.</author><author>Brown, K. L.</author><author>Sharma, L.</author><author>Saam, J.</author><author>Lancaster, J.</author><author>Daly, M. B.</author></authors></contributors><titles><title>A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes</title><secondary-title>Cancer</secondary-title></titles><periodical><full-title>Cancer</full-title></periodical><pages>1721-1730</pages><volume>123</volume><number>10</number><dates><year>2017</year></dates><urls></urls></record></Cite></EndNote>4pathogenicMixedNR/unclear354094.62.32.30.0TNBC47979.87.22.6Couch, 2015PEVuZE5vdGU+PENpdGUgRXhjbHVkZUF1dGg9IjEiIEV4Y2x1ZGVZZWFyPSIxIj48QXV0aG9yPkNv

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T.</author><author>Pisano, M.</author><author>Tanda, F.</author><author>Cossu, A.</author><author>Palmieri, G.</author></authors></contributors><titles><title>Triple-negative breast cancer frequency and type of BRCA mutation: clues from Sardinia</title><secondary-title>Oncology Letters</secondary-title></titles><periodical><full-title>Oncology Letters</full-title></periodical><pages>948-952</pages><volume>7</volume><number>4</number><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>59YesdeleteriousUnselectedMixed7262.91.01.90.0TNBC4914.3NRNRNRSouth KoreaHan, 2013 ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><Author>Han</Author><Year>2013</Year><RecNum>60</RecNum><DisplayText><style face="superscript">60</style></DisplayText><record><rec-number>60</rec-number><foreign-keys><key app="EN" db-id="fe5d02darx2vdyezdr45w2fcx00ad5a5s5rr" timestamp="1549931735">60</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Han, S. 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Y.</author><author>Yoon, K. A.</author><author>Lee, K. S.</author><author>Cho, E. H.</author><author>Lim, M. C.</author><author>Yang, M. J.</author><author>Park, S. J.</author><author>Lee, M. H.</author><author>Lee, S. Y.</author><author>Chang, Y. J.</author><author>Lee, D. O.</author><author>Kong, S. Y.</author><author>Lee, E. S.</author></authors></contributors><titles><title>Characteristics of BRCA1/2 mutations carriers including large genomic rearrangements in high risk breast cancer patients</title><secondary-title>Breast Cancer Research and Treatment</secondary-title></titles><periodical><full-title>Breast Cancer Research and Treatment</full-title></periodical><pages>139-150</pages><volume>163</volume><number>1</number><dates><year>2017</year></dates><urls></urls></record></Cite></EndNote>66pathogenicFamily history of breast or ovarian cancer or diagnosis age ≤40 years with bilateral BC or BC with other primary malignancy or male BC, in accordance with the standard of National Medical Insurance Reimbursement in KoreaHR+/HER2-Mixed2529.92.47.50Mixed47813.26.36.9TNBC7629254Seong, 2014PEVuZE5vdGU+PENpdGUgRXhjbHVkZUF1dGg9IjEiIEV4Y2x1ZGVZZWFyPSIxIj48QXV0aG9yPlNl

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ADDIN EN.CITE.DATA 67Yesclinically significantFamily history, femaleMixed22136.718.118.6TNBC4259.547.611.9Sohn, 2016 ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><Author>Sohn</Author><Year>2016</Year><RecNum>68</RecNum><DisplayText><style face="superscript">68</style></DisplayText><record><rec-number>68</rec-number><foreign-keys><key app="EN" db-id="fe5d02darx2vdyezdr45w2fcx00ad5a5s5rr" timestamp="1549931788">68</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sohn, J. Y.</author><author>Park, B.</author><author>Yoon, K. A.</author><author>Park, S. J.</author><author>Lee, M. H.</author><author>Cho, E. H.</author><author>Lee, K. S.</author><author>Lim, M. C.</author><author>Kong, S. Y.</author><author>Lee, E. S.</author></authors></contributors><titles><title>Prevalence of BRCA1 and BRCA2 small mutation and large genomic rearrangements in breast cancer patients visiting a genetic counseling clinic</title><secondary-title>Cancer Research</secondary-title></titles><periodical><full-title>Cancer Research</full-title></periodical><pages>3474</pages><volume>76</volume><number>14</number><dates><year>2016</year></dates><urls></urls></record></Cite></EndNote>68NoNR/unclearUnselectedNR/unclearNR/unclear35814.8NRNRNRSon, 2012 ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><Author>Son</Author><Year>2012</Year><RecNum>69</RecNum><DisplayText><style face="superscript">69</style></DisplayText><record><rec-number>69</rec-number><foreign-keys><key app="EN" db-id="fe5d02darx2vdyezdr45w2fcx00ad5a5s5rr" timestamp="1549931793">69</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Son, B. H.</author><author>Ahn, S. H.</author><author>Kim, S. W.</author><author>Kang, E.</author><author>Park, S. K.</author><author>Lee, M. H.</author><author>Noh, W. C.</author><author>Kim, L. S.</author><author>Jung, Y.</author><author>Kim, K. S.</author><author>Noh, D. Y.</author><author>Moon, B. I.</author><author>Suh, Y. J.</author><author>Lee, J. E.</author><author>Choi, D. H.</author><author>Kim, S. Y.</author><author>Jung, S. H.</author><author>Yom, C. K.</author><author>Lee, H.</author><author>Yang, J. H.</author></authors></contributors><titles><title>Prevalence of BRCA1 and BRCA2 mutations in non-familial breast cancer patients with high risks in Korea: the Korean Hereditary Breast Cancer (KOHBRA) Study</title><secondary-title>Breast Cancer Research and Treatment</secondary-title></titles><periodical><full-title>Breast Cancer Research and Treatment</full-title></periodical><pages>1143-1152</pages><volume>133</volume><number>3</number><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>69High risk (early onset BC defined as diagnosis age ≤ 40, bilateral BC, personal history of breast and ovarian cancer, male BC, or cancer of multiple organs that include breast)7588.63.35.30.13Yoon, 2017 ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><Author>Yoon</Author><Year>2017</Year><RecNum>70</RecNum><DisplayText><style face="superscript">70</style></DisplayText><record><rec-number>70</rec-number><foreign-keys><key app="EN" db-id="fe5d02darx2vdyezdr45w2fcx00ad5a5s5rr" timestamp="1549931797">70</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yoon, K. A.</author><author>Park, B.</author><author>Lee, B. I.</author><author>Yang, M. J.</author><author>Kong, S. Y.</author><author>Lee, E. S.</author></authors></contributors><titles><title>Clinically significant unclassified variants in BRCA1 and BRCA2 genes among Korean breast cancer patients</title><secondary-title>Cancer Research &amp; Treatment</secondary-title></titles><periodical><full-title>Cancer Research &amp; Treatment</full-title></periodical><pages>627-634</pages><volume>49</volume><number>3</number><dates><year>2017</year></dates><urls></urls></record></Cite></EndNote>70pathogenicMixedMixed32814.36.18.20Note: aNot fulfilling any of the following criteria: BC <40 years, bilateral BC <60 years, TNBC, BC + ovarian cancer, male BC.Abbreviations: BC, breast cancer; BRCA, BC susceptibility gene; HER2-, human epidermal growth factor receptor 2–negative; HR+, hormone receptor– positive; ID,?identification; low+ indicates 1%-9% on immunohistochemistry; NA, not applicable; NR, not reported; TNBC, triple-negative BC.Appendix 3: EXCLUDED STUDIESReasonReferencePopulationAkdeniz D, Tuncer BS, Kilic S, Sukruoglu O, Kilic L, Altundag K, et al. Distribution and frequency of BRCA gene mutations in Turkish population including Balkan Turks. Cancer Res. 2014;74(23):Abstract 43.Alemar B, Gregorio C, Artigalas O, Netto C, Ashton-Prolla P. Prevalence of BRCA1 and BRCA2 mutations in patients fulfilling HBOC criteria in South Brazil. J Clin Oncol. 2015;33(15 Suppl):e12529.Alemar B, Herzog J, Ashton-Prolla P, Weitzel J. Prevalence of Hispanic BRCA1 and BRCA2 mutations among HBOC patients from Southern Brazil reveal differences among Latin American populations. Cancer Res. 2016;76(4 Suppl):Abstract P2-09-12.Alemar B, Herzog J, Brinckmann Oliveira Netto C, Artigalas O, Schwartz IVD, Matzenbacher Bittar C, et al. Prevalence of Hispanic BRCA1 and BRCA2 mutations among hereditary breast and ovarian cancer patients from Brazil reveals differences among Latin American populations. Cancer Genet. 2016;209(9):417-422.Ancot F, Arcand SL, Nolet S, Mes-Masson AM, El Haffaf Z, Provencher DM, et al. Double heterozygotes for PALB2 and BRCA1/BRCA2 mutation carriers in French Canadian hereditary BC patients. Curr Oncol. 2014;21(2):e367.Arai M, Yokoyama S, Watanabe C, Yoshida R, Kita M, Okawa M, et al. Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan. J Hum Genet. 2017:1-11.Ashton-Prolla P, Vargas FR. Prevalence and impact of founder mutations in hereditary BC in Latin America. Genet Mol Biol. 2014;37(1 Suppl 1):234-240.Blok EJ, Bastiaannet E, van den Hout WB, Liefers GJ, Smit VTHBM, Kroep JR, et al. Systematic review of the clinical and economic value of gene expression profiles for invasive early BC available in Europe. Cancer Treat Rev. 2018;62:74-90.Caputo S, Benboudjema L, Sinilnikova O, Rouleau E, Beroud C, Lidereau R, et al. Description and analysis of genetic variants in French hereditary breast and ovarian cancer families recorded in the UMD-BRCA1/BRCA2 databases. Nucleic Acids Res. 2012;40(D1):D992-D1002.Chang Y, Near AM, Butler KM, Hoeffken A, Edwards SL, Stroup AM, et al. Economic evaluation alongside a clinical trial of telephone versus in-person genetic counseling for BRCA1/2 mutations in geographically underserved areas. J Oncol Pract. 2016;12(1):e1-e13.Collet G, Parodi N, Cassinari K, Neviere Z, Cohen F, Gasnier C, et al. Cost-effectiveness evaluation of pre-counseling telephone interviews before face-to-face genetic counseling in cancer genetics. Fam Cancer. 2017:1-7.DaCosta Byfield S, Buck PO, Blauer-Peterson C, Poston SA, DaCosta Byfield S, Buck PO, et al. ReCAP: treatment patterns and cost of care associated with initial therapy among patients diagnosed with operable early-stage human epidermal growth factor receptor 2-overexpressed BC in the United States: a real-world retrospective study. J Oncol Pract. 2016;12(2):159-167.De Bruin MA, Kwong A, Goldstein BA, Lipson JA, Ikeda DM, McPherson L, et al. BC risk factors differ between Asian and white women with BRCA1/2 mutations. Fam Cancer. 2012;11(3):429-439.Dodova R, Mitkova A, Dacheva D, Taushanova M, Valev S, Vlahova A, et al. 583: Recurrent BRCA1/2 mutations in Bulgarian patients with hereditary breast and ovarian cancer. Eur J Cancer. 2014;50(Suppl 5):S140–S140.Ellingson MS, Hart SN, Kalari KR, Suman V, Schahl KA, Dockter TJ, et al. Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive BC undergoing neoadjuvant chemotherapy. Breast Cancer Res Treat. 2015;153(2):435-443.Habak N, Ladjroud A, Benzidane N, Chikouche A, Ait Abdallah M, Bouzid K, et al. BRCA1 and BRCA2 germline mutations in Algerian familial breast and or ovarian cancer patients. Clin Chem Lab Med. 2017;55:S951.Hirotsu Y, Nakagomi H, Sakamoto I, Amemiya K, Mochizuki H, Omata M. Detection of BRCA1 and BRCA2 germline mutations in Japanese population using next-generation sequencing. Mol Gen Genomic Med. 2015;3(2):121-129.Jakub J, Peled A, Gray R, Greenup R, Kiluk J, Sacchini V, et al. Multi-institutional study of the oncologic safety of prophylactic nipple-sparing mastectomy in a BRCA population. Ann Surg Oncol. 2016;23(3 Suppl):311.Joyce D, Heneghan H, Curran C, O'Neill C, Kerin M. The economic impact of BC management. Ir J Med Sci. 2014;183(5 Suppl 1):S235.Kim RS, Peterson A, Isherwood A, Uppal H, Barlev A. Incidence of germline BRCA 1 and 2 mutated BC in the EU5. Value Health. 2016;19(7):A715.Kolben T, Hary T, Holdt LM, Schwarz TM, Goess C, Wuerstlein R, et al. Thyroid hormones and vitamin D in patients with breast cancer with mutations in BRCA1 or BRCA2 genes. Anticancer Res. 2016;36(6):3185.Konstantopoulou I, Tsitlaidou M, Fostira F, Pertesi M, Stavropoulou AV, Triantafyllidou O, et al. High prevalence of BRCA1 founder mutations in Greek breast/ovarian families. Clin Genet. 2014;85(1):36-42.Kuo WH, Lin PH, Huang AC, Chien YH, Liu TP, Lu YS, et al. Multimodel assessment of BRCA1 mutations in Taiwanese (ethnic Chinese) women with early-onset, bilateral or familial BC. J Hum Genet. 2012;57(2):130-138.Laraqui A, Uhrhammer N, Rhaffouli HE, Sekhsokh Y, Lahlou-Amine I, Bajjou T, et al. BRCA genetic screening in Middle Eastern and North African: mutational spectrum and founder BRCA1 mutation (c.798_799delTT) in North African. Dis Markers. 2015;2015:194293.Lin Y, Tang C, Chien L, Liao C. Costs and life expectancy increased among patients with breast cancer across two time periods. Value Health. 2017;20(9):A466.Luporsi E, Bronner M, Lesur A, Saint-Dizier D, Sokolowska J, Mansuy L, et al. Characteristics of the BRCA mutation profile of a population of patients with triple negative BC. Cancer Res. 2013;73(24 Suppl): Abstract P2-12-02.Lux MP, Nabieva N, Hildebrandt T, Rebscher H, Kummel S, Blohmer JU, et al. Budget impact analysis of gene expression tests to aid therapy decisions for breast cancer patients in Germany. Breast. 2018;37:89-98.Metcalfe K, Ghadirian P, Lynch HT, Snyder C, Foulkes WD, Tung N, et al. The impact of oophorectomy on survival after breast cancer in BRCA1 and BRCA2 mutation carriers. Curr Oncol. 2014;21(2):e361.Nelson HD, Pappas M, Zakher B, Mitchell JP, Okinaka-Hu L, Fu R. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the U.S. Preventive Services Task Force Recommendation. Ann Intern Med. 2014;160(4):255-266.Olson MA, Tutera S, Williams C. Implementation of genetic sequencing in breast and ovarian cancer patients: a cost analysis. Cancer Res. 2015;75(15 Suppl):Abstract 5490.Retel VP, Joore MA, Drukker CA, Bueno-De-Mesquita JM, Knauer M, Van Tinteren H, et al. Prospective cost-effectiveness analysis of genomic profiling in breast cancer. Eur J Cancer. 2013;49(18):3773-3779.Riahi A, Chabouni-Bouhamed H, Kharrat M. Prevalence of BRCA1 and BRCA2 large genomic rearrangements in Tunisian high risk breast/ovarian cancer families: implications for genetic testing. Cancer Genet. 2017;210:22-27.Ricks-Santi L, McDonald JT, Gold B, Dean M, Thompson N, Abbas M, et al. Next generation sequencing reveals high prevalence of BRCA1 and BRCA2 variants of unknown significance in early-onset BC in African American women. Ethn Dis;2017;27(2):169-178.Roberts MC, Dusetzina SB. Use and costs for tumor gene expression profiling panels in the management of BC from 2006 to 2012: implications for genomic test adoption among private payers. J Oncol Pract. 2015;11(4):273-277.Santonocito C, Scapaticci M, Guarino D, Bartolini A, Minucci A, Concolino P, et al. Identification of twenty-nine novel germline unclassified variants of BRCA1 and BRCA2 genes in 1400 Italian individuals. Breast. 2017;36:74-78.Slade I, Hanson H, George A, Kohut K, Strydom A, Wordsworth S, et al. A cost analysis of a cancer genetic service model in the UK. J Community Genet. 2016;7(3):185-czewska-Bruns J, Hempel D, Pancewicz-Janczuk B, Kazberuk D, Rozkowska E, Huzarski T, et al. Clinical features and treatment outcome in BRCA1-postive breast cancer patients n single institution analysis. Radiother Oncol. 2015;115:S646.Vaca-Paniagua F, Alvarez-Gomez RM, Fragoso-Ontiveros V, Vidal-Millan S, Herrera LA, Cantu D, et al. Full-exon pyrosequencing screening of BRCA germline mutations in Mexican women with inherited breast and ovarian cancer. PLoS One. 2012;7(5).Vietri MT, Molinari AM, De Paola ML, Cantile F, Fasano M, Cioffi M. Identification of a novel in-frame deletion in BRCA2 and analysis of variants of BRCA1/2 in Italian patients affected with hereditary breast and ovarian cancer. Clin Chem Lab Med. 2012;50(12):2171-2180.Vig HS, McCarthy AM, Liao K, Demeter MB, Fredericks T, Armstrong K. Age at diagnosis may trump family history in driving BRCA testing in a population of breast cancer patients. Cancer Epidemiol Biomark Prev. 2013;22(10):1778-1785.OutcomeCherbal F, Gaceb H, Mehemmai C, Saiah I, Bakour R, Ould-Rouis A, et al. Triple-negative breast cancer in Algerian population: Clinicopathological and molecular study. Cancer Res. 2015;75(15 Suppl):Abstract 5284.Cho JY, Cho DY, Ahn SH, Choi SY, Shin I, Park HG, et al. Large genomic rearrangement of BRCA 1 and BRCA2 genes in familial breast cancer patients in South Korea. Fam Cancer. 2014;13(2):205-211.D'Argenio V, Esposito MV, D'Aiuto M, Precone V, Cantiello P, Calabrese A, et al. BRCA1 and BRCA2 rapid germline mutations screening by next generation sequencing approach. Biochimica Clinica. 2013;37:S166.Gustavsen G, Schroeder B, Kennedy P, Pothier KC, Schnabel CA, Erlander MG. Health economic analysis of Breast Cancer Index in patients with ER+, LN- breast cancer. J Clin Oncol. 2013.Hartwig M, Janiszewska H, Bak A, Pilarska M, Heise M, Junkiert-Czarnecka A, et al. Prevalence of the BRCA1 c.68_69delAG (BIC: 185delAG) mutation in women with breast cancer from north-central Poland and a review of the literature on other regions of the country. Contemp Oncol (Pozn). 2013;17(1):34-37.Hernan I, Mane B, Borras E, de Sousa Dias M, Llort G, Yague C, et al. Two novel frameshift mutations in BRCA2 gene detected by next generation sequencing in a survey of Spanish patients of breast cancer. Clin Transl Oncol. 2015;17(7):576-580.Ho AY, Amoroso K, Wilgucki M, Vora K, Arnold BB, Powell SN, et al. Prevalence and impact of variants of uncertain significance on local therapy decision-making in newly diagnosed breast cancer patients. Int J Radiat Oncol Biol Phys. 2017;99(2):E2.Hornberger J, Michael DA, Rebecca C, Hialy RG, Tiffany MY, William JG. Clinical validity/utility, change in practice patterns, and economic implications of risk stratifiers to predict outcomes for early-stage breast cancer: a systematic review. J Natl Cancer Inst. 2012;104(14):1068-1079.Kang E, Kim D, Yom CK, Kim SW, Ahn SH, Park SK, et al. South Korean hereditary breast cancer (KOHBRA) study. Eur J Cancer. 2012;48:S77-S78.Kim R, Peterson A, Isherwood A, Uppal H, Barlev A. Incidence of germline BRCA1-and BRCA2-mutated breast cancer in the US. Cancer Res. 2017;77(4 Suppl):Abstract P5-08-28.Kim RS, Peterson A, Isherwood A, Uppal H, Barlev A. Incidence of germline BRCA 1 and 2 mutated breast cancer in the EU5. Value Health. 2016;19:A715.Ou J, Wu T, Ni D, Xu W, Chen L, Halmurat U. BRCA1 and BRCA2 deleterious mutations in 68 patients with hereditary predisposition to breast cancer among multiple ethnic groups in Xinjiang. Chin J Clin Oncol. 2012;39(20):1539-1541.Petelin L, Trainer A, Liew D, James P, Mitchell G. A systematic review of comparative effectiveness models and economic evaluations for cancer risk management strategies in brca1/2 mutation carriers. Asia Pac J Clin Oncol. 2016;12:155-156.Ragaz J, Coldman A, Fox J, Wilson KS, Shakeraneh S, Zheng Y, et al. breast cancer incidence among young women of urban China (Shanghai) and in Canada: implications for prevention. J Clin Oncol. 2014;32(15 Suppl):1576.Riahi A, Kharrat M, Ghourabi ME, Khomsi F, Gamoudi A, Lariani I, et al. Mutation spectrum and prevalence of BRCA1 and BRCA2 genes in patients with familial and early-onset breast/ovarian cancer from Tunisia. Clin Genet. 2015;87(2):155-160.Son BH, Ahn SH, Yu JH, Kim HJ, Ko BS, Cho JY, et al. Analysis of large genomic rearrangements of BRCA1/2 genes in South Korean breast cancer patients. Eur J Cancer. 2012;48:S120-S121.Torous VF, Schnitt S, Garber J, Hacker M, Poles E, Alexander B, et al. Prevalence of androgen receptor expression in triple negative breast cancers according to BRCA1 mutation status. Lab Invest. 2015;95:44A.Zhang J, Fackenthal JD, Zheng Y, Huo D, Hou N, Niu Q, et al. Recurrent BRCA1 and BRCA2 mutations in breast cancer patients of African ancestry. Breast Cancer Res Treat. 2012;134(2):889-894.Zonno KD, Kaldate RR, Arnell C, Saam J, Abbott B, Hartman AR. BRCA1/2 mutation prevalence among triple-negative breast cancer patients from a large commercial testing cohort. J Clin Oncol. 2013;(15_suppl):1544.Not relevant study designBayraktar S, Gluck S. Systemic therapy options in BRCA mutation-associated breast cancer. Breast Cancer Res Treat. 2012;135(2):355-366.Isherwood A, Duval A, Parihar N. BRCA1/2-mutated breast cancer in select EU markets: incidence, treatable populations, and potential market size for PARP inhibitors. Value Health. 2017;20(9):A468.Kohut K, D'Mello L, Bancroft EK, Thomas S, Young MA, Myhill K, et al. Implications for cancer genetics practice of pro-actively assessing family history in a General Practice cohort in North West London. Fam Cancer. 2012;11(1):107-113.Neamatzadeh H, Shiryazdi SM, Kalantar SM. BRCA1 and BRCA2 mutations in Iranian breast cancer patients: a systematic review. J Res Med Sci. 2015;20(3):284-293.Ragaz J, Coldman A, Wilson KS, Fox J, Shakeraneh S, Wong H, et al. Long-term breast cancer outcomes in Canada with special analyses of cancer care access and mortality reduction. J Clin Oncol. 2014;32(15 Suppl):1601.Rosenthal E, Moyes K, Arnell C, Evans B, Wenstrup RJ. Incidence of BRCA1 and BRCA2 non-founder mutations in patients of Ashkenazi Jewish ancestry. Breast Cancer Res Treat. 2015;149(1):223-227. Erratum in Breast Cancer Res Treat. 2015;151(1):233. Valachis A, Nearchou AD, Lind P. Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis. Breast Cancer Res Treat. 2014;144(5):443-455.BackgroundBraga TL, Portilho FL, Santos-Oliveira R. breast cancer treatment protocols: Systematic review of the last 35 years. J Anal Oncol. 2017;6(2):57-102.Cherbal F, Bakour R, Adane S, Boualga K. BRCA1 and BRCA2 germline mutation spectrum in hereditary breast/ovarian cancer families from Maghrebian countries. Breast Dis. 2013;34(1):1-8.Dutil J, Golubeva VA, Pacheco-Torres AL, Diaz-Zabala HJ, Matta JL, Monteiro AN. The spectrum of BRCA1 and BRCA2 alleles in Latin America and the Caribbean: a clinical perspective. Breast Cancer Res Treat. 2015;154(3):441-453.Forat-Yazdi M, Neamatzadeh H, Sheikhha MH, Zare-Shehneh M, Fattahi M. BRCA1 and BRCA2 common mutations in Iranian breast cancer patients: a meta analysis. Asian Pac J Cancer Prev. 2015;16(3):1219-1224.Freeman AH, Powell CB, Kutner S, Janes K. Cost savings of population based genetic testing among Ashkenazi Jewish adult females in Northern California. Gynecol Oncol. 2016;143(1):195-196.Jara L, Morales S, de Mayo T, Gonzalez-Hormazabal P, Carrasco V, Godoy R. Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations. Biol Res. 2017;50(1):35.Kang E, Kim SW. The South Korean hereditary breast cancer study: review and future perspectives. J Breast Cancer. 2013;16(3):245-253.Kim H, Choi DH. Distribution of BRCA1 and BRCA2 mutations in Asian patients with breast cancer. J Breast Cancer. 2013;16(4):357-365.Kwong A, Ng EKO, Wong CLP, Law FBF, Au T, Wong HN, et al. Identification of BRCA1/2 founder mutations in Southern Chinese breast cancer patients using gene sequencing and high resolution DNA melting analysis. PLoS One. 2012;7(9).Laraqui A, Uhrhammer N, El Rhaffouli H, Sekhsokh Y, Lahlou-Amine I, Bajjou T, et al. BRCA genetic screening in Middle Eastern and North African: Mutational spectrum and founder BRCA1 mutation (c.798-799delTT) in North African. Dis Markers. 2015;2015(194293):8.Mirza MM, McCular B, Martin MG. Therapy related myeloid and lymphoid neoplasms in BRCA mutated breast and ovarian cancer patients. Blood. 2016;128(22):5115.Nelson HD, Fu R, Goddard K, Mitchell JP, Okinaka-Hu L, Pappas M, et al. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: systematic review to update the U.S. preventive services task force recommendation. Agency for Healthcare Research Quality; 2014. . Accessed February 15, 2019.Sullivan W, Evans DG, Newman WG, Ramsden SC, Scheffer H, Payne K. Developing national guidance on genetic testing for breast cancer predisposition: the role of economic evidence? Genet Test Mol Biomarkers. 2012;16(6):580-591.Tun NM, Villani G, Ong K, Yoe L, Bo ZM. Risk of having BRCA1 mutation in high-risk women with triple-negative breast cancer: a meta-analysis. Clin Genet. 2014;85(1):43-48.Wang F, Fang Q, Ge Z, Yu N, Xu S, Fan X. Common BRCA1 and BRCA2 mutations in breast cancer families: a meta-analysis from systematic review. Mol Biol Rep. 2012;39(3):2109-2118.DuplicateSeong MW, Cho SI, Kim KH, Chung IY, Kang E, Lee JW, et al. A multi-institutional study of the prevalence of BRCA1 and BRCA2 large genomic rearrangements in familial breast cancer patients. BMC Cancer. 2014;14(1).Xiong WW, Nyin LK, Jamie A, Luccarini C, Mariapun S, Har YC, et al. Inherited mutations in BRCA1 and BRCA2 in an unselected multi-ethnic cohort of Asian breast cancer patients and healthy controls from Malaysia. Presented at: American Association for Cancer Research Annual Meeting 2017; 01-Apr-2017. American Association for Cancer Research (AACR). Available at: X, Devi B, Sung H, Guida J, Xiao Y, Garland L, et al. Prevalence and spectrum of germline rare variants in BRCA1/2 and PALB2 among breast cancer cases in Sarawak, Malaysia. Presented at: American Association for Cancer Research Annual Meeting 2017; 01-Apr-2017. American Association for Cancer Research (AACR). Available at: (Other country/or not available)Elsakov P, Ostapenko V, Luksyte A, Smailyte G. Management and 5-year survival of BRCA1-associated breast cancer patients. Breast Cancer Manag. 2016;5(3):119-124.Ortiz M, Lafuente-Sanchis A, Cuevas JM, Zuniga A. Mutational prevalence of BRCA1 and BRCA2 genes in patients with breast and ovarian cancer treated in the health area of La Ribera (Comunidad Valenciana, Spain). Revista Espanola de Patologia. 2016;49(4):214-218.Sun J, Meng H, Yao L, Lv M, Bai J, Zhang J, et al. Germline mutations in cancer susceptibility genes in a large series of unselected breast cancer patients. Clin Cancer Res. 2017;23(20):6113-6119.Appendix 4: Risk of bias within studies reporting data on prevalence (using Joanna Briggs Institute checklist)The Joanna Briggs tool ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><Author>The Joanna Briggs Institute</Author><Year>2017 [accessed 24.11.17]</Year><RecNum>71</RecNum><DisplayText><style face="superscript">71</style></DisplayText><record><rec-number>71</rec-number><foreign-keys><key app="EN" db-id="fe5d02darx2vdyezdr45w2fcx00ad5a5s5rr" timestamp="1549931804">71</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>The Joanna Briggs Institute,</author></authors></contributors><titles><title>The Joanna Briggs Institute critical appraisal tools for use in JBI systematic reviews: checklist for prevalence studies</title></titles><pages>7</pages><dates><year>2017 [accessed 24.11.17]</year></dates><pub-location>Adelaide</pub-location><publisher>The Joanna Briggs Institute</publisher><urls></urls></record></Cite></EndNote> will be used for studies that present prevalence data only.Answers: Yes, No, Unclear or Not/Applicable 1. Was the sample representative of the target population? This question relies upon knowledge of the broader characteristics of the population of interest. If the study is of women or men with breast cancer, knowledge of at least the characteristics, demographics and medical history is needed. The term “target population” should not be taken to infer every individual from everywhere or with similar disease or exposure characteristics. Instead, give consideration to specific population characteristics in the study, including age range, gender, morbidities, medications, and other potentially influential factors. For example, a sample may not be representative of the target population if a certain group has been used (such as those working for one organization, or one profession) and the results then inferred to the target population (ie, working adults). 2. Were study participants recruited in an appropriate way? Recruitment is the calling or advertising strategy for gaining interest in the study and is not the same as sampling. Studies may report random sampling from a population, and the methods section should report how sampling was performed. What sources of data were study participants recruited from? Was the sampling frame appropriate? For example, census data are a good example of appropriate recruitment, as a good census will identify everybody. Was everybody included who should have been included? Were any groups of persons excluded? Was the whole population of interest surveyed? If not, was random sampling from a defined subset of the population employed? Was stratified random sampling with eligibility criteria used to ensure the sample was representative of the population that the researchers were generalizing to? 3. Was the sample size adequate? An adequate sample size is important to ensure good precision of the final estimate. Ideally we are looking for evidence that the authors conducted a sample size calculation to determine an adequate sample size. This will estimate how many subjects are needed to produce a reliable estimate of the measure(s) of interest. For conditions with a low prevalence, a larger sample size is needed. Also consider sample sizes for subgroup (or characteristics) analyses, and whether these are appropriate. Sometimes, the study will be large enough (as in large national surveys) whereby a sample size calculation is not required. In these cases, sample size can be considered adequate. When there is no sample size calculation and it is not a large national survey, the reviewers may consider conducting their own sample size analysis using the following formula: N = Z2P(1-P) d2 Where: ? N = sample size ? Z = Z statistic for a level of confidence ? P = expected prevalence or proportion (in proportion of one; if 20%, P=0.2) ? d = precision (in proportion of one; if 5%, d=0.05) 4. Were the study subjects and setting described in detail? Certain diseases or conditions vary in prevalence across different geographic regions and populations (eg, women vs. men, sociodemographic variables between countries). Has the study sample been described in sufficient detail so that other researchers can determine if it is comparable to the population of interest to them? 5. Is the data analysis conducted with sufficient coverage of the identified sample? A large number of dropouts, refusals or “not founds” among selected subjects may diminish a study’s validity, as can low response rates for survey studies. - Did the authors describe the reasons for nonresponse and compare persons in the study to those not in the study, particularly with regard to their socio-demographic characteristics? - Could the not-responders have led to an underestimate of prevalence of the disease or condition under investigation? - If reasons for nonresponse appear to be unrelated to the outcome measured and the characteristics of nonresponders are comparable to those in the study, the researchers may be able to justify a more modest response rate. - Did the means of assessment or measurement negatively affect the response rate (measurement should be easily accessible, conveniently timed for participants, acceptable in length and suitable in content). 6. Were objective, standard criteria used for measurement of the condition? Here we are looking for measurement or classification bias. Many health problems are not easily diagnosed or defined and some measures may not be capable of including or excluding appropriate levels or stages of the health problem. If the outcomes were assessed based on existing definitions or diagnostic criteria, then the answer to this question is likely to be yes. If the outcomes were assessed using observer-reported or self-reported scales, the risk of over- or under-reporting is increased, and objectivity is compromised. Importantly, determine if the measurement tools used were validated instruments as this has a significant impact on outcome assessment validity. 7. Was the condition measured reliably? Considerable judgment is required to determine the presence of some health outcomes. Having established the objectivity of the outcome measurement instrument (see item 6 of this scale), it is important to establish how the measurement was conducted. Were those involved in collecting data trained or educated in the use of the instrument/s? If there was more than one data collector, were they similar in terms of level of education, clinical or research experience, or level of responsibility in the piece of research being appraised? - Has the researcher justified the methods chosen? - Has the researcher made the methods explicit? (For interview method, how were interviews conducted?) 8. Was there appropriate statistical analysis? As with any consideration of statistical analysis, consideration should be given to whether there was a more appropriate alternate statistical method that could have been used. The methods section should be detailed enough for reviewers to identify the analytical technique used and how specific variables were measured. Additionally, it is also important to assess the appropriateness of the analytical strategy in terms of the assumptions associated with the approach as differing methods of analysis are based on differing assumptions about the data and how they will respond. Prevalence rates found in studies only provide estimates of the true prevalence of a problem in the larger population. Since some subgroups are very small, 95% confidence intervals are usually given. 9. Are all important confounding factors/ subgroups/differences identified and accounted for? Incidence and prevalence studies often draw or report findings regarding the differences between groups. It is important that authors of these studies identify all important confounding factors, subgroups and differences and account for these. 10. Were subpopulations identified using objective criteria? Objective criteria should also be used where possible to identify subgroups (refer to question 6). Note: Copyright ? 2015. 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