Immediate versus delayed reconstruction following surgery
for breast cancer (Review)
DSouza N, Darmanin G, Fedorowicz Z This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2011, Issue 7 http://www.thecochranelibrary.com Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. T A B L E O F C O N T E N T S 1 HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 10 DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . 25 INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . i Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Review] Immediate versus delayed reconstruction following surgery for breast cancer Nigel DSouza 1 , Geraldine Darmanin 2 , Zbys Fedorowicz 3 1 Oxford Deanery, Heatherwood and Wexham Park Hospitals NHS Trust, Slough, UK. 2 London Deanery, Kings College Healthcare Trust, London, UK. 3 UKCC (Bahrain Branch), Ministry of Health, Bahrain, Awali, Bahrain Contact address: Nigel DSouza, Oxford Deanery, Heatherwood and Wexham Park Hospitals NHS Trust, Wexham Park Hospital, Slough, Berkshire, SL2 4HL, UK. n.dsouza15@gmail.com. Editorial group: Cochrane Breast Cancer Group. Publication status and date: Edited (no change to conclusions), published in Issue 9, 2011. Review content assessed as up-to-date: 25 August 2010. Citation: DSouza N, Darmanin G, Fedorowicz Z. Immediate versus delayed reconstruction following surgery for breast cancer. Cochrane Database of Systematic Reviews 2011, Issue 7. Art. No.: CD008674. DOI: 10.1002/14651858.CD008674.pub2. Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. A B S T R A C T Background Breast cancer is the most prevalent cancer in women and has a lifetime incidence of one in nine in the UK. Curative treatment requires surgery, and may involve adjuvant and neo-adjuvant therapy. In many women, post-mastectomy breast reconstruction is essential to restore body image and improve quality of life. Timing of reconstruction may be immediate or delayed following mastectomy. Outcomes such as psychosocial morbidity, aesthetics and complications rates may differ between the two approaches. Objectives To assess the effects of immediate versus delayed reconstruction following surgery for breast cancer. Search methods We searched the Cochrane Breast Cancer Groups Specialised Register on 22 July 2010, MEDLINE fromJuly 2008 to 26 August 2010, EMBASE from 2008 to 26 August 2010 and the WHO International Clinical Trials Registry Platform (ICTRP) on 26 August 2010. Selection criteria Randomised controlled trials (RCTs) comparing immediate breast reconstruction versus delayed or no reconstruction in women of any age and stage of breast cancer. We considered any recognised methods of reconstruction to one or both breasts undertaken at the same time as mastectomy or at any time following mastectomy. Data collection and analysis Two review authors independently screened papers, extracted trial details and assessed the risk of bias in the one eligible study. Main results We included only one RCT that involved 64 women. We judged this study as being at high risk of bias. Post-operative morbidity and mortality were not addressed, and secondary outcomes of patient cosmetic evaluations and psychosocial well-being post-reconstruction were inadequately reported. Based on limited data there was some, albeit unreliable, evidence that immediate reconstruction compared with delayed or no reconstruction, reduced psychiatric morbidity reported three months post-operatively. 1 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Authors conclusions The current level of evidence for the effectiveness of immediate versus delayed reconstruction following surgery for breast cancer was based on a single RCT with methodological aws and a high risk of bias, which does not allow condent decision-making about choice between these surgical options. Until high quality evidence is available, clinicians may wish to consider the recommendations of relevant guidelines and protocols. Although the limitations and ethical constraints of conducting RCTs in this eld are recognised, adequately powered controlled trials with a focus on clinical and psychological outcomes are still required. Given the paucity of RCTs in this subject, in future versions of this review we will look at study designs other than RCTs specically good quality cohort and case- control studies. P L A I N L A N G U A G E S U M M A R Y Immediate versus delayed reconstruction following surgery for breast cancer Curative treatment of breast cancer requires surgery, which can involve a mastectomy to remove the entire breast. Breast reconstruction following mastectomy can be carried out either immediately or as a delayed procedure. Immediate reconstruction is carried out at the same time as surgery while delayed reconstruction may be performed at any time following mastectomy. Several non-randomised studies have reported differences in the psychological benets, aesthetics and complication rates based on the timing of reconstruction. This review sought to compare the effects of the timing of reconstruction on morbidity and mortality, patient satisfaction and psychosocial well-being. Only one eligible randomised controlled trial (RCT) was found, which involved 64 women. However, because a substantial number of participants in the study chose not to undergo delayed reconstruction, it was not possible to make a fair comparison of the mixed group with those participants who underwent immediate reconstruction. Methodological aws and a high risk of bias also diminished the quality of evidence found in the RCT. Since we have only identied one RCT in this area, an updated version of this review will evaluate other study designs specically good quality cohort and case-control studies. Further research should aimto provide reliable evidence for people to make informed decisions as to the best and most appropriate timing of breast reconstruction following surgery for breast cancer. B A C K G R O U N D Description of the condition Breast cancer is a malignant growth of cells originating in breast tissue. It can spread to other parts of the body by growing into adjacent tissues, or by breaking off and spreading via the blood- stream or lymphatic system to seed into a distant organ or tissue, where it may then begin to grow (metastatic spread). Metastatic spread may occur in other organs, such as the liver, lung, brain and bones. Data gathered by the International Agency for Research on Cancer conrm that breast cancer is one of the most common cancers in women, with 1.38 million newcases diagnosed in 2008. Countries in the developed world have the highest age-standard- ised incidence of breast cancer, which in Western Europe is 89.7 per 100,000 women and 76.7 per 100,000 in North America. Al- though the incidence is lower in Eastern Europe, South America, and Western Asia, it is still the most common cancer of women in these geographic regions. In most of Africa, with the possible exception of Southern Africa (41/100,000), the incidence rates are generally lower, ranging from19.3 per 100,000 women in Eastern Africa to 21 per 100,000 in Central Africa (GLOBOCAN 2008). The lifetime risk in the UK for a woman to develop breast cancer is one in nine. Over 81% of breast cancer occurs in women over the age of 50, with the highest risk group category being 50 to 69 years (Ofce for National Statistics 2009). The most common complaint is a breast lump. Other signs or symptoms include skin abnormalities such as tethering (as if the skinis being pulled fromthe inside), ulcerationor local discoloura- tion (peau dorange); nipple changes which may include bleed- ing, inversion or discharge; lumps in the axilla (underarm) or un- commonly, breast pain. Diagnosis is made by triple assessment: clinical examination, radiological assessment which may include mammography or ultrasound, and histopathological assessment of cytology or biopsy. Early breast cancer is often asymptomatic and only detected by screening with mammography. The current ve-year relative survival for localised breast cancer (cancer which has not spread to lymph nodes or sites outside the 2 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. breast) is 98%. If there has been regional spread by direct invasion toadjacent local structures or nearby lymphnodes, survival is 84%. Distant metastatic spread is considered incurable and treatment is directed at improving life expectancy, palliating symptoms and improving quality of life. The most common sites of spread are bone, lung and liver, with an overall ve-year survival rate of 23% for metastatic breast cancer (Jemal 2009). Life expectancy in these cases is related to the extent of metastasis, size of tumour, lymph node involvement and whether major organs are affected. Treatment options for breast cancer are based on tumour type, size, stage, grade, patient genetic predisposition, patient hormone receptor status andpatient preferences, whichmust all be evaluated when choosing the optimum treatment i.e. curative or palliative. Treatment with curative intent requires surgery, with or without radiotherapy and systemic therapy. Surgery and radiotherapy both treat cancer at a specic, local site of disease, with surgery still the primary method for removing cancer. Surgical treatment is directed at the breast and may also include the axilla. Although breast-conserving surgical (BCS) procedures (lumpectomy, quad- rantectomy and segmental mastectomy) tend to be the preferred rst option, mastectomy may be necessary if the cancer is greater than 4 cm, multi-focal, centrally situated or of a particular in- vasive carcinoma subtype. BCS is the surgical removal of the tu- mour and a rim of healthy tissue surrounding the tumour, while mastectomy involves removal of the breast, with or without skin. Both BCS and mastectomy may vary in the extent of surgical resection. Subcutaneous mastectomy removes breast tissue under the skin, while radical mastectomy can remove the entire breast with underlying pectoralis muscle. Radical mastectomy is rarely performed in current practice due to the extensive morbidity it causes. Axillary surgery (removal of associated lymph glands from under the arm) is performed by sentinel lymph node biopsy, axil- lary lymph node biopsy or dissection of many lymph nodes. Sen- tinel lymph node biopsy involves injecting radioisotope dye into the breast tissue around the nipple, and removing the nodes to which the dye spreads. These nodes are taken intra-operatively for microscopic examination by histopathologists. If they are clear, no further lymph nodes need to be removed. If the lymph nodes do show signs of cancer, additional lymph nodes need to be removed. The alternative approach is to proceed with the removal of many lymph nodes based on the stage (spread) and grade of the cancer, alongside imaging results and clinical examination ndings. Treatment with radiotherapy may be given in addition to BCS to decrease the incidence of local cancer recurrence (the cancer returning in the same breast), and may also target the axilla in patients with positive lymph nodes detected by sentinel biopsy or axillary sampling. With certain subtypes of cancer (e.g. ductal carcinoma in situ (DCIS)), radiotherapy may not be indicated. Systemic therapy aims to treat the whole body, not just the lo- cal site of disease, using chemotherapy, hormone treatment or immunotherapy. Hormones such as oestrogen and progesterone can affect the growth of certain types of breast cancer. Selectively blocking oestrogen action or production can shrink large cancers, decreasing the chances of local recurrence and the likelihood of metastatic spread. There are three types of hormone therapy; ta- moxifen,aromatase inhibitors and pituitary suppressors. Tamox- ifen directly blocks the effect of oestrogen on tissue. Aromatase inhibitors e.g. anastrozole, block oestrogen production from the adrenal glands in post-menopausal women. Pituitary suppressants e.g. goserelin, block the hormone pathways that lead to oestrogen production. An immunotherapeutic agent, herceptin, can reduce the chance of recurrence and disease progression in women who carry the HER2-positive receptor. In some countries, prophylactic bilateral mastectomies are offered to women who have inherited BRCA gene mutations that predispose them to breast cancer. Neoadjuvant therapy may be given before surgery in an attempt to shrink tumours pre-operatively, and adjuvant therapy is often givenafter surgery to reduce the chance of recurrence, and this may include chemotherapy, hormone therapy or targeted biological therapy. Description of the intervention Breast reconstruction is essential for many women to restore body image and improve quality of life post-mastectomy. Treatment aims to manage the psychological impact of breast cancer and in- cludes breast reconstruction and psychological support. Recon- structionconsists of the rebuilding of a womans breast using either tissue from other parts of the body or implantable devices such as silicone or saline implants. This often includes the reformation of a natural looking areola and nipple. A range of surgical options for reconstruction are available. Autologous tissue procedures Autologous reconstruction uses a patients own tissue to replace lost breast tissue. This may be carried out as an immediate recon- struction, in the same operation as mastectomy once it is com- pleted. It may also be carried out as a delayed reconstructionproce- dure, which occurs any time after the initial operation but usually after two months to allow skin to heal. Autologous reconstruction may be contraindicated in cases such as previous major surgery in the required tissue, systemic medical conditions such as hyper- tension, chronic obstructive pulmonary disease, diabetes, patients who smoke or who have too high or too low a body mass index (BMI). 1. Latissimus dorsi myocutaneous ap: skin and muscle aps can be used to cover areas of excised tissue. This is achieved by cutting a skin island and pivoting it under the axilla whilst retaining the same blood supply. The ap can be used to cover an implant, or on its own in small-breasted women. 2. Transverse rectus abdominus myocutaneous (TRAM) aps: these are harvested and transferred from the abdomen to the chest wall by joining the blood vessels of the ap (the pedicle) to 3 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. the internal mammary vessels in the chest. Blood supply to TRAM aps is variable. Pedicled TRAM aps require the entire rectus abdominus while microvascular TRAM aps require a (much) smaller proportion of muscle. 3. Deep inferior epigastric perforator (DIEP) aps: these are created from the lower abdomen without removal of muscle. Their use is limited by anatomical constraints that cannot be predicted pre-operatively. 4. Gluteal artery perforator (GAP) aps: these aps include the skin and subcutaneous tissue based on the inferior and superior gluteal vessels where the gluteal muscle is not removed. This procedure is generally considered a second-line option. Tissue expanders and implantable devices Implantable devices such as silicone or saline implants can be used immediately if there is sufcient skin or soft tissue coverage pro- vided by a skin ap. However, if there is insufcient tissue to cover the implant, reconstruction can be delayed while a tissue expander is used. Tissue expanders are placed under the pectoralis muscle and can be inated and later replaced with a denitive implant. Ports located in the expanders allow them to be lled with saline in the post-operative period. Expansion causes gradual stretching and growth of the soft tissue such that the excess skin can then be used at that site to cover an implant. How the intervention might work The timing and decision of when to carry out breast reconstruc- tion remains controversial and will often depend on individual circumstances, in addition to whether adjunctive radiotherapy is required. In planning reconstruction it is important that the pri- mary focus should be effective cancer treatment, around which the aesthetic goals of reconstruction must be tailored. Immediate reconstruction This is performed at the time of the mastectomy and is indicated primarily for patients who are unlikely to require additional ra- diotherapy. Predicting whether radiotherapy will be required after surgery is not always feasible and in borderline cases may result in a surgeon advocating delayed reconstruction. A number of studies have shown that reconstruction is onco- logically safe directly after mastectomy even in advanced disease, thereby making this procedure even more acceptable for patients (Giacalone 2010; Langstein 2003; Newman 1999). It is claimed that early reconstruction tends to lead to better aesthetic outcomes (McCarthy 2005) since the breast envelope is preserved together with the inframammary fold and offers a better prospect of recre- ating a natural shape, with more symmetry to the breast. Adding a myocutaneous ap (well-vascularised and non-radiated) at the time of mastectomy can also be advantageous as it can promote tissue healing (Bostwick 1990). Immediate reconstructionfollowing breast cancer surgery is recog- nised to be an important consideration in the reduction of anx- iety levels as well as in improving self-esteem and quality of life (Drucker-Zertuche 2007). One study reported that 95% of the patients who had received immediate reconstruction were content with the outcome as compared with 76%of those who underwent delayed reconstruction and who also indicated that they would have preferred immediate reconstruction (Al-Ghazal 2000). Controversy remains over the possible detrimental effects of adju- vant radiotherapy on immediate breast reconstruction. A number of studies have shown that radiation after immediate reconstruc- tion gives poor results and compromises aesthetic results. When breasts that have been reconstructed with implants are subjected to radiotherapy, complications may arise and these can include impaired skin healing, brosis, implant extrusion and capsular contractures (Behranwala 2006, Forman 1998; Kronowitz 2009; Tallet 2003; Whiteld 2009). Complications can also occur when autologous aps undergo radiotherapy. Early complications in- clude thrombosis, ap necrosis or loss, and local wound-healing problems, while late complications included hyperpigmentation, fat necrosis, volume loss, and ap contracture (Kronowitz 2009; Kronowitz 2004; Rogers 2002; Spear 2005; Thomson 2008; Tran 2001). Tissue expansion is often poorly tolerated by many pa- tients (Tallet 2003) and can lead to complications such as a con- cave deformity of the chest wall (Fodor 1989). Several studies have reported contradictory results which suggest that careful choice of immediate reconstruction technique or adjuvant therapy can minimise some of the adverse events that can occur after adjuvant therapy (Hussien 2004; von Smitten 1992; Williams 1995). Delayed reconstruction Delayed reconstruction is indicated when post-mastectomy radio- therapy is required, or likely to be required. A further indication would be when patients are not ready or willing to engage in plan- ning a reconstructive procedure until more time has passed since their diagnosis. The delayed approach is also used in partial breast mastectomy, when the margins of resection are not known at the time of the operation and further excision may be required. De- layed reconstruction can be technically challenging because radi- ation can lead to tissue brosis in the chest wall tissue. Implants may be placed at the time of mastectomy, as part of a delayed procedure, before irradiation, after which autologous aps are created. However, this may also result in sub-optimal outcomes with worse cosmetic results, more painful expansion and greater risk of revision surgery (Cordeiro 2004; Krueger 2001). Patients who select the delayed approach have more time to con- sider the various surgical options. A patient has to cope with the burden of the diagnosis and the ongoing psychological pressures 4 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. of dealing with the physical and social consequences of the disease. Delayed reconstruction gives her the time to seek advice fromplas- tic and breast surgeons, thereby allowing more time for evaluation of the various reconstructive techniques available once denitive cancer treatment has been completed. In patients who have un- dergone radiation therapy, it also permits clinical assessment of the irradiated tissue and complications of radiotherapy such as non- viable tissues which can be removed during reconstruction. The disadvantages of a delayed approach are largely psychological, due to the burden of patients living with breast deformity until reconstruction is completed. Some studies have reported this as leading to lower self-esteem and body image, causing depression and anxiety (Fernandez-Delgado 2008). There are also technical difculties with a delayed approach, beyond the difculties of deal- ing with irradiated tissue. Larger aps are required because of the need for skin replacement, symmetry is difcult to achieve, and contralateral mastopexy (lifting breast tissue and removing skin) may be required in many cases. However, some studies have shown that delayed procedures have had excellent long-term aesthetic re- sults (Schuster 1992). Patients are oftencounselled to have realistic expectations for the aesthetic outcome of delayed reconstruction, especially if the eld was previously irradiated. Patient evaluation of aesthetic outcomes can vary depending on the time reconstruc- tion takes place. Why it is important to do this review Outcomes such as morbidity, cosmetic outcomes and psycholog- ical benets may differ between immediate or delayed breast re- construction post-mastectomy. A summary of the evidence for the benets, both clinical and psychological, could help facilitate bet- ter shared decision-making between clinicians and patients on the best treatment. O B J E C T I V E S To assess the effects of immediate versus delayed reconstruction following surgery for breast cancer. M E T H O D S Criteria for considering studies for this review Types of studies Randomised controlled clinical trials (RCTs). Types of participants Women in any age group with any stage of breast cancer in either of the following two treatment groups. 1. Delayed breast reconstruction to one or both breasts post- mastectomy. 2. Immediate reconstruction to one or both breasts concurrent with mastectomy. The only included trial evaluated both treatments. Types of interventions We compared immediate reconstruction versus delayed recon- struction. We considered any appropriate and recognised meth- ods of reconstruction. We included studies in which immediate reconstruction was compared with the option of delayed or no treatment. See Differences between protocol and review Types of outcome measures Primary outcomes 1. Post-operative morbidity (number of surgical complications) and mortality. Secondary outcomes 1. Patient cosmetic or functional satisfaction with reconstruction, assessed using any validated generic or disease- specic questionnaire. 2. Psychosocial well-being post-reconstruction, assessed using any validated generic or disease-specic scale. Search methods for identication of studies See: Breast Cancer Group methods used in reviews. Electronic searches For the identication of studies we searched the following databases. (1) Cochrane Breast Cancer Group Specialised Register Details of search strategies used by the Group for the identication of studies and the procedure used to code references are outlined in the groups module (Cochrane Breast Cancer Group 2009). We extracted trials coded with the key words surgery, carcinoma in situ, early breast cancer, locally advanced breast cancer and ad- vanced breast cancer for consideration. We conducted the search on 22 July 2010. 5 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. (2) MEDLINE (via OVID) from July 2008 onwards We ran the subject search with the Cochrane Highly Sensitive SearchStrategy (CHSS) for identifying randomisedtrials inMED- LINE: sensitivity-maximising version (2008 revision) as refer- encedinChapter 6.4.11.1anddetailedinbox 6.4.c of the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 (up- dated February 2008) (Higgins 2008). See Appendix 1 for the full search strategy conducted on 26 August 2010. (3) EMBASE (via OVID) from 2008 onwards We conducted the search on the EMBASE database (i.e. from 2008) on 26 August 2010. See Appendix 2 for the full search strategy. Searching other resources 1. We searched bibliographical references of identied studies for references to additional studies. 2. We searched clinical trials registries: the WHO International Clinical Trials Registry Platform (ICTRP) search portal http://apps.who.int/trialsearch/ on 26 August 2010. See Appendix 3. Although we did not impose language restrictions on included studies, we did not identify any relevant reports in languages other than English. We contacted the publisher of an earlier review ( Anthony 1995), that evaluated the effects of immediate versus delayed reconstruction but we were unsuccessful in obtaining a copy of the report. Data collection and analysis Selection of studies Two review authors (Nigel DSouza (ND) and Zbys Fedorowicz (ZF)) independently assessedthe abstracts of studies resulting from the searches. We obtained full copies of all relevant and potentially relevant studies, those appearing to meet the inclusion criteria, and those for which there were insufcient data in the title and abstract to make a clear decision. The two review authors independently assessed the full-text papers and resolved any disagreement on the eligibility of included studies through discussion and consensus with the third author (Geraldine Darmanin (GD)). We excluded all irrelevant records andnoteddetails of the studies andthe reasons for their exclusion in the Characteristics of excluded studies table in RevMan 5 (RevMan 2008). Data extraction and management We entered study details into the Characteristics of included studies table in RevMan 5. We collected outcomes data using a pre-determined formdesigned for this purpose and we entered the data into Table 1. We only included data if we reached consensus or resolved any disagreements by consulting with a third review author (GD). We extracted the following details. 1. Trial methods: (a) method of allocation; (b) masking of participants, trialists and outcomes assessors; (c) exclusion of participants after randomisation and proportion and reasons for losses at follow-up. 2. Participants: (a) country of origin and location: private clinic or academic institute; (b) sample size; (c) age; (d) sex; (e) inclusion and exclusion criteria. 3. Intervention: (a) type; (b) length of time in follow-up. 4. Control: (a) type; (b) length of time in follow-up. 5. Outcomes: (a) primary and secondary outcomes mentioned in the Types of outcome measures section of this review. If stated, we planned to record the sources of funding. The review authors intended to use this information to help them assess heterogeneity and the external validity of the trials. Assessment of risk of bias in included studies Each reviewauthor assessed and graded the selected trial following the domain-based evaluation described in the Cochrane Handbook for Systematic Reviews of Interventions 5.0.0 (Higgins 2008). We compared these evaluations and we resolved any inconsistencies and disagreements by discussion. We assessed the following domains as Yes (i.e. low risk of bias), Unclear (i.e. uncertain risk of bias) or No (i.e. high risk of bias): sequence generation; allocation concealment; blinding (of participants, personnel and outcome assessors); incomplete outcome data; and selective outcome reporting. We reported these assessments in the Risk of bias table in the Characteristics of included studies section of the review. Measures of treatment effect The outcomes we specied for this reviewwere mortality, morbid- ity, quality of life and included measures of self-esteemand patient satisfaction with the procedures. We intended to assess continu- ous data using standardised mean differences (SMD), and binary outcomes using odds ratios (OR). We planned to divide outcome variables reported at different time points into immediate, short and long term follow-up. 6 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Unit of analysis issues We expectedthat eligible trials may have involvedparticipants with bilateral breast reconstruction and therefore the unit of analysis would have been at the level of randomisation of either the breast or the individual, whichever was appropriate. Dealing with missing data In view of the age of the included study, we did not attempt to retrieve missing data from the investigators. Missing data were largely attributable to withdrawals/protocol deviations and thus we have only provided a descriptive summary of the results as reported. Assessment of heterogeneity We only included one trial in this review, therefore, it was not feasible to assess heterogeneity but in future updates and if further trials are identied we will apply the following methods. We will assess clinical heterogeneity by examining the characteris- tics of the studies, the similarity between the types of participants, the interventions and the outcomes, as specied in the criteria for included studies. In view of the expectation of a degree of clinical heterogeneity between the studies we intend to use the random- effects model with studies grouped by action. We will assess statistical heterogeneity using the I 2 statistic (Higgins 2003). We will evaluate the I 2 statistic as follows: 0% to 40%: might not be important; 30% to 60%: may represent moderate heterogeneity; 50% to 90%: may represent substantial heterogeneity; 75% to 100%: considerable heterogeneity. Assessment of reporting biases If further eligible studies are identied, we will follow the recom- mendations on testing for funnel plot asymmetry as described in section 10.4.3.1 of the Cochrane Handbook for Systematic Reviews of Interventions 5.0.0 (Higgins 2008). Funnel plot asymmetry may be due to reporting bias, and we will address this possibility in the Discussion if appropriate. We recognise that these results need to be interpreted cautiously if analysing small study effects with dichotomous outcomes. Data synthesis If adequate data are available in future updates, we will use the following methods of data synthesis. Two review authors (ZF and ND) will analyse the extracted data and report them as specied in Chapter 9 of the Cochrane Hand- book for Systematic Reviews of Interventions Version 5.0.0 (Higgins 2008). Please see Unit of analysis issues. The outcomes speciedfor this reviewinclude morbidity andqual- ity of life, therefore, we will make decisions regarding if and how to combine separate outcomes data depending on if and how this information is collected in each trial. The data are most likely to be assessed as ordinal outcome data. However, our decisions for analysis will be guided explicitly by, and based on,the recommen- dations for dealing with effect measures for ordinal outcomes and measurement scales in section 9.2.4 of the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 (Higgins 2008). We will report data and if feasible, we will synthesise the data ac- cording to this guidance. We will use the random-effects model for the synthesis and meta- analysis of any quantitative data. Inthe event that there are insufcient clinically homogeneous trials for any specic intervention or insufcient study data that can be pooled, we will present a narrative synthesis. Subgroup analysis and investigation of heterogeneity Lack of included studies did not permit a subgroup analysis, but if data are subsequently available for a sufciently large number of participants, we will undertake subgroup analyses in which par- ticipants are categorised by age, staging of breast cancer at time of diagnosis, and the type of reconstruction performed. Sensitivity analysis We did not carry out a sensitivity analysis but if future updates in- clude a sufcient number of studies, we plan to conduct sensitivity analyses to assess the robustness of our review results by repeating the analysis with the following adjustments: exclusion of studies with unclear or inadequate allocation concealment, blinding of outcomes assessment and completeness of follow-up. R E S U L T S Description of studies See: Characteristics of includedstudies; Characteristics of excluded studies. See: Characteristics of included studies and Characteristics of excluded studies. Results of the search Fromthe electronic searches, including the recent updates (August 2010), we retrieved 411 references to studies. After examination of the titles andabstracts of these references, we eliminatedall of those which did not match our inclusion criteria and those which were clearly ineligible from the review. We obtained full text copies of 7 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. the remaining nine potentially eligible trials for further evaluation. The review authors discussed the eligibility of these trials and resolved any remaining uncertainties by consensus. Subsequently only one study proved to be eligible for inclusion in this review and therefore, we excluded the remaining eight studies. Included studies We included only one study in this review (Dean 1983). Characteristics of the trial setting and investigators This RCT was conducted at the Longmore Hospital, Edinburgh between October 1978 and July 1980. The providers of care were hospital staff in the breast surgery unit and the outcomes assessors were the surgeons, psychiatrists, psychologists and nurse counsel- lors. Characteristics of the participants The participants were 64womenbelowthe age of 60, and although the report indicated that there was no signicant difference in age, marital status, TNM (tumour, node, metastasis) staging or treat- ment options (radiotherapy, chemotherapy and oophorectomy), the investigators provided very limited demographic information. Characteristics of the interventions All of the participants underwent total mastectomy which in- cluded axillary node clearance for some participants. This was fol- lowed by immediate reconstruction for 33 participants or the op- tion of delayed reconstruction at 12 months post-mastectomy for 31 participants. A sialastic subpectoral prosthesis (Heyer-Schultz) was provided for 33 participants at the time of mastectomy. The 31 participants in the delayed reconstruction group were advised about an external prosthesis and although all patients were offered delayed reconstruction, only six took up the option 12 months after mastectomy. Post-operative care consisted of penicillin V (1 gm/day) and u- cloxacillin (1 gm/day) orally for ve days. Patients with positive nodes received either radiotherapy, or chemotherapy/oophorec- tomy. Characteristics of the outcome measures Assessments were made at three and 12 months post-operatively, which included morbidity across different domains (psychiatric, sexual, social, marital and work) using Spitzers Research Diagnos- tic Criteria for major depression or Feighner Criteria for depres- sion or anxiety. A self-rated general health questionnaire was used as a screening instrument for psychiatric morbidity. Cosmetic assessment of the implant group was carried out at nought to 17 months post-operatively by a panel of two surgeons, a psychiatrist, a psychologist and a nurse counsellor. A non val- idated tool was used to evaluate cosmetic outcomes, which in- cluded assessments of the symmetry of the breast both with and without a bra, rated on a three-point scale of 5 = good, 3 = average, 1 = poor. Patient assessment of cosmetic results using a scale rated as ugly/not ugly/almost normal were also undertaken 3 and 12 months post-operatively (Table 1). Excluded studies All of the studies which were excluded from this review and the reasons for their exclusion are reported in the Characteristics of excluded studies table. Risk of bias in included studies We assessed the single included study as having a high risk of bias (plausible bias that seriously weakens condence in the results) because one or more of the criteria were not met. Further details of the assessments of these criteria are available in the Risk of bias table in the Characteristics of included studies and are also presented in the Risk of bias graph in Figure 1 and the Risk of bias summary in Figure 2. 8 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Figure 1. Risk of bias graph: review authors judgements about each risk of bias item presented as percentages across all included studies. Figure 2. Risk of bias summary: review authors judgements about each risk of bias item for each included study. 9 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. We based these assessments on the inadequate reporting of the criteria that are a prerequisite in the evaluation of methodological rigour in terms of trial design and conduct. Although conceal- ment of the allocation sequence and blinding are considered to be key domains in the assessment of risk of bias, the investigators provided insufcient detail to enable accurate judgements to be made. Protocol deviation and losses to follow-up with incomplete outcome data were other important sources of potential bias in the included study (see Risk of bias table in Characteristics of included studies). Allocation The methods used to generate the allocationsequence and howthe sequence was concealed, such that participants and investigators enrolling participants could not foresee the upcoming assignment, are the most important and sensitive indicators that bias has been minimised in a clinical trial. Randomisation and allocation was reported to have been carried out in the operating room post- mastectomy but no further details were provided and therefore we considered the judgement for this domain to be unclear. Blinding Blinding of the participants and caregivers was not feasible in this study because of the nature of the actual interventions offered and received. However, it should have been possible to at least ensure blinding of outcomes assessments by excluding the care givers and anyone directly involved with the conduct of the trial from evaluating the outcomes. Incomplete outcome data Incomplete outcome data presented the highest risk of bias in this study. Although the trial compared immediate with delayed breast reconstruction, only six out of 31 women took up the option of delayed reconstruction and no follow-up data were reported for these participants or those who chose not to have the reconstruc- tion. Two participants in the implant group were not seen for pre- operative psychiatric assessments, a further four participants either refused to return or could not be traced and 14 out of 64 of the health questionnaires were not returned. The report did not clearly and comprehensively report the number of losses pertaining to each of the intervention groups or the reasons for these losses of outcome data. The reporting of outcome data was not clear and in most instances it was not possible to disentangle the outcome data separately for each of the intervention groups. Selective reporting The reporting of outcomes in this older study although not ideal was somewhat consistent with the editorial style and standards existing at the time of its publication. Although the protocol was not available for the included study, based on the information in the methods section of the report, the investigators appear to have reported some data on most of their prespecied outcomes and therefore, we judged the study to be relatively free of selective reporting. Other potential sources of bias A total of 125 women were invited to enter the study out of which only 64 were enrolled and its possible that this may have introduced an element of sampling bias into the study. Effects of interventions We could not present data on the effects of these interventions graphically in RevMan, and therefore some of these have been reported together with relevant comments inthe Data and analyses section of the review and in Table 2. We categorised the one RCT included in this review as high risk of bias and therefore caution is advised in interpreting the results and extrapolating the effects of interventions. D I S C U S S I O N Summary of main results We only included one RCT in this review. It was disappointing to see the paucity of prospective RCTs comparing these interven- tions and that our primary outcome of post-operative morbidity (number of surgical complications) and mortality had not been as- sessed in the single included study. Only our secondary outcomes of cosmetic satisfaction and psychosocial well-being had been ad- dressed but these data were incomplete due to protocol deviation by a substantial number of participants in the delayed treatment arm. Based on data collected from psychiatric interviews of the participants and self-rated health questionnaires there was some, albeit limited and unreliable, evidence that immediate reconstruc- tion compared with delayed or no reconstruction reduced psychi- atric morbidity expressed as the case rate at three months post- operatively. 10 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Overall completeness and applicability of evidence The included RCT was conducted over 25 years ago, limiting its applicability to current surgical practice. Although sialastic im- plants are still used in reconstruction, autologous aps tend to pro- vide improved cosmetic outcomes and are more commonly used in most specialist centres. The review also failed to identify any RCTs evaluating the evidence for the effectiveness of other types of implants and some of the other surgical procedures. Quality of the evidence Although we considered the included RCT to be of sub-optimal quality and assessed it as being at high risk of bias, we have reported its results as it was the only prospective RCT that matched our inclusion criteria. We are unaware of any unpublished studies, and currently there are no ongoing RCTs listed on the WHO ICTRP search portal. Limitations in study design The overall clinical design of the included study was inadequate and we have reported the limitations of its methodological quality in our assessment of the risk of bias and include the following. 1. Inadequate reporting of the methods used to generate the sequence, to conceal the allocation in addition to a lack of adequate measures to blind outcomes assessors. The lack of available additional or incomplete trial information and data prevented an accurate assessment of the risk of bias. 2. Outcome data were either incomplete or not clearly reported which meant that we could not enter data into a RevMan analysis. Directness of evidence Participants in the control group in the included study were given the option to forego reconstruction at a later date. Twenty-ve of the 31 participants did not proceed to reconstruction, resulting in the trial failing to provide a reliable direct comparison of the benets of immediate versus delayed reconstruction. Moreover, in view of the low take-up of delayed reconstruction any direct comparisons of, for example, the cosmetic effects of immediate versus no reconstruction, cannot be considered a fair comparison and would thus limit the generalisability of any evi- dence. This holds equally true for the comparisons of complica- tions of surgery with immediate versus no reconstruction, because it would not be possible to include assessments of complications after delayed reconstructive surgery. Patient-preferred primary outcomes are a pre-requisite for inform- ing evidence-based clinical decision-making and thus the absence of data from RCTs on certain patient-important outcomes i.e. as- sessments of post-operative morbidity (number of surgical com- plications) and mortality justies further downgrading of the level of evidence. Inconsistency of results As only one RCT was included in this review, this assessment was not applicable. Imprecision of results The limited amount of outcome data available from this single trial did not permit any assessment of the precision of the results. Probability of publication bias We could not estimate publication bias as only one trial was in- cluded in this review. Potential biases in the review process We did not identify any sources of potential bias in the review process. Agreements and disagreements with other studies or reviews This reviewshares some of the conclusions reached by other cohort studies and reviews (Atisha 2009; Fischbacher 2002; Harcourt 2001) which have focused on this research question. All of these have emphasised the considerable heterogeneity in participants in individual studies and between studies. They also found a paucity of methodologically rigorous research exploring clinical and psy- chosocial outcomes following immediate or delayed breast recon- struction. The majority of studies conducted have been retrospec- tive analyses. Prospective studies that have been conducted lack comparison or control groups, and have reported outcomes that have been evaluated using different questionnaires or assessment tools, and therefore do not permit fair comparisons or synthesis of data. Much of this evidence from prospective trials is based on cohort studies (Al-Ghazal 2000; Alderman 2002; DeBono 2002; Francel 1993; Mandrekas 1995). One systematic review (Fischbacher 2002) included a series of co- hort studies in addition to a single RCT (Dean 1983) which, in contrast to our assessment, the authors considered to be of mod- erate quality. The conclusions reached in a more recent system- atic review (Guyomard 2007) pointed to the very limited number of studies evaluating important patient reported outcomes (PRO) of patient satisfaction. The review authors also reported multiple aws in methodology of the few included trials which made their 11 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. analysis difcult and limited the validity and subsequent general- isability of any of their results. However, in agreement with our review, the authors stated that further research is required and that future trials should be robust in quality to ensure reliable assess- ment of relevant patient-preferred outcomes. The summary in a literature review (Harcourt 2001) indicated that there was still uncertainty about which treatment confers the greatest psychological benet and that further research needs to consist of studies with a multi-centred prospective design com- bining both qualitative and quantitative components. In contrast with most of these reviews the investigators in a prospective cohort study reported psychosocial benets and body image gains which persisted at two years following immediate reconstruction (Atisha 2009). Although we were unable to obtain copies of an earlier review (Anthony 1995) which evaluated the effects of immediate versus delayed reconstruction, this review had been assessed by Fischbacher 2002 who reported a number of methodological lim- itations including the lack of a systematic assessment of the quality and relevance of studies. A U T H O R S C O N C L U S I O N S Implications for practice We included only one RCT that, which did not consider our pri- mary outcome of post-operative surgical complications and only partially addressed our pre-specied secondary outcomes of psy- chosocial well-being post-reconstruction in this review. The nd- ing that immediate reconstruction reduced psychiatric morbidity at three months should only be accepted while acknowledging the methodological shortcomings and high risk of bias inherent in the trial. The application of these ndings is further limited given that the surgical technique for immediate reconstruction in this 27-year old trial is not current recommended practice. Un- fortunately, the very limited number of study participants in the control (delayed intervention) group in the included study who later decided to undergo reconstruction were not analysed and the results of this subgroup might have shed light on important psychological or cosmetic outcomes. The included trial provides very limited evidence which is likely to inform decision-making in clinical practice. Implications for research The paucity of relevant trials, illustrated by a single study carried out over 25 years ago, points to the need for further research in this eld. One of the main barriers to further research would appear to be that the benets of post-operative radiotherapy to the breast are well known with regards to recurrence (Whelan 2000), if not on overall mortality (Early Breast Cancer Trialists Collaborative Group). Immediate reconstruction may not be carried out if ra- diotherapy is planned, with its recognised and potentially adverse aesthetic outcomes. Constraints in terms of study design, and in particular RCTs, has meant that much of the previous research consists of cohort stud- ies, audits and surveys rather than large-scale trials. The inade- quate methodological quality of many of these was highlighted in Guyomard 2007, and in spite of this, there is well-documented resistance to RCTs in the evaluation of psychological outcomes for these interventions (Atisha 2009; Harcourt 2001). The ethical obstacles to randomised trials have been attributed to the removal of womens input into decision-making (Harcourt 2001). This re- port found that in Dean 1983, a lack of participant control over the timing or type of reconstruction raises serious ethical concerns, since involvement in decision-making may be a crucial factor in improving psychological outcomes. However, given that RCTs have been and are still being conducted in surgical domains where shared clinical decision-making is still the norm, and have yielded valuable information, the question is why this should not be possible in breast reconstruction. Since RCTs remain the most reliable study design to remove confound- ing and sources of bias, modications such as the Zelens design with double randomised consent may have implications for future research. Future randomised controlled trials must be well designed, con- ducted and adequately delivered with subsequent reporting, in- cluding high quality descriptions of all aspects of methodology. Rigorous reporting needs to conform to the Consolidated Stan- dards of Reporting Trials (CONSORT) statement (www.consort- statement.org/) and this will enable appraisal and interpretation of results, and accurate judgements to be made about the risk of bias and the overall quality of the evidence. Although it is uncertain whether reported quality mirrors actual study conduct, it is note- worthy that studies with unclear methodology have been shown to produce biased estimates of treatment effects (Schulz 1995). Ad- herence to guidelines, such as the CONSORT statement, would help ensure complete reporting. For further research recommendations based on the EPICOT for- mat (Brown 2006) please see (Table 2). A C K N O W L E D G E M E N T S The authors would like to acknowledge the support they have received from the Cochrane Breast Cancer Group in conducting this review. 12 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. R E F E R E N C E S References to studies included in this review Dean 1983 {published data only} Dean C, Chetty U, Forrest APM. Effects of immediate breast reconstruction on psychosocial morbidity after mastectomy. Lancet 1983;1(8322):45962. References to studies excluded from this review Alderman 2002 {published data only} Alderman AK, Wilkins EG, Kim HM, Lowery JC. Complications in postmastectomy breast reconstruction: two-year results of the Michigan Breast Reconstruction Outcome Study. Plastic and Reconstructive Surgery 2002; 109(7):226574. [PUBMED: 12045548] Atisha 2009 {published data only} Atisha D, Alderman AK, Janiga T, Singal B, Wilkins EG. The efcacy of the surgical delay procedure in pedicle TRAM breast reconstruction. Annals of Plastic Surgery 2009;63(4):3838. [PUBMED: 19770703] Cheng 2006 {published data only} Cheng MH, Lin JY, Ulusal BG, Wei FC. Comparisons of resource costs and success rates between immediate and delayed breast reconstruction using DIEP or SIEA aps under a well-controlled clinical trial. Plastic and Reconstructive Surgery 2006;117(7):213942. Fernandez-Delgado 2008 {published data only} Fernandez-Delgado J, Lopez-Pedraza MJ, Blasco JA, Andradas-Aragones E, Sanchez-Mendez JI, Sordo-Miralles G, et al.Satisfaction with and psychological impact of immediate and deferred breast reconstruction. Annals of Oncology 2008;19(8):14304. [PUBMED: 18390839] Harcourt 2003 {published data only} Harcourt DM, Rumsey NJ, Ambler NR, Cawthorn SJ, Reid CD, Maddox PR, et al.The psychological effect of mastectomy with or without breast reconstruction: a prospective, multicenter study. Plastic and Reconstructive Surgery 2003;111(3):10608. [PUBMED: 12621175] Neyt 2005 {published data only} Neyt MJ, Blondeel PN, Morrison CM, Albrecht JA. Comparing the cost of delayed and immediate autologous breast reconstruction in Belgium. British Journal of Plastic Surgery 2005;58(4):4937. [PUBMED: 15897033] Roth 2007 {published data only} Roth RS, Lowery JC, Davis J, Wilkins EG. Persistent pain following postmastectomy breast reconstruction: long- term effects of type and timing of surgery. Annals of Plastic Surgery 2007;58(4):3716. [PUBMED: 17413877] Wilkins 2000 {published data only} Wilkins EG, Cederna PS, Lowery JC, Davis JA, Kim HM, Roth RS, et al.Prospective analysis of psychosocial outcomes in breast reconstruction: one-year postoperative results from the Michigan Breast Reconstruction Outcome Study. Plastic and Reconstructive Surgery 2000;106(5):1014-25; discussion 1026-7. [PUBMED: 11039373] Additional references Al-Ghazal 2000 Al-Ghazal SK, Sully L, Falloweld L, Blamey RW. The psychological impact of immediate rather than delayed breast reconstruction. European Journal of Surgical Oncology 2000; Vol. 26, issue 1:17-9. Anthony 1995 Anthony D. Immediate breast reconstruction following mastectomy for cancer of the breast. Bristol, South and West Regional Health Authority. Development and Evaluation Committee Reports 1995;41:unavailable. Behranwala 2006 Behranwala KA, Dua RS, Ross GM, Ward A, Ahern R, Gui GP. The inuence of radiotherapy on capsule formation and aesthetic outcome after immediate breast reconstruction using biodimensional anatomical expander implants. Journal of Plastic Reconstructive and Aesthetic Surgery 2006; 59(10):104351. [PUBMED: 16996426] Bostwick 1990 Bostwick J. Reconstruction after mastectomy. Surgical Clinics of North America 1990;70(5):1125-40. Brown 2006 Brown P, Brunnhuber K, Chalkidou K, Chalmers I, Clarke M, Fenton M, et al.How to formulate research questions. BMJ 2006;333(7572):8046. Cochrane Breast Cancer Group 2009 Wilcken N, Ghersi D, Brunswick C, Clarke M, Dinh P, Ganz P, et al. Cochrane Breast Cancer Group. In: The Cochrane Library, 2009, Issue 3. Chichester: Wiley-Blackwell. Updated quarterly. http:// www.mrw.interscience.wiley.com/cochrane/clabout/articles/ BREASTCA/frame.html. Cordeiro 2004 Cordeiro PG, Pusic AL, Disa JJ, McCormick B, VanZee K. Irradiation after immediate tissue expander/implant breast reconstruction: outcomes, complications, aesthetic results, and satisfaction among 156 patients. Plastic and reconstructive surgery 2004;113(3):87781. DeBono 2002 DeBono R, Thompson A, Stevenson JH. Immediate versus delayed free TRAM breast reconstruction: an analysis of perioperative factors and complications. British Journal of Plastic Surgery 2002;55(2):1116. [PUBMED: 11987942] Drucker-Zertuche 2007 Drucker-Zertuche M, Robles-Vidal C. A 7 year experience with immediate breast reconstruction after skin sparing mastectomy for cancer. European Journal of Surgical Oncology 2007;33(2):140-6. Early Breast Cancer Trialists Collaborative Group Early Breast Cancer Trialists Collaborative Group 2000. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of 13 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. the randomised trials. Lancet 2000;355(9217):175770. [PUBMED: 10832826] Fischbacher 2002 Fischbacher, C. Bazian Ltd (Editors). Immediate versus delayed breast reconstruction. STEER: Succinct and Timely Evaluated Evidence Reviews. Wessex Institute for Health Research & Development, University of Southampton. Available from www.signpoststeer.org 2002; Vol. 2, issue 17. Fodor 1989 Fodor PB, Swistel AJ. Chest wall deformity following expansion of irradiated soft tissue for breast reconstruction. New York State Journal of Medicine 1989;89(7):419-20. Forman 1998 Forman DL, Chiu J, Restifo RJ, Ward BA, Haffty B, Ariyan S. Breast reconstruction in previously irradiated patients using tissue expanders and implants: a potentially unfavorable result. Annals of Plastic Surgery 1998;40(4): 3634. Francel 1993 Francel TJ, Ryan JJ, Manson PN. Breast reconstruction utilizing implants: a local experience and comparison of three techniques. Plastic and Reconstructive Surgery 1993;92 (5):78694. [PUBMED: 8415959] Giacalone 2010 Giacalone PL, Rathat G, Daures JP, Benos P, Azria D, Rouleau C. New concept for immediate breast reconstruction for invasive cancers: feasibility, oncological safety and esthetic outcome of post-neoadjuvant therapy immediate breast reconstruction versus delayed breast reconstruction: a prospective pilot study. Breast Cancer Research and Treatment 2010;122(2):43951. [PUBMED: 20502959] GLOBOCAN 2008 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10. International Agency for Research on Cancer, 2010. Available from: http: //globocan.iarc.fr. Lyon, France, 2010. Guyomard 2007 Guyomard V, Leinster S, Wilkinson M. Systematic review of studies of patients satisfaction with breast reconstruction after mastectomy. Breast 2007;16(6):54767. [PUBMED: 18024116] Harcourt 2001 Harcourt D, Rumsey N. Psychological aspects of breast reconstruction: a review of the literature. Journal of Advanced Nursing 2001;35(4):47787. [PUBMED: 11529946] Higgins 2003 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327 (7414):55760. Higgins 2008 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 [updated February 2008]. The Cochrane Collaboration, 2008. Available from www.cochrane-handbook.org. The Cochrane Collaboration. Hussien 2004 Hussien M, Salah B, Malyon A, Wieler-Mithoff EM. The effect of radiotherapy on the use of immediate breast reconstruction. European Journal of Surgical Oncology 2004; 30(5):4904. [PUBMED: 15135475] Jemal 2009 Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer Statistics, 2009. CA: A Cancer Journal for Clinicians 2009; 59(4):22549. Kronowitz 2004 Kronowitz SJ, Hunt KK, Kuerer HM, Babiera G, McNeese MD, Buchholz TA, et al.Delayed-immediate breast reconstruction. Plastic and Reconstructive Surgery 2004;113 (6):1617-28. Kronowitz 2009 Kronowitz SJ, Robb GL. Radiation therapy and breast reconstruction: a critical review of the literature. Plastic and Reconstructive Surgery 2009;124(2):395408. [PUBMED: 19644254] Krueger 2001 Krueger EA, Wilkins EG, Strawderman M, Cederna P, Goldfarb S, Vicini FA, et al.Complications and patient satisfaction following expander/implant breast reconstruction with and without radiotherapy. International Journal of Radiation Oncology, Biology, Physics 2001;49(3): 71321. Langstein 2003 Langstein HN, Cheng MH, Singletary SE, Robb GL, Hoy E, Smith TL, et al.Breast cancer recurrence after immediate reconstruction: patterns and signicance. Plastic and Reconstructive Surgery 2003; Vol. 111, issue 2:712-20. Mandrekas 1995 Mandrekas AD, Zambacos GJ, Katsantoni PN. Immediate and delayed breast reconstruction with permanent tissue expanders. British Journal of Plastic Surgery 1995;48(8): 5728. [PUBMED: 8548159] McCarthy 2005 McCarthy CM, Pusic AL, Disa JJ, McCormick B, Montgomery LL, Cordeiro PG. Unilateral postoperative chest wall radiotherapy in bilateral tissue expander/implant reconstruction patients: a prospective outcomes analysis. Plastic and Reconstructive Surgery 2005;116:16427. Newman 1999 Newman LA, Kuerer HM, Hunt KK, Ames FC, Ross MI, Theriault R, et al.Feasibility of immediate breast reconstruction for locally advanced breast cancer. Annals of Surgical Oncology 1999; Vol. 6, issue 7:671-5. Ofce for National Statistics 2009 Cancer Registration Statistics England 2006. Ofce for National Statistics (ONS) 2006 (Accessed 01.07.2010). [DOI: http://info.cancerresearchuk.org/cancerstats/ incidence/risk/?a=5441#source5] 14 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. RevMan 2008 The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008. Rogers 2002 Rogers NE, Allen RJ. Radiation effects on breast reconstruction with the deep inferior epigastric perforator ap. Plastic and Reconstructive Surgery 2002; Vol. 109, issue 6:1919-24. Schulz 1995 Schulz KF, Chalmers I, Hayes RJ. Empirical evidence of bias. JAMA 1995;273:40812. Schuster 1992 Schuster RH, Kuske RR, Young VL, Fineberg B. Breast reconstruction in women treated with radiation therapy for breast cancer: cosmesis, complications, and tumor control. Plastic and Reconstructive Surgery 1992; Vol. 90, issue 3: 445-52. Spear 2005 Spear SL, Ducic I, Low M, Cuoco F. The effect of radiation on pedicled TRAM ap breast reconstruction: outcomes and implications. Plastic and Reconstuctive Surgery 2005; 115(1):8495. Tallet 2003 Tallet AV, Salem N, Moutardier V, Ananian P, Braud AC, Zalta R, et al.Radiotherapy and immediate two-stage breast reconstruction with a tissue expander and implant: complications and esthetic results. International Journal of Radiation Oncology, Biology, Physics 2003; Vol. 57, issue 1:13642. Thomson 2008 Thomson HJ, Potter S, Greenwood RJ, Bahl A, Barker J, Cawthorn SJ, et al.A prospective longitudinal study of cosmetic outcome in immediate latissimus dorsi breast reconstruction and the inuence of radiotherapy. Annals of Surgical Oncology 2008;15(4):108191. [PUBMED: 18224376] Tran 2001 Tran NV, Chang DW, Gupta A, Kroll SS, Robb GL. Comparison of immediate and delayed free TRAM ap breast reconstruction in patients receiving postmastectomy radiation therapy. Plastic and Reconstructive Surgery 2001; 108(1):7882. von Smitten 1992 von Smitten K, Sundell B. The impact of adjuvant radiotherapy and cytotoxic chemotherapy on the outcome of immediate breast reconstruction by tissue expansion after mastectomy for breast cancer. European Journal of Surgical Oncology 1992;18(2):11923. [PUBMED: 1582504] Whelan 2000 Whelan TJ, Julian J, Wright J, Jadad AR, Levine ML. Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis. Journal of Clinical Oncology 2000; 18(6):12209. [PUBMED: 10715291] Whiteld 2009 Whiteld GA, Horan G, Irwin MS, Malata CM, Wishart GC, Wilson CB. Incidence of severe capsular contracture following implant-based immediate breast reconstruction with or without postoperative chest wall radiotherapy using 40 Gray in 15 fractions. Radiotherapy and Oncology 2009; 90(1):1417. [PUBMED: 18977547] Williams 1995 Williams JK, Bostwick J, Bried JT, Mackay G, Landry J, Benton J. TRAM ap breast reconstruction after radiation treatment. Annals of Surgery 1995; Vol. 221, issue 6:756- 64.
Indicates the major publication for the study
15 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. C H A R A C T E R I S T I C S O F S T U D I E S Characteristics of included studies [ordered by study ID] Dean 1983 Methods Randomised controlled trial in Longmore Hospital Edinburgh between October 1978 and July 1980 Participants N = 64 women, age unspecied but all under 60 years. INCLUSION CRITERIA: primary operable breast cancer (T 12 N 01 ) requiring mastectomy; no metastatic disease (normal pelvis/chest x rays, bone and liver isotope scans and liver function tests). EXCLUSION CRITERIA: over 60 years; non-operable breast cancer; metastatic disease. WITHDRAWALS/LOSSES TO FOLLOW-UP: Immediate Group: 2 withdrawals after randomisation (1) not reconstructed for technical reasons feasible, (1) had implant accidentally aspirated post-operatively Delayed Group: withdrawals (25) i.e. chose no reconstruction. Interventions Total mastectomy (with axillary node clearance for some participants), followed by im- mediate reconstruction compared with an option of delayedreconstruction at 12 months INTERVENTION: (31/33) sialastic subpectoral prosthesis (Heyer-Schultz). Post -op care: penicillin V (1 gm/day) and ucloxacillin (1 gm/day) orally for 5 days. Participants with positive nodes received radiotherapy, node-positive and premenopausal received chemotherapy or oophorectomy CONTROL: (6/31) opted for delayed reconstruction. Outcomes PRIMARY OUTCOMES: No post-operative morbidity or mortality was reported. SECONDARY OUTCOMES: cosmetic appearance assessed at 9 to 17 months by investigators and panel of assessors (3-point scale: 5 = good, 3 = average, 1 = poor); psychological assessments by interview at 3 and 12 months, psychiatric, sexual, social, marital, and work morbidity; participants completed a general health questionnaire. ADVERSEEVENTS: No reporting of long termpost-op complications or adverse events Notes The comparisons were mastectomy with immediate reconstruction versus mastectomy and optional delayed reconstruction. Unclear if the evaluations included the 6/31 in the delayed reconstruction (12 months post mastectomy) group Risk of bias 16 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Dean 1983 (Continued) Bias Authors judgement Support for judgement Random sequence generation (selection bias) Unclear risk Quote: were randomly allocated The patient was then randomised in the oper- ating room to either receive an implant or not. were randomly selected.... Pg 459. Comment: Insufcient information in the report about the method use to generate the allocation sequence Allocation concealment (selection bias) Unclear risk The method used to conceal the allocation sequence, that is to determine whether in- terventionallocations couldhave beenfore- seen in advance of, or during enrolment, was not reported. Comment: Insufcient informationto per- mit judgement Yes or No Blinding (performance bias and detection bias) All outcomes High risk Participants: not possible to blind. Healthcare providers: not possible to blind. Outcomes assessors and data analysts: un- clear who were the outcomes assessors, but at least some were investigators. Unclear if the data analysts were blinded Incomplete outcome data (attrition bias) All outcomes High risk 2 participants (implant group) were not seen for pre-operative psychiatric assess- ments. No post -operative data for the delayed re- constructiongroup(6/31), andmissing fol- low-up data for 4 participants in the im- mediate reconstruction group. Cosmetic appearance of patients with im- plants assessments at 9 to 17 months, un- clear whether this data includedthe delayed implant group (6). General HealthQuestionnaire: Incomplete data 14/64 (22%) at followup, but unclear from which group and the reasons. Data analysis did not conformto ITTprin- ciples. Selective reporting (reporting bias) Low risk The stated objectives of the study appeared to match the reported outcomes Other bias High risk Possible sampling bias at enrolment. Ran- domisation to reconstruction or no recon- struction occurred after the mastectomy 17 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Dean 1983 (Continued) procedure, the possibility of selection bias cannot be ruled out ITT: intention-to-treat Characteristics of excluded studies [ordered by study ID] Study Reason for exclusion Alderman 2002 Non RCT, prospective cohort. Atisha 2009 Non RCT, retrospective. Cheng 2006 Non RCT. Fernandez-Delgado 2008 Non RCT, questionnaire. Harcourt 2003 Non RCT. Neyt 2005 Non RCT. Roth 2007 Non RCT. Wilkins 2000 Non RCT, prospective cohort study. RCT: randomised controlled trial 18 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. D A T A A N D A N A L Y S E S Comparison 1. Immediate versus delayed reconstruction Outcome or subgroup title No. of studies No. of participants Statistical method Effect size 1 Data that cannot be presented graphically in Revman Other data No numeric data Analysis 1.1. Comparison 1 Immediate versus delayed reconstruction, Outcome 1 Data that cannot be presented graphically in Revman. Data that cannot be presented graphically in Revman Study Participants Interventions Outcomes Notes Dean 1983 64 women, <60yrs, Primary operable breast cancer (T 1,2 N 0,1 ) Total mastectomy and im- mediate reconstruction ver- sus the option of delayed re- construction (12 months) INTERVENTION: (33) Sialastic prosthesis. CONTROL: (31) offered delayed reconstruction, 6 accepted. WITHDRAWALS DUE TO PROTOCOL DEVIA- TION: (25) delayed reconstruction group PRIMARY OUTCOMES: Not addressed. SECONDARY OUTCOMES: Participant assessed cosmetic evaluations (Ugly/ not ugly/almost normal) at 3 and 12 months of those who received immediate implants and control. See Table 1. No data re- ported for (6) participants with delayed reconstruction Cosmetic appearance (investigator assessed). Psychological assessments by interview at 3 and 12 months, psychiatric, sexual, social, marital, and work morbidity. General health questionnaire (participant assessed) AD- VERSE EVENTS: No post operative adverse events re- ported. Our primary outcome was not addressed, secondary outcomes of patient cos- metic evaluations and psy- chosocial well-being post- reconstruction were inade- quately reported 19 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. A D D I T I O N A L T A B L E S Table 1. Participants cosmetic evaluations at 3 and 12 months Assessment 3 months 12 months Implant No implant Implant No Implant Ugly 11 20 8 17 Not ugly 11 8 21 11 Almost Normal 8 2 2 1 Total 30 30 31 29 64 randomised: 31 immediate reconstruction, 6/33 delayed reconstruction (Data inconsistently unreported) Table 2. Research recommendations based on a gap in the evidence of immediate versus delayed reconstruction following surgery for breast cancer Core elements Issues to consider Status of research for this review Evidence (E) What is the current state of evidence? Asystematic reviewfound very limited reliable evidence for the benets or harms of immediate compared with delayed reconstruction following surgery for breast can- cer Population (P) Diagnosis, disease stage, comorbidity, risk factor, sex, age, ethnic group, specic inclusion or exclusion crite- ria, clinical setting Any age group with a diagnosis of primary operable breast cancer requiring mastectomy, without evidence of metastatic disease (normal pelvis/chest x-rays, bone and liver isotope scans and liver function tests) Exclusion criteria: non-operable breast cancer, metastatic disease. To limit geographical and cultural biases and ensure a wider generalisability of the evidence, greater empha- sis should be placed on a more culturally diverse pop- ulation and which may include multi-centred interna- tional settings for future studies Intervention (I) Type, frequency, dose, duration, prognostic factor Total mastectomy (with/without axillary node clear- ance), followed by immediate reconstruction with an autologous ap and/or any other form of implant Comparison (C) Type, frequency, dose, duration, prognostic factor Delayed reconstruction at 12 months. Outcome (O) Which clinical or patient related outcomes will the re- searcher need to measure, improve, inuence or accom- Clinical outcomes: mortality, 20 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Table 2. Research recommendations based on a gap in the evidence of immediate versus delayed reconstruction following surgery for breast cancer (Continued) plish? Which methods of measurement should be used? intra and post operative complications/adverse events. Patient-preferred outcomes: quality of life, emotional and psychological morbidity, cosmetic appearance (assessed with validated generic or disease-specic assessment tools). Time Stamp (T) Date of literature search or recommendation EMBASE and Medline till 26th August 2010, ICTRP and Cochrane Breast Cancer Groups Specialised Reg- ister till 22nd July 2010 Study Type What is the most appropriate study design to address the proposed question? Randomised controlled trial (adequately powered) with up to a 5 year follow-up Methods: concealment of allocation sequence Blinding: Not possible to blind participants or care givers but outcomes assessors and data analysts should be blinded Setting: Specialised surgical/ plastic surgery unit. A P P E N D I C E S Appendix 1. MEDLINE search strategy (via Ovid) 1. randomised controlled trial.pt. 2. controlled clinical trial.pt. 3. randomized.ab. 4. randomised.ab 5. placebo.ab. 6. randomly.ab. 7. trial.ab. 8. groups.ab. 9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 10. exp Breast Neoplasms/ 11. (breast adj6 cancer$).mp. 12. (breast adj6 neoplasm$).mp. 13. (breast adj6 carcinoma$).mp. 14. (breast adj6 tumour$).mp. 15. (breast adj6 tumor$).mp. 16. 10 or 11 or 12 or 13 or 14 or 15 17. exp Reconstructive Surgical Procedures/ 18. exp Breast Implants/ 19. exp Prostheses and Implants/ 20. exp Mammaplasty/ 21. exp Surgical Flaps/ 22. (breast adj6 reconstruct$).mp. 21 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 23. (breast adj6 reconstruct$ adj6 surger$).mp. 24. (breast adj6 reconstruct$ adj6 surgical adj6 procedure$).mp. 25. (immediate$ adj6 breast adj6 reconstruct$).mp. 26. (immediate$ adj6 breast adj6 reconstruct$ adj6 surger$).mp. 27. (immediate$ adj6 breast adj6 reconstruct$ adj6 surgical adj6 procedure$).mp. 28. (delay$ adj6 breast adj6 reconstruct$).mp. 29. (delay$ adj6 breast adj6 reconstruct$ adj6 surger$).mp. 30. (delay$ adj6 breast adj6 reconstruct$ adj6 surgical adj6 procedure$).mp. 31. 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 32. exp Mastectomy/ 33. (post$ adj6 mastectom$).mp. 34. 32 or 33 35. 9 and 16 and 31 and 34 36. limit 35 to humans Appendix 2. EMBASE Search Strategy (Ovid SP format) 1. exp breast cancer/ 2. breast tumor/ 3. exp neoplasm/ and medullary.mp. 4. exp brocystic breast disease/ 5. 1 or 2 or 4 or 3 6. exp breast/ 7. breast.tw. 8. 7 or 6 9. (breast adj milk).ti,ab,sh. 10. (breast adj tender$).ti,ab,sh. 11. 9 or 10 12. 8 not 11 13. exp neoplasm/ 14. 12 and 13 15. exp lymphedema/ 16. 14 and 15 17. (breast adj25 neoplasm$).ti,ab,sh. 18. (breast adj25 cancer$).ti,ab,sh. 19. (breast adj25 tumour$).ti,ab,sh. 20. (breast adj25 tumor$).ti,ab,sh. 21. (breast adj25 carcinoma$).ti,ab,sh. 22. (breast adj25 adenocarcinoma$).ti,ab,sh. 23. (breast adj25 sarcoma$).ti,ab,sh. 24. (breast adj25 dcis).ti,ab,sh. 25. (breast adj25 ductal).ti,ab,sh. 26. (breast adj25 inltrating).ti,ab,sh. 27. (breast adj25 intraductal).ti,ab,sh. 28. (breast adj25 lobular).ti,ab,sh. 29. (breast adj25 medullary).ti,ab,sh. 30. or/17-29 31. 5 or 14 or 30 or 16 32. exp mastectomy/ 33. 31 or 32 34. exp mammary neoplasms/ 35. (mammary adj25 neoplasm$).ti,ab,sh. 22 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 36. (mammary adj25 cancer$).ti,ab,sh. 37. (mammary adj25 tumour$).ti,ab,sh. 38. (mammary adj25 tumor$).ti,ab,sh. 39. (mammary adj25 carcinoma$).ti,ab,sh. 40. (mammary adj25 adenocarcinoma$).ti,ab,sh. 41. (mammary adj25 sarcoma$).ti,ab,sh. 42. (mammary adj25 dcis).ti,ab,sh. 43. (mammary adj25 ductal).ti,ab,sh. 44. (mammary adj25 inltrating).ti,ab,sh. 45. (mammary adj25 intraductal).ti,ab,sh. 46. (mammary adj25 lobular).ti,ab,sh. 47. (mammary adj25 medullary).ti,ab,sh. 48. or/34-47 49. 33 or 48 50. (breast adj6 reconstruct$).mp. 51. (breast adj6 reconstruct$ adj6 surger$). ti,ab,sh. 52. (breast adj6 reconstruct$ adj6 surgical adj6 procedure$). ti,ab,sh. 53. (immediate$ adj6 breast adj6 reconstruct$). ti,ab,sh. 54. (immediate$ adj6 breast adj6 reconstruct$ adj6 surger$). ti,ab,sh. 55. (immediate$ adj6 breast adj6 reconstruct$ adj6 surgical adj6 procedure$). ti,ab,sh. 56. (delay$ adj6 breast adj6 reconstruct$). ti,ab,sh. 57. (delay$ adj6 breast adj6 reconstruct$ adj6 surger$). ti,ab,sh. 58. (delay$ adj6 breast adj6 reconstruct$ adj6 surgical adj6 procedure$). ti,ab,sh. 59. or/50-58 60. 49 and 59 61. exp controlled clinical trial/ 62. comparative study/ 63. drug comparison/ 64. randomization/ 65. crossover procedure/ 66. double blind procedure/ 67. single blind procedure/ 68. placebo/ 69. prospective study/ 70. ((clinical or controlled or comparative or placebo or prospective or randomi#ed) adj3 (trial or study)).ti,ab. 71. (random$ adj7 (allocat$ or allot$ or assign$ or basis$ or divid$ or order$)).ti,ab. 72. ((singl$ or doubl$ or trebl$ or trip$) adj7 (blind$ or mask$)).ti,ab. 73. (cross?over$ or (cross adj1 over$)).ti,ab. 74. or/61-73 75. 60 and 74 76. limit 75 to human 77. limit 76 to yr=2003 - 2010 23 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Appendix 3. WHO ICTRP Search WHO ICTRP Search (22/07/2010) 1. Title: breast reconstruction ORimmediate breast reconstruction OR immediate reconstruction ORdelay* breast reconstruction OR delay* reconstruction OR postmastectomy OR postmastectomies OR post mastectomy OR post mastectomies OR post-mastectomy OR post-mastectomies OR Latissimus Dorsi Myocutaneous Flap OR Latissimus Dorsi Myocutaneous Flaps OR TRAM Flap OR TRAM Flaps OR Deep Inferior Epigastric Perforator Flap OR Deep Inferior Epigastric Perforator Flaps OR DIEP Flap OR DIEP Flaps ORGluteal Artery Perforator ORGAP ORTransverse Rectus Abdominus Myocutaneous Flap ORTransverse Rectus Abdominus Myocutaneous Flaps Condition: breast cancer OR breast cancers OR breast carcinoma OR breast carcinomas OR breast neoplasm OR breast neoplasms OR ductal carcinoma in situ OR DCIS 2. Condition: breast cancer OR breast cancers OR breast carcinoma OR breast carcinomas OR breast neoplasm OR breast neoplasms OR ductal carcinoma in situ OR DCIS Intervention: breast reconstruction OR immediate breast reconstruction OR immediate reconstruction OR delayed breast reconstruc- tion OR delayed reconstruction OR postmastectomy OR postmastectomies OR post mastectomy OR post mastectomies OR post- mastectomy OR post-mastectomies OR Latissimus Dorsi Myocutaneous Flap OR Latissimus Dorsi Myocutaneous Flaps OR TRAM Flap OR TRAM Flaps OR Deep Inferior Epigastric Perforator Flap OR Deep Inferior Epigastric Perforator Flaps OR DIEP Flap OR DIEP Flaps OR Gluteal Artery Perforator OR GAP OR Transverse Rectus Abdominus Myocutaneous Flap OR Transverse Rectus Abdominus Myocutaneous Flaps W H A T S N E W Last assessed as up-to-date: 25 August 2010. Date Event Description 9 July 2011 Amended Correctied minor topographical errors. H I S T O R Y Protocol rst published: Issue 9, 2010 Review rst published: Issue 7, 2011 C O N T R I B U T I O N S O F A U T H O R S Nigel DSouza (ND), Geraldine Darmanin (GD) and Zbys Fedorowicz (ZF) were responsible for: organising the retrieval of papers; writing to authors of papers for additional information; data collection for the review; obtaining and screening data on unpublished studies. ZF and ND were responsible for entering any extracted data into RevMan. ZF and ND were responsible for the analysis and interpretation of data. 24 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ND and ZF were responsible for: screening search results; screening retrieved papers against inclusion criteria; appraising the quality of papers; extracting data from papers; designing the review; co-ordinating the review; and data management for the review. All review authors contributed to writing the review. ND is the guarantor for the review. D E C L A R A T I O N S O F I N T E R E S T There are no nancial conicts of interest and the authors declare that they do not have any associations with any parties who may have vested interests in the results of this review. S O U R C E S O F S U P P O R T Internal sources Cochrane Breast Cancer Group, Australia. External sources No sources of support supplied D I F F E R E N C E S B E T W E E N P R O T O C O L A N D R E V I E W In viewof the lownumber of studies eligible for inclusion we considered those studies in which immediate reconstruction was compared with the option of delayed or no treatment. I N D E X T E R M S 25 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Medical Subject Headings (MeSH) Breast Neoplasms [psychology;
surgery]; Mammaplasty [
methods; psychology]; Randomized Controlled Trials as Topic; Time Factors
MeSH check words Female; Humans 26 Immediate versus delayed reconstruction following surgery for breast cancer (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.