Oncoplastic breast‐conserving surgery for women with primary breast cancer

Objectives

This is a protocol for a Cochrane Review (intervention). The objectives are as follows:

• To assess the oncological control of oncoplastic breast‐conserving surgery for women with breast cancer.

• To assess patient satisfaction through patient‐reported outcomes, surgical complications, need for further surgery to achieve adequate oncological resection and cosmetic outcomes through objective measures or clinician‐reported outcomes.

• To summarise the use of different oncoplastic techniques and determine the selection criteria if reported.

Background

Description of the condition

Breast cancer is the most commonly diagnosed cancer in women worldwide in low‐, middle‐ and high‐income countries (Bray 2018). Globally, the incidence rates are increasing but the mortality rates are decreasing with improved treatments, leaving many more breast cancer survivors (WHO 2010). For example, in the UK an estimated 691,000 women are alive after a diagnosis of breast cancer and this is predicted to rise to 840,000 women in 2020 (Breast Cancer Care 2020). There are over 3.8 million breast cancer survivors in the USA, including those who have finished treatment or are in the process of receiving treatment (BCRF 2019).

For the majority of women with early breast cancer, the first treatment is breast surgery with curative intent (Breast Cancer Care 2020). As survival improves following breast cancer treatment, it has become imperative to improve quality of life, and long‐term appearance and aesthetic outcomes after surgery have become increasingly relevant.

Description of the intervention

Surgery for breast cancer has evolved considerably over the years, from the radical mastectomy of Halsted 1894 to the development and acceptance of breast‐conserving therapy as standard of care in recent years. Breast‐conserving surgery (BCS) usually refers to lumpectomy or wide local excision (WLE). BCS followed by radiotherapy has been found to be equivalent in disease‐free and overall survival when compared with mastectomy and hence has become the standard of care for early‐stage breast cancer (Agarwal 2014; Fisher 2002; Van Maaren 2016; Vila 2015). A WLE may be difficult for patients with a large tumour‐to‐breast‐size ratio, resulting in poor cosmetic outcomes or patients may opt for a simple mastectomy (that is, the removal of the breast tissue up to the chest wall) (Regano 2009). There is a large variation across countries in their rates of BCS (Munzone 2014; Sun 2018).

The primary goal of oncological surgery is cancer resection: that is, where the tumour along with a margin of normal tissue is excised. There is also, however, increasing awareness that aesthetic outcomes of these procedures are extremely important. Patient expectations are increasing as they become aware that they need not be left with deformities after breast cancer surgery. Good aesthetic outcomes have been linked with significant improvements in patient satisfaction and quality of life (Kim 2015; Waljee 2008).

There are many breast reconstruction options for aesthetic improvement. Women being offered a mastectomy have the option of full breast reconstruction using either implants or their own (autologous) tissue. Breast reconstruction can be done at the same time as the mastectomy (one‐stage) or as a separate operation (two‐stage). For women undergoing BCS for large tumours, the options include either partial volume displacement or volume replacement techniques using either implants or autologous tissue (ACS 2016).

Oncoplastic breast‐conserving surgery (O‐BCS) is the term used for oncological resection (breast tumour excisions) combined with plastic surgery techniques (Almasad 2008; Clough 2003; Rainsbury 2007; Regano 2009). O‐BCS can be broadly divided into the two fundamentally different techniques.

• Volume displacement technique uses breast tissue (glandular or dermoglandular) from the same breast and places (redistributes) it into the surgical site (also known as mammoplasty).

• Volume replacement technique uses tissue other than the breast (autologous tissues) to compensate for volume loss after breast tumours have been excised.

The uniting principle of these two techniques is to conserve the breast shape/size.

Partial volume displacement techniques can include various techniques (Holmes 2011), for example:

• wise pattern therapeutic mammaplasty;

• vertical scar mammaplasty (and its variations);

• circumareolar/Benelli’s/round block mammoplasty;

• racquet handle/lateral mammaplasty.

Similarly, there are many techniques for autologous partial volume replacement techniques. The following techniques are recognised as partial volume replacement techniques where the differentiating factor between which flap is used is usually the location of the tumour.

• Defects in the lower aspects of the breast can be addressed using local flaps such as:

  • abdominal adipo‐fascial flaps (Kijima 2014; Ogawa 2007);

  • thoraco‐epigastric flaps (Hamdi 2014; Kijima 2011; Takeda 2005);

    • superior epigastric artery perforator flap (SEAP);

    • medial intercostal artery perforator (M‐ICAP);

    • internal mammary artery perforator (IMAP);

    • anterior intercostal artery perforator (A‐ICAP).

• Defects in the lateral half of the breast can be reconstituted with lateral chest wall perforator flaps such as:

  • lateral intercostal artery perforator (LICAP) (Hamdi 2006; Hu 2018);

  • lateral thoracic artery perforator (LTAP) (McCulley 2015);

  • thoracodorsal artery perforator flap (TDAP) (Munhoz 2011).

• Defects in any breast quadrant can be addressed using distant flaps. Most often these are pedicled flaps but free flaps could also be used for partial breast reconstruction such as:

  • mini‐latissimus dorsi (mini‐LD) (Raja 1997);

  • omental flaps (Zaha 2014);

  • other free flaps for partial breast reconstruction e.g. transverse gracilis (TUG) flaps (McCulley 2011).

Many early‐stage breast cancers can be successfully treated by WLE; however, the lesions with large tumour‐to‐breast‐size ratio remain a challenge for breast surgeons to treat with BCS alone. O‐BCS allows the excision of tumours that cannot be excised by—or would result in poor cosmetic outcomes from—standard BCS. It allows these women to avoid mastectomy.

In this Cochrane Review, we will compare any O‐BCS technique to other surgical techniques used for breast cancer surgery because any of the aforementioned techniques may be offered to women with breast cancer under varying circumstances. For small cancers, it is likely that WLE with or without partial reconstruction (using either autologous tissue or an implant) will be offered. In contrast, for large cancers the options could include WLE with or without partial reconstruction; or mastectomy with or without reconstruction.

How the intervention might work

For women with early‐stage breast carcinoma, studies have shown that there is no detectable difference in overall survival or disease‐free survival in those who have breast‐conserving surgery plus radiotherapy and those who have mastectomy (Poggi 2003; Van Maaren 2016). There has been an increased adoption of the practice in many countries to facilitate breast‐conserving therapy and avoid unnecessary mastectomies (Kaufman 2019). The emphasis remains on safe and adequate cancer resection whilst aiming to achieve better aesthetic outcomes to improve quality of life.

There is evidence indicating that cosmesis, patient satisfaction and quality of life improve with breast‐conserving surgery compared to mastectomy (Kim 2015; Waljee 2008). The options for surgical resection for breast cancer are dictated by the size of the tumour. There is an indirect correlation between the percentage of breast volume excised and cosmesis, which can have an impact on the satisfaction levels after BCS (Cochrane 2003). O‐BCS techniques aim to keep the breast shape and size similar despite oncological resection; therefore it would be logical to expect better patient satisfaction.

Why it is important to do this review

Although oncoplastic surgery has rapidly gained acceptance and is widely practised, cohesive evidence is still lacking on both the short‐term and long‐term outcomes, particularly for partial breast reconstruction.

Since the most recent systematic review of oncoplastic breast surgery concluded its search in 2015 (Yiannakopoulou 2016), there have been over 30 articles published regarding partial breast reconstruction. A summary of evidence from this literature will help clinicians understand the indications and clinical, oncological and cosmetic outcomes of such techniques. This Cochrane Review will update our understanding of this rapidly evolving area of clinical practice and address the questions unexplored by previous reviews. In addition, this review will focus on volume displacement and replacement techniques as separate subsets of O‐BCS and compare these techniques with other alternatives.

Objectives

• To assess the oncological control of oncoplastic breast‐conserving surgery for women with breast cancer.

• To assess patient satisfaction through patient‐reported outcomes, surgical complications, need for further surgery to achieve adequate oncological resection and cosmetic outcomes through objective measures or clinician‐reported outcomes.

• To summarise the use of different oncoplastic techniques and determine the selection criteria if reported.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs) assessing oncoplastic breast‐conserving surgery. We anticipate, however, that there will be few or no RCTs on the topic. We will therefore expand the inclusion criteria to include comparative non‐randomised studies (i.e. cohort studies, case‐control studies and prospectively designed patient registries) that include 20 or more women with oncoplastic breast‐conserving surgery.

We will include studies published in English from 1980 onwards as this is the date at which partial breast reconstruction was introduced.

We will exclude single‐arm studies, expert opinion and duplicate studies.

Types of participants

We will include women with primary breast cancer who have undergone any oncoplastic breast‐conserving surgery using either partial volume displacement or replacement breast reconstruction for cancer.

We will exclude men and people who have undergone surgery for benign breast conditions.

Types of interventions

Experimental interventions

Any oncoplastic breast‐conserving surgery techniques including:

• Volume displacement techniques

• • wise pattern therapeutic mammaplasty

  • vertical scar mammaplasty (and its variations)

  • circumareolar/Benelli’s/Round block mammoplasty

  • racquet handle/lateral mammaplasty

• Volume replacement techniques

• • abdominal adipo‐fascial flaps/advancement flaps

  • lateral chest wall perforator flaps

    • lateral intercostal artery perforator flap (LICAP)

    • lateral thoracic artery perforator (LTAP)

    • thoracodorsal artery perforator flap (TDAP)

  • latissimus dorsi mini‐flap (LD)

  • thoraco‐epigastric Flaps

    • superior epigastric artery perforator flap (SEAP)

    • medial intercostal artery perforator (M‐ICAP)

    • internal mammary artery perforator (IMAP)

    • anterior intercostal artery perforator (A‐ICAP)

  • omental flaps

  • free flaps for partial breast reconstruction

We will include other techniques if mentioned in the literature.

Comparator interventions

Any other surgical treatment. The comparators will be stratified into partial resection and mastectomy. These include:

• wide local excision (WLE);

• partial volume replacement using non‐autologous tissue;

• mastectomy with no reconstruction;

• mastectomy with breast reconstruction using an implant alone;

• mastectomy with breast reconstruction using autologous tissue including pedicled and free flaps.

The main analysis will be any O‐BCS versus WLE and any O‐BCS versus mastectomy without any and then with breast reconstruction procedures.

Co‐interventions

We recognise that some women with breast cancer may also undergo hormonal therapy, chemotherapy or radiotherapy, or a combination of therapies. We will collect data on whether patient received these co‐interventions; we do not, however, plan on conducting a subgroup analysis.

Types of outcome measures

Primary outcomes

The primary outcomes will focus on oncological control by oncoplastic breast‐conserving surgery by assessing:

• loco‐regional recurrence (that is, ipsilateral breast tumour recurrence), defined as cancer detected in the same breast where the cancer had been diagnosed;

• breast‐cancer‐specific disease‐free survival, defined as the time from the date of completing initial treatment (that is, completing the surgical procedure) to the first date of a local, regional, or distant relapse, diagnosis of a second primary breast cancer, or death due to this; and

• overall survival, defined as the time from date of randomisation to death from any cause, or number of deaths from any cause.

Follow‐up will be one year and five years if reported as dichotomous outcomes; or longest reported follow‐up if hazard ratios are reported.

Secondary outcomes

The secondary outcomes will focus on oncological, surgical and cosmetic outcomes by assessing:

• Patient‐reported outcome measures, such as patient satisfaction, that derive from validated questionnaires (for example, Breast‐Q (Cohen 2016);

• Need for further breast surgery due to inadequate cancer resection (for example, re‐excision for further margin resection or completion mastectomy);

• Surgical complications, for example flap necrosis, infection, wound dehiscence and any other complications reported in the literature;

• Recall rates, defined as abnormal surveillance on mammogram resulting in additional imaging or biopsy;

• Need for further surgery to address aesthetics or symmetry (for example, symmetrisation or fat transfer); and

• Surgeon‐reported cosmetic outcomes that derive from subjective or objective validated scales (for example, the Harris scale and Breast Analyzing Tool (Harris 1979; Krois 2017)).

Search methods for identification of studies

Electronic searches

We will search the following databases.

• The Cochrane Breast Cancer's Specialised Register. Details of the search strategies used by the Group for the identification of studies and the procedure used to code references are outlined on the Group's website (breastcancer.cochrane.org/sites/breastcancer.cochrane.org/files/public/uploads/specialised_register_details.pdf). We will extract trials with the following key words and consider them for inclusion in the review: abdominal adipo‐fascial flaps, lateral chest wall perforator flaps, lateral intercostal artery perforator flap, latissimus dorsi mini‐flap, omental flaps, thoraco‐epigastric flaps, superior epigastric artery perforator flap, medical intercostal artery perforator, internal mammary artery perforator, anterior inter‐costal artery perforator, advancement/random pattern or rotation flaps, free flaps for partial breast reconstruction, breast‐conserving surgery, oncoplastic breast surgery, partial volume replacement breast, partial breast reconstruction and partial mastectomy. We will search for papers including women with breast cancer who are undergoing any kind of oncoplastic breast‐conserving surgery as it is often the case for breast‐conserving surgeries to be grouped together.

• CENTRAL (in the Cochrane Library, latest issue). See Appendix 1.

• MEDLINE (via Ovid SP) from 1980 to present. See Appendix 2.

• Embase (via Ovid SP) from 1980 to present. See Appendix 3.

• The World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (apps.who.int/trialsearch/Default.aspx) for all prospectively registered and ongoing trials. See Appendix 4.

• ClinicalTrials.gov. See Appendix 5.

Searching other resources

Bibliographic searching

We will screen the studies in the reference lists of identified relevant trials or reviews (for example: Chen 2018;De La Cruz 2016; Haloua 2013; Losken 2014; Yoon 2016). We will obtain a copy of the full‐text article for each reference reporting a potentially eligible study. Where this is not possible, we will try to contact authors for additional information.

Data collection and analysis

Selection of studies

We will upload references into Covidence. Two review authors (AN and JH) will independently examine each title and abstract to determine whether reports appear to meet the inclusion criteria based on the protocol, and resolve any differences by discussion. We will obtain copies of potentially eligible reports and two review authors (AN and JH) will examine the full‐text articles independently. We will use Cochrane Task Exchange to help with translations, if necessary. We will place potentially relevant studies that we are unable to translate in the ‘Studies awaiting classification’ section. The review author team will review all potentially eligible reports and decide which studies should be included in the review. We will record the selection process in a PRISMA flow diagram; we will record excluded studies in the 'Characteristics of excluded studies' table.

Data extraction and management

The review author team will design and agree upon the uniform criteria for data extraction and create a standardised form in Excel prior to review commencement. Two review authors (AN and JH) will independently undertake data extraction and will resolve any differences by discussion, or consult a third review author (PR) to help resolve any disagreements. For those studies with more than one publication, we will extract data from all publications and consider the version with the longest follow‐up as the primary reference for the study.

We will tabulate the study characteristics for each included study to determine whether we are able to synthesise these data and present them in text or tabular form. We will include the following information from the individual studies on standardised data extraction forms.

• General Information

  • Author names, countries and year of publication

  • Study design and level of evidence

  • Conflicts of interest and funding

• Demographics

  • Number of participants

  • Number of breasts treated

  • Age of participants

  • Smoking history

  • History of diabetes

  • History of steroid intake or immunosuppression

  • BMI

• Breast factors

  • Preoperative breast/bra size

  • Oncological parameters

    • Type of cancer (invasive or in situ)

    • Grade

    • Stage

    • Axillary nodal status

    • Hormone receptor status (oestrogen receptor, progesterone receptor), HER2 status

    • Size of tumour including any associated additional foci

    • Location of tumour (which quadrant)

  • Tumour–nipple distance

    • Solitary, multifocal or multicentric

    • Presence of lymphovascular invasion

• Cancer treatment

  • Adjuvant radiotherapy

  • Prior neoadjuvant or adjuvant chemotherapy

  • Previous breast surgery

• Technical surgical details

  • Incision used

  • Reconstruction performed

  • Flap included a skin paddle used to reconstruct a skin defect

• Post‐surgical details

  • Median follow‐up duration

  • Loss to follow‐up expressed as a percentage

• Primary outcomes as described above

  • Local recurrence

  • Survival (for example, disease‐specific (breast cancer) and overall survival)

• Secondary outcomes as described above

  • Patient‐reported outcome measures (for example, patient satisfaction)

  • Need for further breast surgery due to inadequate cancer resection

  • Surgical complications

  • Recall rates

  • Need for further surgery to address aesthetics/symmetry

  • Surgeon‐reported cosmetic outcomes

• Surgical outcomes

  • Early complications, for example:

    • completion mastectomy rates

    • flap necrosis

    • infection

    • re‐admission

    • generic surgical complications

  • Late complications, for example:

    • correction of symmetry (contralateral augmentation/reduction or nipple reconstruction)

    • correction of deformity (lipo‐modelling, scar revision etc.)

    • any other breast procedures

• Cosmetic outcomes

  • Clinician‐reported

  • Patient‐reported outcome measures such as satisfaction and quality of life (QoL)

  • Any symmetrisation surgery

• For non‐randomised studies

  • Methods used to control for confounders

  • Adjusted and unadjusted outcome measures

  • List of variables included in analyses for adjusted estimates

The review author team will make decisions as to the presentation of data in the review and the 'Characteristics of included studies' tables. If reports relating to the same study appear in multiple publications, we will combine them under the overall study ID.

Assessment of risk of bias in included studies

We will use Cochrane's 'Risk of bias' tool for RCTs and the ROBINS‐I tool for non‐randomised studies. We will compare study protocols with final papers where possible and we will note if key information is missing across all study types.

Randomised controlled trials

We will assess risk of bias as low, high, or unclear, according to the following domains.

• Random sequence generation (selection bias)

• Allocation concealment (selection bias)

• Blinding of participants and personnel (performance bias)

• Blinding of outcome assessment (detection bias)

• Incomplete outcome data (attrition bias)

• Selective outcome reporting (reporting bias)

• Other bias

Non‐randomised studies

Two review authors (AN and SH) will apply the ROBINS‐I tool, as described in Sterne 2016, to assess risk of bias in the results of non‐randomised studies that compare health effects of two or more interventions. We will resolve disagreements by discussion. We will use the ROBINS‐I tool for cohort studies, case‐control studies and prospective patient registries. We will complete separate ROBINS‐I tables to generate an overall risk of bias for each study. For non‐randomised studies, we will assess the risk of bias according to the following domains.

Pre‐intervention bias

• Due to confounding: for example comorbidities of patients, associated DCIS, predominance of small tumour size or small tumour:breast ratio (no established cut‐offs exist for defining size), lack of pathology reporting in published literature, smoking status, age, ethnicity, genetic risk for breast cancer

• In the selection of participants into the study

At‐intervention bias

• In the classification of the intervention

• Due to surgeon technique and experience

• Due to centre‐specific experience and post‐operative follow‐up

Post‐intervention bias

• Due to deviations from the intended intervention

• Due to missing data

• In measurement of outcomes: for example cosmetic assessment being subjective and not using validated anonymised questionnaires

• In the selection of the reported results

We will score each of these domains as having low, moderate, serious, or critical risk bias. Based on these scores, we will determine an overall risk of bias for each study. If we grade any domain as serious, we will deem the overall risk of bias as serious.

When considering treatment effects, we will take into account the risk of bias for studies that contribute to each outcome.

We will summarise the 'Risk of bias’ judgements across different studies for each of the domains listed and summarise results in a 'Risk of bias’ table.

Confounding and adjustment

We will identify the confounding factors that the researchers have considered and those that have been omitted, record whether and how they have been measured and what researchers have done to control for selection bias. That is, any design features used for this purpose (for example, matching or restriction to particular subgroups) and the methods of analysis (for example, stratification, regression modelling with propensity scores or covariates). We will display as a table a list of confounders mentioned by the studies and detail how the studies dealt with them: for example restricted participant selection, demonstrated balance between groups for the confounder, matched on the confounder or adjusted for the confounder in statistical analyses to quantify the effect size.

Measures of treatment effect

We will report time‐to‐event outcomes (that is, local recurrence, overall survival) as hazard ratios (HR) with 95% confidence intervals (CIs). If necessary, we will estimate hazard ratios using the methods of Parmar 1998. If it is not possible to estimate hazard ratios from all studies, we will treat the number of events (that is, recurrences, deaths) over one year and five years of follow‐up as dichotomous outcomes.

We will set a non‐inferiority bound of less than 5% ipsilateral breast tumour recurrence at 5‐years follow‐up, as this is the same target ipsilateral breast tumour recurrence rate set for any breast conservation therapy by the Association of Breast Surgery (UK) at the British Association of Surgical Oncology (BASO) 'Surgical guidelines for the management of breast cancer' (ABS 2012).

We will report continuous outcomes (that is, patient‐reported outcome measures, quality of life) as standardised mean differences (MDs) with 95% CIs.

We will report dichotomous outcomes (that is, re‐excision rates, local or distant recurrence (if not a time‐to‐event outcome), any complications of surgery) as risk ratios (RRs) and risk differences (RDs) with 95% CIs. We will pool the data for meta‐analysis using the pooled log RR, if appropriate.

Unit of analysis issues

We anticipate that the appropriate unit of analysis will be the individual participant, rather than the surgical unit, hospital or centre.

We will exclude cross‐over and cluster‐randomised controlled trials.

Dealing with missing data

When data are missing, we will contact the study authors to request further information. When data are missing to the extent that we cannot include the study in a meta‐analysis and our attempts to retrieve data have been exhausted, we will present the results in the review and discuss in the context of the findings. We will discuss the impact of missing data and imputation methods in the 'Discussion' section of the review and when possible conduct a sensitivity analysis.

Assessment of heterogeneity

If we can combine results in a meta‐analysis, we will assess heterogeneity using the I² statistic (Higgins 2003) and interpret this according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019).

• 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*

* In cases of moderate or high heterogeneity, we will explore potential sources of heterogeneity by performing sensitivity analyses.

Assessment of reporting biases

We will search for protocols of included studies using PubMed and other trial registries, when possible. We will contact study authors to attempt to establish a full data set or reasons for the non‐reporting of certain outcomes. If more than 10 trials are included in a meta‐analysis, we plan to assess publication bias and other reporting biases by visual inspection of funnel plots for primary outcomes (Higgins 2011).

Data synthesis

If it is appropriate to perform a meta‐analysis (wherein the population, intervention, comparison and outcomes are deemed similar enough to pool), we will synthesise data using RevMan Web (RevMan Web 2019).

We will use a fixed‐effect model for data synthesis and explore the impact of model choice through sensitivity analysis.

We will analyse hazard ratios using generic inverse variance by using log odds ratios and standard errors. We will label adjustments made in individual studies within the footnotes of the forest plot.

We will summarise dichotomous outcomes using risk ratios and 95% confidence intervals (CIs); and we will summarise analyses of continuous outcomes using differences in means and 95% CIs. When different scales are used, we will summarise analyses of continuous outcomes as standardised mean differences with 95% CIs.

If the data are too diverse to permit combining of effect sizes in a meaningful or valid manner, we will present the results of individual studies in table and graphical formats and will use a narrative approach to summarise the data.

We anticipate that there will be limited scope for meta‐analysis because of the range of different outcomes measured across the small number of existing trials. In this case, we will provide a narrative synthesis of the findings from the included studies, structured around the type of intervention, target population characteristics, type of outcome and intervention content. We will follow the Cochrane guidelines for a narrative summary (Ryan 2013).

GRADE and 'Summary of findings' tables for assessing the certainty of the evidence

We will use the GRADE approach to assess the certainty of evidence of the main outcomes. We will use GRADEpro GDT software to develop the 'Summary of findings' tables. Two review authors (AN and JH) will create the 'Summary of findings' tables using the following main outcomes. We intend to have separate tables for RCTs and non‐randomised studies.

• Local recurrence at 1 year and 5 years

• Breast‐cancer‐specific disease‐free survival at 1 year and 5 years

• Patient‐reported outcome measures such as patient satisfaction

• Need for further breast surgery due to inadequate cancer resection

• Surgical complications requiring unplanned intervention

• Recall rates

• Need for further surgery to address aesthetics/symmetry

Subgroup analysis and investigation of heterogeneity

If possible, we will conduct a subgroup analysis comparing and discussing the two main techniques of oncoplastic breast‐conserving surgery — volume displacement and partial volume replacement — with any other options in breast cancer surgery. This would mean we will have the following further analyses.

• Volume displacement techniques versus WLE

• Volume displacement versus procedures involving mastectomy

• Volume replacement techniques versus WLE

• Volume replacement versus procedures involving mastectomy

If data are available, we will present one particular technique of oncoplastic breast‐conserving surgery versus any other available option for breast cancer surgery. In addition, we will present data from studies that compare the various types of flaps with each other, specifically relating to those listed in the experimental interventions section. We anticipate that most studies group the techniques together; therefore we expect few published studies. However, subgroup analysis may be possible in future reviews.

Sensitivity analysis

If adequate data are available, we will conduct the following sensitivity analyses.

• Quality assessment of included studies (removing studies that are at high risk of bias)

• Fixed‐effect model versus random‐effects model

• Missing data that require assumptions and/or imputations (removing studies where assumptions have been made)

History

Protocol first published: Issue 6, 2020

Appendices

Appendix 1. CENTRAL

#1 MeSH descriptor: [Breast Neoplasms] explode all trees
#2 breast near cancer*
#3 breast near neoplasm*
#4 breast near carcinoma*
#5 breast near tumour*
#6 breast near tumor*
#7 #1 or #2 or #3 or #4 or #5 or #6
#8 MeSH descriptor: [Mastectomy, Segmental] explode all trees
#9 (Oncoplastic breast‐conserving surgery):ti,ab,kw
#10 (Oncoplastic breast conserving surgery):ti,ab,kw
#11 (Oncoplastic breast conservation):ti,ab,kw
#12 Oncoplastic near (breast conserving or breast conservation):ti,ab,kw
#13 oncoplastic surger*:ti,ab,kw
#14 volume displacement near procedur*:ti,ab,kw
#15 volume displacement near tech*:ti,ab,kw
#16 MeSH descriptor: [Mammaplasty] explode all trees
#17 mammaplast* or mammoplast*:ti,ab,kw
#18 therapeutic near (mammaplast* or mammoplast*):ti,ab,kw
#19 Wise pattern near (mammaplast* or mammoplast*):ti,ab,kw
#20 Vertical scar near (mammaplast* or mammoplast*):ti,ab,kw
#21 Circumareolar near (mammaplast* or mammoplast*):ti,ab,kw
#22 Benelli near (mammaplast* or mammoplast*):ti,ab,kw
#23 Round block near (mammaplast* or mammoplast*):ti,ab,kw
#24 Raquet handle near (mammaplast* or mammoplast*):ti,ab,kw
#25 lateral near (mammaplast* or mammoplast*):ti,ab,kw
#26 volume replacement near procedur*:ti,ab,kw
#27 volume replacement near tech*:ti,ab,kw
#28 (Abdominal Adipo‐fascial Flap):ti,ab,kw
#29 (Abdominal Adipofascial Flap):ti,ab,kw
#30 abdominal flap*:ti,ab,kw
#31 Adipo‐fascial Flap*:ti,ab,kw
#32 Adipofascial Flap*:ti,ab,kw
#33 Thoraco‐epigastric Flap*:ti,ab,kw
#34 Thoracoepigastric Flap*:ti,ab,kw
#35 Superior epigastric artery perforator flap*:ti,ab,kw
#36 Medial Intercostal Artery Perforator flap*:ti,ab,kw
#37 Internal Mammary Artery Perforator flap*:ti,ab,kw
#38 Anterior Intercostal Artery Perforator flap*:ti,ab,kw
#39 MeSH descriptor: [Perforator Flap] explode all trees
#40 Lateral Intercostal Artery Perforator flap*:ti,ab,kw
#41 Lateral Thoracic Artery Perforator flap*:ti,ab,kw
#42 Thoracodorsal Artery Perforator Flap*:ti,ab,kw
#43 Mini Latissimus Dorsi:ti,ab,kw
#44 Omental flap*:ti,ab,kw
#45 transverse upper gracilis flap*:ti,ab,kw
#46 MeSH descriptor: [Free Tissue Flaps] explode all trees
#47 "Advancement Flap*":ti,ab,kw
#48 #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #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 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47
#49 #7 AND #48 in Trials

Appendix 2. MEDLINE

#	Searches
1	exp Breast Neoplasms/
2	(breast adj6 cancer$).tw.
3	(breast adj6 neoplasm$).tw.
4	(breast adj6 carcinoma$).tw.
5	(breast adj6 tumo?r$).tw.
6	or/1‐5
7	exp Surgical Oncology/
8	exp Breast Neoplasms/su [Surgery]
9	or/7‐8
10	6 and 9
11	exp Mastectomy, Segmental/mt [Methods]
12	Oncoplastic breast‐conserving surgery.tw.
13	Oncoplastic breast conserving surgery.tw.
14	(oncoplastic adj5 breast‐conserving adj5 surgery).tw.
15	Oncoplastic breast conservation surgery.tw.
16	(oncoplastic adj5 breast adj5 (conserving or conservation*) adj5 surgery).tw.
17	Oncoplastic breast conservation.mp.
18	(oncoplastic adj5 breast adj5 (conserving or conservation*)).tw.
19	oncoplastic surger*.tw.
20	(volume displacement and (procedur* or tech*)).tw.
21	exp Mammaplasty/
22	therapeutic mamm#plast*.mp.
23	Wise pattern therapeutic mamm#plast*.tw.
24	Vertical scar mamm#plast*.tw.
25	Circumareolar mamm#plast*.tw.
26	Benelli* mamm#plast*.tw.
27	Round block mamm#plast*.tw.
28	Raquet handle mamm#plast*.tw.
29	lateral mamm#plast*.tw.
30	(volume replacement and (procedur* or tech*)).tw.
31	Abdominal Adipo‐fascial Flap*.tw.
32	Abdominal Flap*.tw.
33	Adipo‐fascial Flap*.tw.
34	Thoraco‐epigastric Flap*.tw.
35	Superior epigastric artery perforator flap*.tw.
36	Medial Intercostal Artery Perforator flap*.tw.
37	Internal Mammary Artery Perforator flap*.tw.
38	Anterior Intercostal Artery Perforator flap*.tw.
39	exp Perforator Flap/
40	Lateral Intercostal Artery Perforator flap*.tw.
41	Lateral Thoracic Artery Perforator flap*.tw.
42	Thoracodorsal Artery Perforator Flap*.tw.
43	(mini adj5 Latissimus Dorsi).tw.
44	Omental flap*.tw.
45	transverse upper gracilis flap*.tw.
46	exp Free Tissue Flaps/
47	Advancement Flap*.tw.
48	or/11‐46
49	10 and 48
50	randomized controlled trial.pt.
51	controlled clinical trial.pt.
52	randomized.ab.
53	placebo.ab.
54	Clinical Trials as Topic/
55	randomly.ab.
56	trial.ti.
57	(crossover or cross‐over).tw.
58	Pragmatic Clinical Trials as Topic/
59	pragmatic clinical trial.pt.
60	or/50‐59
61	Case‐Control Studies/
62	Control Groups/
63	Matched‐Pair Analysis/
64	Retrospective Studies/
65	((case* adj5 control*) or (case adj3 comparison*) or control group*).ti,ab.
66	or/61‐65
67	Cohort Studies/
68	Longitudinal Studies/
69	Follow‐Up Studies/
70	Prospective Studies/
71	Retrospective Studies/
72	cohort.ti,ab.
73	longitudinal.ti,ab.
74	prospective.ti,ab.
75	retrospective.ti,ab.
76	or/67‐75
77	49 and 60
78	49 and 66
79	49 and 76
80	77 or 78 or 79
81	animals/ not humans/
82	80 not 81
83	remove duplicates from 82

Appendix 3. Embase

#	Searches
1	exp breast/
2	exp breast disease/
3	(1 or 2) and exp neoplasm/
4	exp breast tumor/
5	exp breast cancer/
6	exp breast carcinoma/
7	(breast$ adj5 (neoplas$ or cancer$ or carcin$ or tumo$ or metasta$ or malig$)).ti,ab.
8	or/3‐7
9	exp breast cancer/su [Surgery]
10	exp cancer surgery/
11	9 or 10
12	8 and 11
13	exp partial mastectomy/
14	oncoplastic breast surgery/
15	Oncoplastic breast‐conserving surgery.tw.
16	Oncoplastic breast conserving surgery.tw.
17	(oncoplastic adj5 breast‐conserving adj5 surgery).tw.
18	oncoplastic breast conservation surgery/
19	Oncoplastic breast conservation surgery.tw.
20	(oncoplastic adj5 breast adj5 (conserving or conservation*) adj5 surgery).tw.
21	Oncoplastic breast conservation.tw.
22	(oncoplastic adj5 breast adj5 (conserving or conservation*)).tw.
23	(oncoplastic adj5 (procudur* or tech* or surger*)).tw.
24	(volume displacement and (procedur* or tech*)).tw.
25	exp breast reconstruction/ and partial.tw.
26	therapeutic mamm#plast*.tw.
27	Wise pattern therapeutic mamm#plast*.tw.
28	Vertical scar mamm#plast*.tw.
29	Circumareolar mamm#plast*.tw.
30	Benelli* mamm#plast*.tw.
31	Round block mamm#plast*.tw.
32	Raquet handle mamm#plast*.tw.
33	lateral mamm#plast*.tw.
34	(volume replacement and (procedur* or tech*)).tw.
35	Abdominal Adipo‐fascial Flap*.tw.
36	Abdominal Flap*.tw.
37	exp adipofascial flap/
38	((Adipo‐fascial or adipofascial) and Flap*).tw.
39	((Thoraco‐epigastric or Thoracoepigastric) and Flap*).tw.
40	Superior epigastric artery perforator flap*.tw.
41	Medial Intercostal Artery Perforator flap*.tw.
42	Internal Mammary Artery Perforator flap*.tw.
43	Anterior Intercostal Artery Perforator flap*.tw.
44	exp perforator flap/
45	Lateral Intercostal Artery Perforator flap*.tw.
46	Lateral Thoracic Artery Perforator flap*.tw.
47	exp thoracodorsal artery perforator flap/
48	Thoracodorsal Artery Perforator Flap*.tw.
49	Mini Latissimus Dorsi.tw.
50	Omental flap*.tw.
51	transverse upper gracilis flap*.tw.
52	exp free tissue graft/
53	Advancement Flap*.tw.
54	or/13‐53
55	12 and 54
56	Randomized controlled trial/
57	Controlled clinical study/
58	Random$.ti,ab.
59	randomization/
60	intermethod comparison/
61	placebo.ti,ab.
62	(compare or compared or comparison).ti.
63	(open adj label).ti,ab.
64	((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab.
65	double blind procedure/
66	parallel group$1.ti,ab.
67	(crossover or cross over).ti,ab.
68	((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab.
69	(assigned or allocated).ti,ab.
70	(controlled adj7 (study or design or trial)).ti,ab.
71	(volunteer or volunteers).ti,ab.
72	trial.ti.
73	or/56‐72
74	exp case control study/
75	case control study.ti,ab.
76	((case control or case base or case matched or retrospective) adj1 (analys* or design* or evaulation* or research or stud* or survey* or trial*)).ti,ab.
77	or/74‐76
78	exp retrospective study/
79	exp prospective study/
80	((cohort or concurrent or incidence or longitudinal or followup or 'follow up' or prospective or retrospective) adj1 (analys* or design* or evaluation* or research or stud* or survey* or trial*)).ti,ab.
81	or/78‐80
82	55 and 73
83	55 and 77
84	55 and 81
85	82 or 83 or 84
86	limit 85 to (human and (conference abstracts or embase))
87	remove duplicates from 86

Appendix 4. WHO ICTRP

Basic search:

1. Oncoplastic breast‐conserving surger*

2. Breast cancer AND volume displacement

3. Breast cancer AND volume replacement

4. Breast cancer AND flap

Advanced search:

1. Condition: breast cancer
Intervention: oncoplastic breast surgery OR oncoplastic technique OR oncoplastic procedure
Recruitment Status: ALL

2. Condition: breast cancer
Intervention: volume displacement OR wise pattern mammaplasty OR therapeutic mammaplasty OR vertical scar mammaplasty OR Circumareolar mammoplasty OR benelli mammoplasty OR round block mammoplasty OR raquet handle mammoplasty OR lateral mammoplasty
Recruitment Status: ALL

3. Condition: breast cancer
Intervention: volume replacement OR Abdominal adipo‐fascial flap OR advancement flap OR Lateral intercostal artery perforator flap OR Lateral thoracic artery perforator OR Thoracodorsal artery perforator flap
Recruitment Status: ALL

4. Condition: breast cancer
Intervention: Latissimus dorsi mini flap OR Thoraco‐epigastric Flap OR Superior epigastric artery perforator flap OR Medial intercostal artery perforator OR Internal mammary artery perforator OR Anterior inter‐costal artery perforator OR omental flap OR transverse upper gracilis flap
Recruitment Status: ALL

Appendix 5. Clinicaltrials.gov

Basic search:

1. Condition or disease: Breast cancer
Other terms: Oncoplastic breast‐conserving surgery

2. Condition or disease: Breast cancer 
Other terms: volume displacement technique

3. Condition or disease: Breast cancer 
Other terms: volume replacement technique

4. Condition or disease: Breast cancer 
Other terms: flap (consider adding ‘reconstruction’)

Advanced search:

1. Condition or disease: Breast cancer
Intervention: Oncoplastic breast‐conserving surgery
Study type: all studies

2. Condition or disease: Breast cancer
Intervention: volume displacement technique
Study type: all studies

3. Condition or disease: Breast cancer
Intervention: therapeutic mammoplasty OR wise pattern mammoplasty OR vertical scar mammoplasty OR Circumareolar mammoplasty OR benelli mammoplasty OR round block mammoplasty OR raquet handle mammoplasty OR lateral mammoplasty
Study type: all studies

4. Condition or disease: Breast cancer
Intervention: volume replacement technique
Study type: all studies

5. Condition or disease: Breast cancer
Intervention: Abdominal Adipo‐fascial Flap OR advancement flap OR Lateral intercostal artery perforator flap OR Lateral thoracic artery perforator OR Thoracodorsal artery perforator flap 
Study type: all studies

6. Condition or disease: Breast cancer
Intervention: Latissimus dorsi mini flap OR Thoraco‐epigastric Flap OR Superior epigastric artery perforator flap OR Medial intercostal artery perforator OR Internal mammary artery perforator OR Anterior inter‐costal artery perforator OR omental flap OR transverse upper gracilis flap 
Study type: all studies

Contributions of authors

• Draft the protocol: AN, JH, SH, PGR, RR

• Study selection: AN, JH

• Extract data from studies: AN, JH

• Enter data into RevMan: AN, JH

• Carry out the analysis: AN, JH, SH, PGR

• Interpret the analysis: AN, JH, SH, PGR

• Draft the final review: AN, JH, PGR

• Disagreement resolution: PGR, RR

• Update the review: AN

Declarations of interest

Akriti Nanda: none known.
Jesse Hu: none known.
Sarah Hodgkinson: none known.
Richard Rainsbury: none known.
Pankaj Roy: none known.

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