Oncoplastic breast‐conserving surgery for women with primary breast cancer

Akriti Nanda; Jesse Hu; Sarah Hodgkinson; Sanah Ali; Richard Rainsbury; Pankaj G Roy

doi:10.1002/14651858.CD013658.pub2

. 2021 Oct 29;2021(10):CD013658. doi: 10.1002/14651858.CD013658.pub2

Oncoplastic breast‐conserving surgery for women with primary breast cancer

Akriti Nanda ¹, Jesse Hu ², Sarah Hodgkinson ³, Sanah Ali ⁴, Richard Rainsbury ⁵, Pankaj G Roy ^6,^✉

Editor: Cochrane Breast Cancer Group

PMCID: PMC8554646 PMID: 34713449

Abstract

Background

Oncoplastic breast‐conserving surgery (O‐BCS) involves removing the tumour in the breast and using plastic surgery techniques to reconstruct the breast. The adequacy of published evidence on the safety and efficacy of O‐BCS for the treatment of breast cancer compared to other surgical options for breast cancer is still debatable. It is estimated that the local recurrence rate is similar to standard breast‐conserving surgery (S‐BCS) and also mastectomy, but the aesthetic and patient‐reported outcomes may be improved with oncoplastic techniques.

Objectives

Our primary objective was to assess oncological control outcomes following O‐BCS compared with other surgical options for women with breast cancer. Our secondary objective was to assess surgical complications, recall rates, need for further surgery to achieve adequate oncological resection, patient satisfaction through patient‐reported outcomes, and cosmetic outcomes through objective measures or clinician‐reported outcomes.

Search methods

We searched the Cochrane Breast Cancer Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via OVID), Embase (via OVID), the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov on 7 August 2020. We did not apply any language restrictions.

Selection criteria

We selected randomised controlled trials (RCTs) and non‐randomised comparative studies (cohort and case‐control studies). Studies evaluated any O‐BCS technique, including volume displacement techniques and partial breast volume replacement techniques compared to any other surgical treatment (partial resection or mastectomy) for the treatment of breast cancer.

Data collection and analysis

Four review authors performed data extraction and resolved disagreements. We used ROBINS‐I to assess the risk of bias by outcome. We performed descriptive data analysis and meta‐analysis and evaluated the quality of the evidence using GRADE criteria. The outcomes included local recurrence, breast cancer‐specific disease‐free survival, re‐excision rates, complications, recall rates, and patient‐reported outcome measures.

Main results

We included 78 non‐randomised cohort studies evaluating 178,813 women. Overall, we assessed the risk of bias per outcome as being at serious risk of bias due to confounding; where studies adjusted for confounding, we deemed these at moderate risk.

Comparison 1: oncoplastic breast‐conserving surgery (O‐BCS) versus standard‐BCS (S‐BCS)

The evidence in the review found that O‐BCS when compared to S‐BCS, may make little or no difference to local recurrence; either when measured as local recurrence‐free survival (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.61 to 1.34; 4 studies, 7600 participants; very low‐certainty evidence) or local recurrence rate (HR 1.33, 95% CI 0.96 to 1.83; 4 studies, 2433 participants; low‐certainty evidence), but the evidence is very uncertain due to most studies not controlling for confounding clinicopathological factors. O‐BCS compared to S‐BCS may make little to no difference to disease‐free survival (HR 1.06, 95% CI 0.89 to 1.26; 7 studies, 5532 participants; low‐certainty evidence). O‐BCS may reduce the rate of re‐excisions needed for oncological resection (risk ratio (RR) 0.76, 95% CI 0.69 to 0.85; 38 studies, 13,341 participants; very low‐certainty evidence), but the evidence is very uncertain. O‐BCS may increase the number of women who have at least one complication (RR 1.19, 95% CI 1.10 to 1.27; 20 studies, 118,005 participants; very low‐certainty evidence) and increase the recall to biopsy rate (RR 2.39, 95% CI 1.67 to 3.42; 6 studies, 715 participants; low‐certainty evidence). Meta‐analysis was not possible when assessing patient‐reported outcomes or cosmetic evaluation; in general, O‐BCS reported a similar or more favourable result, however, the evidence is very uncertain due to risk of bias in the measurement methods.

Comparison 2: oncoplastic breast‐conserving surgery (O‐BCS) versus mastectomy alone

O‐BCS may increase local recurrence‐free survival compared to mastectomy but the evidence is very uncertain (HR 0.55, 95% CI 0.34 to 0.91; 2 studies, 4713 participants; very low‐certainty evidence). The evidence is very uncertain about the effect of O‐BCS on disease‐free survival as there were only data from one study. O‐BCS may reduce complications compared to mastectomy, but the evidence is very uncertain due to high risk of bias mainly resulting from confounding (RR 0.75, 95% CI 0.67 to 0.83; 4 studies, 4839 participants; very low‐certainty evidence). Data on patient‐reported outcome measures came from single studies; it was not possible to meta‐analyse the data.

Comparison 3: oncoplastic breast‐conserving surgery (O‐BCS) versus mastectomy with reconstruction

O‐BCS may make little or no difference to local recurrence‐free survival (HR 1.37, 95% CI 0.72 to 2.62; 1 study, 3785 participants; very low‐certainty evidence) or disease‐free survival (HR 0.45, 95% CI 0.09 to 2.22; 1 study, 317 participants; very low‐certainty evidence) when compared to mastectomy with reconstruction, but the evidence is very uncertain. O‐BCS may reduce the complication rate compared to mastectomy with reconstruction (RR 0.49, 95% CI 0.45 to 0.54; 5 studies, 4973 participants; very low‐certainty evidence) but the evidence is very uncertain due to high risk of bias from confounding and inconsistency of results. The evidence is very uncertain for patient‐reported outcome measures and cosmetic evaluation.

Authors' conclusions

The evidence is very uncertain regarding oncological outcomes following O‐BCS compared to S‐BCS, though O‐BCS has not been shown to be inferior. O‐BCS may result in less need for a second re‐excision surgery but may result in more complications and a greater recall rate than S‐BCS. It seems that O‐BCS may give better patient satisfaction and surgeon rating for the look of the breast, but the evidence for this is of poor quality, and due to lack of numerical data, it was not possible to pool the results of different studies. It seems O‐BCS results in fewer complications compared with surgeries involving mastectomy.

Based on this review, no certain conclusions can be made to help inform policymakers. The surgical decision for what operation to proceed with should be made jointly between clinician and patient after an appropriate discussion about the risks and benefits of O‐BCS personalised to the patient, taking into account clinicopathological factors. This review highlighted the deficiency of well‐conducted studies to evaluate efficacy, safety and patient‐reported outcomes following O‐BCS.

Plain language summary

Oncoplastic breast‐conserving surgery (O‐BCS) for women with primary breast cancer

Background

Traditional surgery for early breast cancer is standard breast‐conserving surgery (S‐BCS) which aims to keep as much of the breast as possible. For women with large tumours compared to their breast size it can be difficult to conserve the breast whilst ensuring all the tumour is removed and may mean that mastectomy is needed. The most important part of surgical treatment for breast cancer is removing all cancer. In recent years, oncoplastic breast surgery techniques have been used to conserve the breast whilst removing breast cancer by applying the principles of plastic surgery, resulting in better cosmetic results. Oncoplastic breast‐conserving surgery (O‐BCS) may also result in better patient satisfaction and quality of life.

Traditionally, surgeons have either preserved the breast tissue by removing the cancerous lump (S‐BCS) or reconstructing immediately after mastectomy. O‐BCS involves removing cancer and either moving/adjusting the remaining breast tissue around (volume displacement) or bringing in tissue from elsewhere to fill the defect after breast cancer removal (volume replacement). There are many techniques that fall under O‐BCS that we have listed in full in other parts of the review; however, all are similar in their principle.

Review question

We reviewed the evidence about the effects of O‐BCS (that is, removing some of the breast tissue and then reconstructing the remaining breast by either mobilising the breast tissue (mammaplasty or volume displacement) or bringing the tissue from elsewhere (partial breast reconstruction or volume replacement)) compared to other S‐BCS (that is, removing the tumour in the breast without the need for further breast adjustment) or mastectomy (that is, removing all the breast tissue with or without reconstruction). We studied the effect on cancer‐related (local recurrence, disease‐free survival and overall survival), quality of life and cosmetic outcomes in women with breast cancer.

Study characteristics

The evidence is current to August 2020. We included 78 studies involving 178,813 patients with breast cancer. We split the studies into those that compared O‐BCS to S‐BCS, O‐BCS to mastectomy alone and O‐BCS to mastectomy with reconstruction. Some studies contributed to more than one comparison.

Key results

It seemed that O‐BCS resulted in similar rates of local recurrence (that is, whether cancer returned in the same breast) and disease‐free survival (free of any breast cancer after initial treatment) when compared to S‐BCS, and resulted in less need for a second re‐excision surgery (which may be required if the tumour is not fully removed in the first operation). O‐BCS may result in more complications and more biopsies in the years after the surgery compared to S‐BCS. It seems that O‐BCS may give better patient satisfaction and surgeon rating for the look of the breast, but the evidence for this is of poor quality, and due to lack of numerical data, it was not possible to pool the results of different studies.

It was not possible to conclude whether or not cancer outcomes of local recurrence and disease‐free survival for O‐BCS were similar to mastectomy with or without reconstruction as there were not many good‐quality studies. It seems O‐BCS has fewer complications than surgeries involving mastectomy.

In practice, the decision to select O‐BCS should be done through shared decision making with the surgeon, discussing the potential risks and benefits.

Certainty of evidence

The certainty of the evidence in this review was very low. The studies had several methodological flaws. Differences between groups in cancer stage and other cancer treatments that were used may have affected the results. This is likely to have an impact on the findings, and future research is needed to investigate the topic further.

Summary of findings

Background

Description of the condition

Breast cancer is the most commonly diagnosed cancer in women worldwide (Bray 2018). Globally, incidence rates are increasing but mortality rates are decreasing with improved treatments, leaving many more breast cancer survivors (WHO 2010). 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 primary 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 large variation across countries in the 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 volume displacement or partial 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: 1) volume displacement techniques use breast tissue (glandular or dermoglandular) from the same breast and places (redistributes) it into the surgical site (also known as mammoplasty); and 2) volume replacement techniques use tissue, other than the breast, 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.

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 adipofascial flaps (Kijima 2014; Ogawa 2007);
- thoracoepigastric flaps (Hamdi 2014; Kijima 2011; Takeda 2005);
  - superior epigastric artery perforator flap;
  - medial intercostal artery perforator;
  - internal mammary artery perforator;
  - anterior intercostal artery perforator.
Defects in the lateral half of the breast can be reconstituted with lateral chest wall perforator flaps such as:
- lateral intercostal artery perforator (Hamdi 2006; Hu 2018);
- lateral thoracic artery perforator (McCulley 2015);
- thoracodorsal artery perforator flap (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 (Raja 1997);
- omental flaps (Zaha 2014);
- other free flaps for partial breast reconstruction e.g. transverse upper gracilis 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 S‐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 BCS 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 cancer, studies have shown that there is no detectable difference in overall survival or disease‐free survival in those who have BCS plus radiotherapy and those who have a mastectomy (Poggi 2003; Van Maaren 2016). There has been 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 BCS 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

Methods

Criteria for considering studies for this review

Types of studies

We planned to include all randomised controlled trials (RCTs) assessing oncoplastic breast‐conserving surgery (O‐BCS) but anticipated that there would be no RCTs on the topic. We, therefore, expanded the inclusion criteria to include comparative non‐randomised studies (i.e. cohort studies, case‐control studies and prospectively designed patient registries).

We included studies published in all languages from 1980 onwards as this is the date at which partial breast reconstruction was introduced.

We excluded single‐arm studies, expert opinion and duplicate studies.

Types of participants

We included women with primary breast cancer who underwent any O‐BCS using either volume displacement or partial replacement breast reconstruction for cancer compared with women who underwent any other surgical technique for cancer.

We excluded 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
partial volume replacement techniques
- abdominal adipofascial flaps/advancement flaps
- lateral chest wall perforator flaps
  - lateral intercostal artery perforator flap
  - lateral thoracic artery perforator
  - thoracodorsal artery perforator flap
- latissimus dorsi mini‐flap
- thoracoepigastric flaps
  - superior epigastric artery perforator flap
  - medial intercostal artery perforator
  - internal mammary artery perforator
  - anterior intercostal artery perforator
- omental flaps
- free flaps for partial breast reconstruction

We included any other techniques if mentioned in the literature.

Comparator interventions

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

standard breast‐conserving surgery (S‐BCS) e.g. wide local excision (WLE), quadrantectomy, segmentectomy, partial mastectomy;
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 analyses were:

any O‐BCS versus S‐BCS
any O‐BCS versus mastectomy without reconstruction
any O‐BCS versus mastectomy with reconstruction procedures

Co‐interventions

We recognised that some women with breast cancer may also undergo hormonal therapy, chemotherapy or radiotherapy, or a combination of therapies. We collected data on whether patients received these co‐interventions; we did not, however, conduct a subgroup analysis as no study reported outcomes based on these. This information can be found in Table 4, which describes confounding variables; differences in these co‐interventions informed the risk of bias for each study.

1. Confounding variables.

Study name	Clinicopathological variables: significantly different	Clinicopathological variables: demonstrated balance	Clinicopathological variables: matched	Clinicopathological variables: statistical adjustment	Co‐interventions: significantly different	Co‐interventions: demonstrated balance	Co‐interventions: matched	Co‐interventions: statistical adjustment
Acea‐Nebril 2005	Size (BCS)	Age (BCS, Mx), size (Mx)	‐	‐	‐	‐	‐	‐
Acea‐Nebril 2017	Age, menopausal status, tumour size, tumour stage, axillary lymph node status, location of tumour, multifocality	BMI, histological type, immunohistochemical receptors	‐	‐	Neoadjuvant CT, axillary management	‐	‐	‐
Acosta‐Marin 2014	Preoperative bra size, tumour size,	Age, BMI	‐	‐	‐	‐	‐	‐
Amitai 2018	Age, axillary node status, immunohistochemical receptors,	Smoking status, BMI, histological type, tumour size	‐	‐	‐	Adjuvant RT	‐	‐
Angarita 2020	Age, BMI, race, smoking status, alcohol consumption, COPD, PCI, HTN, bleeding disorder, steroid use, previous vascular disease, previous cardiac surgery, dialysis,hemiplegia, TIA, CVA, ASA status, histological type	Weight loss, transfusion, diabetes mellitus	‐	‐	Axillary management, neoadjuvant chemotherapy, anaesthetic technique	‐	‐	‐
Atallah 2015		Age, BMI, menopausal status, tumour size, location, histological type, immunohistochemical receptors	‐	‐	‐	‐	‐	‐
Bali 2018	Tumour size	Age, histological type, immunohistochemical receptors, tumour locations	‐	‐	Neoadjuvant CT, adjuvant CT	Adjuvant RT	‐	‐
Borm 2019	Age, tumour size, tumour grade, axillary node status, immunohistochemical receptors (ER status),	Immunohistochemical receptors (PR, HER2)	‐	‐	Adjuvant CT, adjuvant ET	Neo‐adjuvant CT, adjuvant RT	‐	‐
Carter 2016	Age (BCS, Mx, Mx+R), BMI (BCS), tumour size (BCS, Mx, Mx+R), tumour stage (BCS, Mx, Mx+R), tumour grade (BCS), axillary node status (BCS), immunohistochemical receptors (HER2), multifocality (BCS, Mx, Mx+R).	BMI (Mx, Mx+R), Tumour grade (Mx, Mx+R), axillary node status (Mx, Mx+R), immunohistochemical receptors (ER, PR‐ Mx), lymphovascular invasion	In LR calculation multivariate analysis	‐	Neoadjuvant CT (BCS, Mx, Mx+R), adjuvant RT (Mx/MxR), adjuvant CT (BCS, Mx, Mx+R)	Adjuvant RT (BCS)	‐	‐
Cassi 2016	‐	Age, BMI, tumour size	‐	‐	‐	Adjuvant RT	‐	‐
Chakravorty 2012	Histological type, tumour size, grade, sample weight	Age, axillary node status	‐	‐	Neoadjuvant CT	Adjuvant RT, adjuvant CT	‐	‐
Chauhan 2016 (1)	Age, tumour size, tumour location	Histological type, grade, axillary node status, immunohistochemical receptors	‐	‐	‐	‐	‐	‐
Chauhan 2016 (2)	Age, tumour size, tumour location	Axillary node status	‐	‐	‐	‐	‐	‐
Crown 2015	Tumour size, immunohistochemical receptors	Age, histological type	‐	‐	‐	Adjuvant RT	‐	‐
Crown 2019	Tumour size, immunohistochemical receptors	Age, smoking, BMI, histological type	‐	‐	Neoadjuvant CT	Adjuvant CT	‐	‐
DeLorenzi 2016 (1)	Tumour size and multifocality	Menopausal, histological type, grade, axillary node status, immunohistochemical receptors, lymphovascular invasion	Age (within 5 years), year of surgery (within 2 years), tumour size (T) and multifocality			Adjuvant CT, Adjuvant RT, Adjuvant ET	‐	‐
DeLorenzi 2016 (2)	Multifocality	Grade, immunohistochemical receptors	Age (within 5 years), year of surgery (within 2 years), number of positive axillary lymph nodes, tumour subtype, multifocality		Adjuvant RT	Adjuvant CT, Adjuvant ET	‐	‐
DeLorenzi 2018	Menopausal, grade	Age, BMI, tumour size, immunohistochemical receptors, multifocality	‐	‐	‐	Adjuvant RT, any adjuvant therapy	‐	‐
Di Micco 2017	Age, axillary node status	Smoking status, BMI, histological type, tumour size, immunohistochemical receptor, tumour location			Radiation boost, adjuvant CT	Neoadjuvant CT, adjuvant ET, axillary management, adjuvant RT
Dolan 2015	Age, tumour size, axillary node status	Histological type, grade, immunohistochemical receptor	‐	‐	Adjuvant CT	Adjuvant RT, adjuvant ET, axillary management	‐	‐
Down 2013	Tumour size	Age, histological type, grade	‐	‐	‐	Adjuvant RT	‐	‐
Eichler 2013	Tumour size	Age, histological type, grade	‐	‐	Neoadjuvant CT	Adjuvant CT	‐	‐
Fan 2019	‐	Histological type	Age, BMI, stage	‐	‐	Neoadjuvant CT, adjuvant RT, adjuvant CT, adjuvant ET		‐
Farooqi 2019	Tumour size,	Age, histological type	‐	‐	‐	Neoadjuvant CT	‐	‐
Gendy 2003	Histological type, tumour size	Age, grade, axillary node status	‐	‐	Adjuvant RT	‐	‐	‐
Gicalone 2007 (1)	Age	BMI, histological type, tumour size, grade, axillary node status, immunohistochemical receptor	‐	‐	‐	‐	‐	‐
Gicalone 2007 (2)	Age	BMI, tumour size, tumour location		‐	‐	‐	‐	‐
Gicalone 2015	‐	Age, smoking status, diabetes, BMI, other medical comorbidities, histological type, tumour size		‐	‐	‐	‐	‐
Gulcelik 2013	‐	Age, tumour size, immunohistochemical receptor	‐	‐	‐	Adjuvant CT, Adjuvant ET, axillary management, adjuvant RT
Hamdi 2008	Age, histological type, tumour size,	‐	‐	‐	‐	Axillary management	‐	‐
Hart 2015	Age, BMI	Stage	‐	‐	Adjuvant RT	‐	‐	‐
Hashimoto 2019	‐	‐	‐	‐	‐	‐	‐	‐
Hilli‐Betz 2014	Tumour size, preoperative bra size	Axillary node status	‐	‐	‐	Axillary management	‐	‐
Hu 2019	‐	Age, tumour size, immunohistochemical receptor	‐	‐	‐	Neoadjuvant CT, axillary management	‐	‐
Jiang 2015	‐	Age, weight, histology type,tumour size, grade, stage, tumour location	‐	‐	‐	‐	‐	‐
Kahn 2013	‐	‐	‐	‐	‐	Adjuvant CT (BCS, Mx, Mx+R)	‐	‐
Keleman 2019	Preoperative bra size, axillary node status	Age, smoking status, diabetes, BMI, type of cancer, tumour size, grade, stage, immunohistochemical receptor	‐	‐	Neoadjuvant CT, adjuvant CT, adjuvant ET, axillary management	Adjuvant RT	‐	‐
Kelsall 2017	‐	Axillary node status	Age, tumour size, date of surgery, breast size	‐	Adjuvant RT	Neoadjuvant CT	Adjuvant CT, adjuvant ET	‐
Kimball 2018	Age, medical comorbidities, histological type	BMI	‐	‐	Adjuvant RT, adjuvant CT, axillary management		‐	‐
Klit 2017	Age (BCS, Mx), BMI (BCS, Mx), tumour size (BCS, Mx), axillary node status (BCS, Mx)	‐	‐	‐	Axillary management, Adjuvant RT (BCS)	Adjuvant CT (BCS, Mx), Adjuvant RT (Mx)	‐	‐
Lansu 2014	‐	Age, tumour size, tumour location	‐	‐	Neoadjuvant CT	Adjuvant CT, Adjuvant ET, axillary management, adjuvant RT		‐
Lee 2018	Tumour size (BCS, Mx, Mx+R), stage (BCS, Mx, Mx+R)	Age (BCS, Mx, Mx+R), BMI (BCS, Mx, Mx+R)	‐	‐	‐	‐	‐	‐
Losken 2009	Age, histological type, stage	BMI	‐	‐	Adjuvant CT, axillary surgery	Adjuvant RT	‐	‐
Losken 2014	Age, BMI	Histological type, tumour size, stage, immunohistochemical receptor	‐	‐	Neoadjuvant CT		‐	‐
Malhaire 2015	‐	‐	‐	‐	‐	‐	‐	‐
Mansell 2015	Age (both), histological type (BCS), tumour size (BCS), grade (BCS), axillary node status (BCS), immunohistochemical receptor (ER, PR)	Histological type (Mx), tumour size (Mx), grade (Mx), axillary node status (Mx), immunohistochemical receptor (HER2)	‐	‐	Adjuvant RT (MxR), adjuvant CT (BCS), adjuvant ET (BCS)	Adjuvant RT (BCS), adjuvant CT (MxR), adjuvant ET (MxR)	‐	‐
Mansell 2017	Age (both), histological type (BCS), tumour size (BCS), grade (BCS), axillary node status (BCS), immunohistochemical receptor (ER)	Histological type (Mx), tumour size (Mx), grade (Mx), axillary node status (Mx), immunohistochemical receptor (HER2)	‐	‐	Adjuvant RT (MxR), adjuvant CT (BCS), adjuvant ET (BCS)	Adjuvant RT (BCS), adjuvant CT (MxR), adjuvant ET (MxR)	‐	‐
Matrai 2014	Tumour size	Age, histological type, grade, tumour location, bra size, immunohistochemical receptor, axillary lymph node status	Matched of clinicopathological factors ‐ details not given	‐	Adjuvant CT	Axillary surgery, adjuvant RT, adjuvant ET	‐	‐
Mazouni 2013	Immunohistochemical receptor (ER), tumour location	Histological type, tumour size, grade, axillary node status, immunohistochemical receptor (PR)	‐	‐	‐	Axillary surgery, neoadjuvant CT, adjuvant RT	‐	‐
Morrow 2019	Age (all), histological type (BCS, Mx), tumour size (BCS, Mx), grade (BCS, Mx), axillary node status (Mx, MxIR)	Histological type (MxIR), tumour size (MxIR), grade (MxIR), axillary node status (BCS), immunohistochemical receptors	‐	‐	Adjuvant CT (BCS), Adjuvant RT (all)	Adjuvant CT (Mx, MxIR), adjuvant ET (Mx, MxIR)	‐	‐
Mukhtar 2018	Tumour size	"No significant difference in patient or tumour characteristics"	‐	‐	‐	‐	‐	‐
Mustonen 2004	Tumour size	Age	‐	‐	Adjuvant, RT	Adjuvant CT	‐	‐
Nakada 2019	‐	‐	‐	‐	‐	‐	‐	‐
Nakagomi 2019	Age, tumour size, stage	Histological type, axillary node status, immunohistochemical receptor status	‐	‐	Neoadjuvant CT	‐	‐	‐
Niinikoski 2019 (2)	Age, tumour size, grade, axillary node status, immunohistochemical status (ER, TN), multifocality,	Histological type, immunohistochemical receptor status (PR, HER2)	‐	‐	Adjuvant CT, adjuvant ET	Adjuvant RT, axillary management	‐	‐
Ojala 2017	Tumour size, tumour location, axillary node status, multifocality, histological type,	Age, grade	‐	‐	Axillary management	Adjuvant RT	‐	‐
Ozmen 2016	Age, BMI, multifocality	‐	‐	‐	‐	Adjuvant RT	‐	‐
Ozmen 2020	Age, menopausal status, BMI, tumour size, grade, axillary node status, immunohistochemical receptor status (ER), multifocality	histological type, immunohistochemical receptor status (PR, HER2, TN)	‐	‐	Adjuvant RT, axillary management	‐	‐	‐
Palsodittlir 2018	Age, smoking status, tumour size	Histological type, axillary node status	‐	‐	Adjuvant ET	‐	‐	‐
Peled 2014	Age, BMI	Smoking status, diabetes	‐	‐	‐	Neoadjuvant CT	‐	‐
Piper 2016	Tumour stage	BMI, histological type	Age	‐	‐	‐	‐	‐
PlaFarnos 2018	Multifocality	‐	‐	‐	Previous breast surgery	‐	‐	‐
Potter 2020	Age (Mx, Mx+R), diabetes (Mx, Mx+R), BMI (Mx, Mx+R), other medical comorbidities ( Mx, Mx+R), histological type (Mx, Mx+R), grade (Mx, Mx+R), axillary node status (Mx, Mx+R), immunohistochemical receptors (BCS, Mx, Mx+R), multifocality (BCS, Mx, Mx+R)	Smoking status (Mx, Mx+R)	‐	‐	Neoadjuvant CT (Mx, Mx+R), adjuvant RT (Mx, Mx+R), adjuvant CT (Mx, Mx+R), axillary surgery (Mx, Mx+R)	‐	‐	‐
Ren 2014	‐	Histological type, tumour location	Age, tumour size, axillary lymph node status, immunohistochemical receptor, (ER, HER2)	‐	‐	‐	‐	‐
Rose 2019	Menopausal status, axillary node status	‐	‐	Age, lymphovascular invasion, grade, tumour size, multifocality, immunohistochemical receptor (ER, HER2)	Axillary surgery	Adjuvant RT, adjuvant CT, adjuvant ET	‐	‐
Rose 2020	‐	‐	‐	Age, follow‐up time, menopausal status, tumour size, bra size, tumour location, bra size, BMI, smoking status, marital status, living arrangement and education	‐	‐	‐	Adjuvant RT, adjuvant CT, adjuvant ET, immunotherapy, axillary surgery
Santos 2015	BMI, histological type, axillary node status,	Age, menopausal status, tumour size, grade, immunohistochemical receptor, tumour location	‐	‐	‐	Axillary surgery	‐	‐
Scheter 2019	Age, smoking status, tumour size, ,	Preoperative bra size, axillary lymph node status	Diabetes, BMI	‐	‐	Axillary surgery, adjuvant CT, adjuvant ET, adjuvant RT	‐	‐
Sherwell‐Cabello 2006	Tumour size	Age, other comorbidities, axillary node status, tumour location	‐	‐	Neoadjuvant CT	‐	‐	‐
Srivastava 2018	‐	‐	Margin of excision	‐	‐	‐	‐	‐
Tang 2016		Age, BMI, tumour size, stage	‐	‐	‐	Axillary management	‐	‐
Tenofsky 2014	‐	Age, BMI, tumour size	‐	‐	Adjuvant RT	‐	‐	‐
Tong 2016	Age, diabetes, BMI, other comorbidities, preoperative bra size	Smoking status, tumour size, stage	‐	‐	Neoadjuvant RT, adjuvant RT	Neoadjuvant CT, adjuvant CT	‐	‐
Viega 2010	‐	Age, BMI, tumour location	‐	‐	‐	Adjuvant RT, adjuvant CT	‐	‐
Viega 2011	‐	Age, BMI, tumour size, tumour location	‐	‐	‐	Adjuvant RT, adjuvant CT, axillary management	‐	‐
Vieira 2016	‐	Age, histological type, stage, immunohistochemical receptor	Tumour size, grade	‐	‐	Neoadjuvant CT, adjuvant RT	‐	‐
Wijgman 2017	Tumour size, tumour location	Age, menopausal status, smoking, diabetes, BMI, other medical comorbidities, histological type, sample volume resected, sample weight resected	‐	‐	Adjuvant CT, adjuvant ET	Neoadjuvant CT, adjuvant RT, axillary surgery	‐	‐
Wong 2017	Tumour size	‐	‐	‐	‐	‐	‐	‐
Zhou 2019	Tumour size	Age, BMI, preoperative bra size, histological type, tumour location, multifocality, axillary node status	‐	‐	‐	Adjuvant RT, axillary management	‐	‐

Study	Control	Confounding	Selection	Classification of intervention	Deviations from intended intervention	Missing data	Measurement of outcomes	Selection of reported results	Overall
Acea‐Nebril 2017	S‐BCS	Serious	Low	Low	Moderate	Low	Low	Moderate	Serious
		Some clinicopathological variables significantly different (age, menopausal status, tumour size, tumour stage, axillary lymph node status, location of tumour, multifocality). Some co‐interventions balanced (neoadjuvant CT and axillary management), some missing	All participants eligible included	Classification of interventions clear and determined at the start of intervention. Some aspects maybe determined retrospectively	Deviation from intended co‐intervention (adjuvant therapy time), co‐interventions significantly different	All patients followed up	Objective outcome measure	No indication of selected reporting
Borm 2019	S‐BCS	Serious	Low	Low	Low	Moderate	Low	Moderate	Serious
		Most clinicopathological variables significantly different: age, tumour size, tumour grade, axillary node status, immunohistochemical receptors (ER status). Important co‐interventions (adjuvant CT, adjuvant ET) not balanced across intervention group and may affect the outcome	All participants eligible included	Classification of interventions clear and determined at the start of intervention. Operative details given clearly	All patients received the surgical intervention described in the methods	Analysis unlikely to have removed risk of bias from missing data	Objective outcome measure	No indication of selected reporting
DeLorenzi 2016 (1)	S‐BCS	Low	Low	Low	Low	Low	Low	Moderate	Moderate
		Important clinicopathological factors demonstrated balance (menopausal, histological type, grade, axillary node status, immunohistochemical receptors, lymphovascular invasion) or matched (age (within 5 years), year of surgery (within 2 years), tumour size. Important co‐interventions balanced across intervention group (adjuvant CT, adjuvant RT, adjuvant ET)	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	Most patients followed up	Objective outcome measure ‐ due to margin status	No indication of selected reporting
DeLorenzi 2018	S‐BCS	Moderate	Moderate	Low	Low	Low	Low	Moderate	Moderate
		Important clinicopathological factors demonstrated balance (age, BMI, tumour size, immunohistochemical receptors, multifocality), some significantly different (menopausal, grade). Some co‐interventions balanced across intervention group (adjuvant RT, any adjuvant therapy)	Selection may be related to the outcome (mastectomy eventually excluded)	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	Most patients followed up	Objective outcome measure ‐ due to margin status	No indication of selected reporting
Gulcelik 2013	S‐BCS	Moderate	Low	Low	Moderate	Low	Low	Moderate	Moderate
		Important clinicopathological factors demonstrated balance (age, tumour size, immunohistochemical receptor), most missing. Important co‐interventions demonstrated balance (adjuvant CT, adjuvant ET, axillary management, adjuvant RT)	All participants eligible included	Classification of interventions clear and determined at the start of intervention, operative details given clearly	All patients received the surgical intervention described in the methods. Included from the beginning of uptake of intervention	All patients included but some did not have sufficient follow‐up so excluded. Details not given	Objective outcome measure	No indication of selected reporting
Mansell 2017	S‐BCS	Serious	Low	Low	Low	Low	Low	Moderate	Serious
		Important clinicopathological factors significantly different: age, histological type, tumour size, grade, axillary node status, immunohistochemical receptor (ER, PR). Important co‐interventions balanced, some significantly different: adjuvant CT, adjuvant ET	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	All patients included followed up until June 2016	Objective outcome measure	No indication of selected reporting
Mazouni 2013	S‐BCS	Moderate	Low	Low	Low	Low	Low	Moderate	Moderate
		Important clinicopathological factors balance: histological type, tumour size, grade, axillary node status, immunohistochemical receptor (PR). Important co‐interventions predefined and uniform across studies (axillary surgery, neoadjuvant CT, adjuvant RT)	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	All patients included followed up	Objective outcome measure	No indication of selected reporting
Rose 2019	S‐BCS	Moderate	Low	Low	Low	Low	Low	Moderate	Moderate
		Important clinicopathological factors statistically adjusted for. Location of surgeries different in intervention and control. Some co‐interventions balanced, some missing	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in methods	Most patients included	Objective outcome measure	No indication of selected reporting
Vieira 2016	S‐BCS	Moderate	Low	Low	Low	Low	Low	Moderate	Moderate
		Important clinicopathological factors demonstrated balance. Matched for demographic and oncological aspects. Important co‐interventions demonstrated balance, missing data on axillary management of cases (97.4% for control group)	All OPS participants eligible included, matched BCS 'cases were matched to decrease a possible bias selection'	Classification of interventions clear and determined at the start of intervention: standard surgical treatment was quadrantectomy combined with level III axillary node dissection with was performed in 97.4% of patients	All patients received the surgical intervention described in methods	All patients included followed up	Objective outcome measure	No indication of selected reporting
Nakagomi 2019	Mx	Serious	Low	Low	Low	Low	Serious	Moderate	Serious
		Some variables demonstrated balance (histological type, axillary node status, immunohistochemical receptor status), some significantly different (age, tumour size, stage), many missing. Important co‐interventions missing (RT, axillary management), neoadjuvant CT significantly different	All participants eligible included	Classification of interventions clear and determined at the start of intervention: lattisimus dorsi mini flap or mastectomy	All patients received the surgical intervention described in methods	All patients included followed up	Objective outcome measure but details of follow‐up time not given	No indication of selected reporting
DeLorenzi 2016 (2)	Mx + R	Low	Low	Low	Low	Low	Low	Moderate	Moderate
		Important clinicopathological factors demonstrated balance (grade, immunohistochemical receptors) or matched (age (within 5 years), year of surgery (within 2 years), number of positive axillary lymph nodes, tumour subtype). Important co‐interventions balanced across intervention group (adjuvant CT, adjuvant ET), adjuvant RT different	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	Most patients followed up	Objective outcome measure ‐ due to margin status	No indication of selected reporting
Mansell 2017	Mx + R	Moderate	Low	Low	Low	Low	Low	Moderate	Moderate
		Some clinicopathological significantly different: age, immunohistochemical receptor (ER, PR). Other important clinicopathological factors balance: histological type, tumour size, grade, axillary node status, immunohistochemical receptor (HER2). Important co‐interventions demonstrated balance, adjuvant RT significantly different	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	All patients included followed up until June 2019	Objective outcome measure	No indication of selected reporting
Ozmen 2020	Mx + R	Serious	Moderate	Low	Moderate	Low	Low	Moderate	Serious
		Important clinicopathological factors balance, some different (age, menopausal status, BMI, tumour size, grade, axillary node status, immunohistochemical receptor status (ER), multifocality), some missing. Important co‐interventions significantly different (adjuvant RT and axillary management), some missing (neoadjuvant RT + CT, adjuvant CT + ET)	Women chose their operation after being told the potential risks and benefits. Bias in assignment: "Both two procedures were explained to patients, and their choices were recorded."	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in methods. All operations done by a single surgeon with more than 30 years of experience in breast surgery.	Most patients included: "Median follow‐up time was 56 (14‐116) months."	Objective outcome measure	No indication of selected reporting

Study	Control	Confouding	Selection	Classification of intervention	Deviations from intended intervention	Missing data	Measurement of outcomes	Selection of reported results	Overall
Acea‐Nebril 2017	S‐BCS	Serious	Low	Low	Moderate	Low	Low	Moderate	Serious
		Some clinicopathological variables significantly different (age, menopausal status, tumour size, tumour stage, axillary lymph node status, location of tumour, multifocality). Some co‐interventions balanced (neoadjuvant CT and axillary management), some missing	All participants eligible included	Classification of interventions clear and determined at the start of intervention. Some aspects maybe determined retrospectively	Deviation from intended co‐intervention (adjuvant therapy time) but does not impact this outcome	All patients followed up	Objective outcome measure (from date of surgery to date of treatment)	No indication of selected reporting
Borm 2019	S‐BCS	Serious	Low	Low	Low	Low	Low	Moderate	Serious
		Most clinicopathological variables significantly different: age, tumour size, tumour grade, axillary node status, immunohistochemical receptors (ER status). Important co‐interventions (adjuvant CT, adjuvant ET) not balanced across intervention group and may effect the outcome	All participants eligible included	Classification of interventions clear and determined at the start of intervention. Operative details given clearly	All patients received the surgical intervention described in the methods	All patients followed up	Objective outcome measure	No indication of selected reporting
Cassi 2016	S‐BCS	Serious	Low	Low	Low	Low	Low	Moderate	Serious
		Some clinicopathological variables demonstrated balance, most missing. Important co‐interventions balanced across intervention group (adjuvant RT,) some information missing	All participants eligible included	Classification of interventions clear and determined at the start of intervention. Operative details given clearly	All patients received the surgical intervention described in the methods	Most patients followed up	Objective outcome measure	No indication of selected reporting
Di Micco 2017	S‐BCS	Moderate	Serious	Low	Low	Low	Low	Moderate	Serious
		Important clinicopathological factors demonstrated balance (smoking status, BMI, histological type, tumour size, immunohistochemical receptor, tumour location), some significantly different (age, axillary node status). Some co‐interventions balanced across intervention group (neoadjuvant CT, adjuvant ET, axillary management, adjuvant RT), some different (radiation boost, adjuvant CT)	Selection may be related to the outcome (mastectomy eventually)	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	Most patients followed up	Objective outcome measure	No indication of selected reporting
Kahn 2013	S‐BCS	Serious	Low	Moderate	No information	Low	Serious	Moderate	Serious
		Clinicopathological factors missing. Adjuvant CT balanced	All participants eligible included, consecutive patients to reduce selective bias	Some plane mobilisation without skin reduction counted as WLE. This is standard practice so minor risk of bias due to this	‐	All patients included followed up	Date calculated from when MDT decided to give CT, this is not an objective date and could be different across the two groups	No indication of selected reporting
Keleman 2019	S‐BCS	Moderate	Moderate	Low	Low	Moderate	Low	Moderate	Moderate
		Some variables demonstrated balance (age, smoking status, diabetes, BMI, type of cancer, tumour size, grade, stage, immunohistochemical receptor) some different (preoperative bra size, axillary node status) but unlikely to affect outcome. Important co‐intervention of adjuvant RT demonstrated balance, some significantly different (neoadjuvant CT, adjuvant CT, adjuvant ET, axillary management) but less of an impact on outcome	All intervention participants eligible included, random patients selected for control	Classification of interventions clear and determined at the start of intervention. The types of intervention were: therapeutic mammaplasty (superior, central, inferior pedicle Wise‐pattern), Dermoglandular rotation (medial, lateral mammoplasty), Periareolar (round block, omega) or standard BSC	All patients received the surgical intervention described in the methods	Patients missed due to loss to follow‐up and did not respond to outcome, equal numbers in both groups so impact may be similar across groups	Objective outcome measure	No indication of selected reporting
Kimball 2018	S‐BCS	Serious	Moderate	Moderate	Low	Low	Moderate	Moderate	Serious
		Some clinicopathological variables demonstrated balance (BMI) and some different (age, medical comorbidities, histological type), some missing ‐ issue with the database. Important co‐interventions significantly different (adjuvant RT, adjuvant CT, axillary management)	Selection based on coding ‐ not standardised for OPS yet	Classification of intervention based on codes ‐ not uniform across sites. Types of intervention: partial mastectomy (‘lumpectomy’) and three breast reconstructive/repair procedures	All patient received the surgical intervention described in methods	All patients included followed up	From coding in insurance companies	No indication of selected reporting
Klit 2017	S‐BCS	Serious	Moderate	Low	Low	Low	Low	Moderate	Serious
		Some differences in clinicopathological characteristics (age, BMI, tumour size, axillary node status), unlikely to have major impact on outcome. Important co‐interventions significantly different (axillary management), some balanced (adjuvant CT)	Excluded patients with unclear resection margins, needs for further surgery (could influence outcome)	Classification of interventions clear and determined at the start of intervention. Surgical treatment consisted of mastectomy, lumpectomy or O‐BCS in combination with either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND)	All patients received the surgical intervention described. The surgical and adjuvant treatments were standardized according to DBCG guidelines	All patients included followed up	Objective outcome measure	No indication of selected reporting
Matrai 2014	S‐BCS	Serious	Serious	Low	Low	Low	Low	Moderate	Serious
		Tumour size significantly different. Some variables demonstrated balance (age, histological type, grade, tumour location, bra size, immunohistochemical receptor, axillary lymph node status). Matching of patients reported but not defined: "the same clinicopathological parameters of 60 traditional breast‐conserving surgeries operated by the same breast surgeon were used". Important co‐interventions including adjuvant RT demonstrated balance. Adjuvant CT significantly different	Unclear why these 60 patients selected (not consecutive, some retrospective and some prospective), controls matched	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	All patients included followed up	Objective outcome measure	No indication of selected reporting
Mazouni 2013	S‐BCS	Moderate	Low	Low	Low	Low	Serious	Moderate	Serious
		Important clinicopathological factors balance: histological type, tumour size, grade, axillary node status, immunohistochemical receptor (PR). Important co‐interventions predefined and uniform across studies (axillary surgery, neoadjuvant CT, adjuvant RT)	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	All patients included followed up	Unclear date from which time until adjuvant therapy calculated	No indication of selected reporting
Morrow 2019	S‐BCS	Serious	Low	Low	Low	Low	Low	Moderate	Serious
		Some variables demonstrated balance (histological type (MxIR), tumour size (MxIR), grade (MxIR), axillary node status, immunohistochemical receptors), some significantly different (age (all), histological type (BCS, Mx), tumour size (BCS, Mx), grade (BCS, Mx), axillary node status (Mx, MxIR)). Important co‐interventions significantly different (adjuvant RT)	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	All patients included followed up	Objective outcome measure	No indication of selected reporting
Palsodittlir 2018	S‐BCS	Serious	Moderate	Low	Low	Low	Low	Moderate	Serious
		Some variables demonstrated balance, some significantly different (e.g. tumour size), some missing (grade, stage, location of tumour). Adjuvant ET balanced, some co‐interventions missing: radiotherapy, chemotherapy, axillary management	All women included according to selection criteria. Selection criteria excluded level 2 O‐BCS procedures assigning these as minimal: "Level 1 and level 2 oncoplastic procedures (minimal gland mobilization techniques) were not included in the study group."	Classification of interventions clear and determined at the start of intervention	All patient received the surgical intervention described in methods	All patients included followed up	Objective outcome measure	No indication of selected reporting
Rose 2019	S‐BCS	Moderate	Low	Low	Low	Low	Low	Moderate	Moderate
		Important clinicopathological factors statistically adjusted for. Location of surgeries different in intervention and control. Accounted for by measuring time to adjuvant therapy in all locations. Some co‐interventions balanced (adjuvant RT, adjuvant CT, adjuvant ET), axillary surgery different	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patient received the surgical intervention described in methods	Most patients included	Objective outcome measure: time from day of surgery to first day of therapy	No indication of selected reporting
Tenofsky 2014	S‐BCS	Serious	Serious	Low	Low	Low	Low	Moderate	Serious
		Some variables demonstrated balance, some significantly different, some missing (histological type, grade, stage, axillary node status). Important co‐interventions significantly different (adjuvant RT), some missing (neoadjuvant RT + CT, adjuvant CT + ET, axillary management)	Participants were excluded if they went on to require mastectomy 6 months after procedure, or if lost to follow‐up within 6 months: "Patients were excluded if they received a mastectomy within 6 months of the lumpectomy, and/or if they received 6 months of follow‐up after their procedure."	Classification of interventions clear and determined at the start of intervention	All patient received the surgical intervention described in methods	All patients included followed up	Objective outcome measure	No indication of selected reporting
Kahn 2013	Mx	Serious	Low	Moderate	No information	Low	Serious	Moderate	Serious
		Clinicopathological factors missing. Adjuvant CT balanced	All participants eligible included, consecutive patients to reduce selective bias	Some plane mobilisation without skin reduction counted as WLE. This is standard practice so minor risk of bias due to this	‐	All patients included followed up	Date calculated from when the multi‐disciplinary team decided to give CT, this is not an objective date and could be different across the two groups	No indication of selected reporting
Klit 2017	Mx	Serious	Serious	Low	Low	Low	Low	Moderate	Serious
		Some differences in clinicopathological characteristics (age, BMI, tumour size, axillary node status), unlikely to have major impact on outcome. Important co‐interventions significantly different (axillary management), some balanced (adjuvant CT)	Excluded patients with unclear resection margins, needs for further surgery (could influence outcome)	Classification of interventions clear and determined at the start of intervention. Surgical treatment consisted of mastectomy, lumpectomy or OBS in combination with either SLNB or ALND	All patients received the surgical intervention described. The surgical and adjuvant treatments were standardised according to DBCG guidelines	All patients included followed up	Objective outcome measure	No indication of selected reporting
Morrow 2019	Mx	Serious	Low	Low	Low	Low	Low	Moderate	Serious
		Some variables demonstrated balance (histological type (MxIR), tumour size (MxIR), grade (MxIR), axillary node status (BCS), immunohistochemical receptors), some significantly different (age (all), histological type (BCS, Mx), tumour size (BCS, Mx), grade (BCS, Mx), axillary node status (Mx, MxIR)). Important co‐interventions significantly different (adjuvant RT)	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	All patients included followed up	Objective outcome measure	No indication of selected reporting
Potter 2020	Mx	Serious	Moderate	Low	Low	Low	Low	Moderate	Serious
		Important clinicopathological factors significantly different (age, diabetes, BMI, other medical co‐morbidities, histological type,grade, axillary node status, immunohistochemical receptors, multifocality). Tumour size missing. Important co‐interventions significantly different (neoadjuvant CT, adjuvant RT, adjuvant CT, axillary surgery)	Selection from participants in other studies (iBRA‐2 and TeaM studies )	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in methods	All patients included followed up	Objective outcome measure	No indication of selected reporting
Kahn 2013	Mx + R	Serious	Low	Moderate	No information	Low	Serious	Moderate	Serious
		Clinicopathological factors missing. Adjuvant CT balanced	All participants eligible included, consecutive patients to reduce selective bias	Some plane mobilisation without skin reduction counted as WLE. This is standard practice so minor risk of bias due to this	‐	All patients included followed up	Date calculated from when MDT decided to give CT, this is not an objective date and could be different across the two groups	No indication of selected reporting
Morrow 2019	Mx + R	Serious	Low	Low	Low	Low	Low	Moderate	Serious
		Some variables demonstrated balance (histological type (MxIR), tumour size (MxIR), grade (MxIR), axillary node status (BCS), immunohistochemical receptors), some significantly different (Age (all), histological type (BCS, Mx), tumour size (BCS, Mx), grade (BCS, Mx), axillary node status (Mx, MxIR)). Important co‐interventions significantly different (adjuvant RT)	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patients received the surgical intervention described in the methods	All patients included followed up	Objective outcome measure	No indication of selected reporting
Potter 2020	Mx + R	Serious	Moderate	Low	Low	Low	Low	Moderate	Serious
		Important clinicopathological factors significantly different (age, diabetes, BMI, other medical co‐morbidities, histological type,grade, axillary node status, immunohistochemical receptors, multifocality). Tumour size missing. Important co‐interventions significantly different (neoadjuvant CT, adjuvant RT, adjuvant CT, axillary surgery)	Selection from participants in other studies (iBRA‐2 and TeaM studies )	Classification of interventions clear and determined at the start of intervention	All patient received the surgical intervention described in methods	All patients included followed up	Objective outcome measure	No indication of selected reporting
Tong 2016	Mx + R	Serious	Low	Low	Low	Moderate	Moderate	Moderate	Serious
		Some variables demonstrated balance, some significantly different (age, Diabetes, BMI, other comorbidities, preoperative bra size), some missing. Important co‐interventions significantly different (neoadjuvant RT, adjuvant RT), some missing	All participants eligible included	Classification of interventions clear and determined at the start of intervention	All patient received the surgical intervention described in methods	All patients included followed up, but median follow‐up was significantly different between groups. "Median follow‐up was 4 months longer for the oncoplastic breast reconstruction group than for the immediate breast reconstruction group (18.7 months versus 14.0 months, respectively; P < 0.001)"	Objective outcome measure. Unclear why delay is defined as over 6 weeks "Complications that delayed the initiation of adjuvant chemotherapy or radiation therapy for greater than 6 weeks postoperatively were recorded." Outcome measure likely only minimally influenced by knowledge of intervention	No indication of selected reporting

Countries	Number
Belgium	1
Brazil	4
China	4
Denmark	3
Europe	2
Finland	3
France	6
Germany	3
Hungary	2
Iceland	1
India	2
Israel	2
Italy	2
Japan	3
Korea	2
Mexico	1
Netherlands	2
Pakistan	1
Spain	3
Turkey	3
UK	13
USA	14
Venezuela	1

	Intervention
Control	Volume displacement	Volume replacement	Both
BCS	39	6	13
Mx	0	3	0
Mx+R	3	2	1
Mx+‐R	0	0	1
BCS/Mx	2	0	0
BCS/Mx+‐R	0	0	2
BCS/Mx/Mx+R	2	0	2
Mx/Mx+R	1	0	0

Any O‐BCS compared to S‐BCS for women with primary breast cancer
Patient or population: women with primary breast cancer Setting: mixed multicentre/single‐centre studies with initial inpatient procedure and outpatient follow‐up  Intervention: any O‐BCS Comparison: S‐BCS
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with S‐BCS	Risk with any O‐BCS
Local recurrence‐free survival (up to 5 years)	Study population		HR 0.90 (0.61 to 1.34)	7600 (4 observational studies)	⊕⊝⊝⊝ Very low^a,b	We calculated estimates of risk with BCS using an average of non‐adjusted baseline control rates from included studies.
	55 per 1000	50 per 1000 (34 to 73)
Local recurrence rates (up to 5 years)	Study population		HR 1.33 (0.96 to 1.83)	2443 (4 observational studies)	⊕⊕⊝⊝ Low^b,c	We calculated estimates of risk with BCS using an average of non‐adjusted baseline control rates from included studies.
	57 per 1000	75 per 1000 (55 to 102)
Disease‐free survival (up to 5 years)	Study population		HR 1.06 (0.89 to 1.26)	5532 (7 observational studies)	⊕⊕⊝⊝ Low^b,c	We calculated estimates of risk with BCS using an average of non‐adjusted baseline control rates from included studies.
	98 per 1000	104 per 1000 (88 to 122)
Re‐excision rate: total re‐excisions	Study population		RR 0.76 (0.69 to 0.85)	13,341 (38 observational studies)	⊕⊝⊝⊝ Very low^a,d,e	We also assessed the risk of completion mastectomy (RR 1.00, 95% CI 0.85 to 1.15); O‐BCS may have no effect on the completion mastectomy rate but the evidence is very uncertain.
	134 per 1000	101 per 1000 (92 to 114)
Complications	Study population		RR 1.19 (1.10 to 1.27)	118,005 (20 observational studies)	⊕⊝⊝⊝ Very low^a,b,f	O‐BCS may increase or have no effect on the rate of complications but the evidence is very uncertain.
	34 per 1000	41 per 1000 (38 to 44)
Recall rate	Study population		RR 2.39 (1.67 to 3.42)	715 (6 observational studies)	⊕⊕⊝⊝ Low^a	O‐BCS may increase recall rate slightly.
	100 per 1000	240 per 1000 (167 to 343)
Patient‐reported outcome measures	There is no significant difference in quality of life patient‐reported outcome measures using BREAST‐Q. However, there may be better patient‐reported cosmetic satisfaction with O‐BCS		‐	5665 (24 observational studies)	⊕⊝⊝⊝ Very low^a,g	The evidence is very uncertain about the effect of any O‐BCS on patient‐reported outcome measures.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; HR: hazard ratio; O‐BCS: oncoplastic breast‐conserving surgery; RR: risk ratio; S‐BCS: standard breast‐conserving surgery.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Any O‐BCS compared to mastectomy for women with primary breast cancer
Patient or population: women with primary breast cancer Setting: mixed multicentre/single‐centre studies with initial inpatient procedure and outpatient follow‐up Intervention: any O‐BCS Comparison: mastectomy
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with Mx	Risk with any O‐BCS
Local recurrence‐free survival (up to 5 years)	Study population		HR 0.55 (0.34 to 0.91)	4713 (2 observational studies)	⊕⊝⊝⊝ Very low^a,b	Estimates of risk with BCS were calculated using an average of non‐adjusted baseline control rates from included studies.
	161 per 1000	92 per 1000 (58 to 148)
Cumulative local recurrence rate				(0 studies)	‐	No studies evaluated local recurrence as cumulative rate
Disease‐free survival	Study population		RR 0.58 (0.41 to 0.82)	1193 (1 observational study)	⊕⊝⊝⊝ Very low^c,d	Dichotomous data used as no studies reported time‐to‐event data
	139 per 1000	81 per 1000 (57 to 114)
Re‐excision rates				(0 studies)		Re‐excisions are not often needed for mastectomy, therefore this outcome is not relevant for this comparison.
Complications	Study population		RR 0.75 (0.67 to 0.83)	4839 (4 observational studies)	⊕⊝⊝⊝ Very low^c,e	O‐BCS may reduce complications compared to mastectomy but the evidence is very uncertain.
	312 per 1000	234 per 1000 (209 to 259)
Recall rates				(0 studies)		Recall biopsies are not often needed for mastectomy, therefore this outcome is not relevant for this comparison.
Patient‐reported outcome measures	There are insufficient data to make any conclusions		‐	(1 observational study)	‐	There are insufficient data to make any conclusions
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BCS: breast‐conserving surgery; CI: confidence interval; HR: hazard ratio;Mx: mastectomy; O‐BCS: oncoplastic breast‐conserving surgery; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Any O‐BCS compared to mastectomy plus reconstruction for women with primary breast cancer
Patient or population: women with primary breast cancer Setting: mixed multicentre/single‐centre studies with initial inpatient procedure and outpatient follow‐up Intervention: any O‐BCS Comparison: mastectomy plus reconstruction (Mx+R)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with Mx+R	Risk with any O‐BCS
Local recurrence‐free survival	Study population		HR 1.37 (0.72 to 2.62)	3785 (1 observational study)	⊕⊝⊝⊝ Very low^a,b	Any O‐BCS may result in little to no difference in local recurrence‐free survival compared to Mx+R. Estimates of risk with BCS were calculated using an average of non‐adjusted baseline control rates from included studies. Also calculated HR for LRR (local recurrence rates) for studies with a comparison of Mx+/‐R where the vast majority were reconstructed; HR 1.59 (0.71 to 3.55)
	43 per 1000	58 per 1000 (31 to 108)
Cumulative local recurrence rate				0 studies		Re‐excisions are not often needed for mastectomy, therefore this outcome is not relevant for this comparison and therefore not studied.
Disease‐free survival	Study population		HR 0.45 (0.09 to 2.22)	317 (1 observational study)	⊕⊝⊝⊝ Very low^a,c	Estimates of risk with BCS were calculated using an average of non‐adjusted baseline control rates from included studies. Also calculated HR for DFS for studies with a comparison of Mx+/‐R where the vast majority were reconstructed; HR 1.03 (0.75 to 1.42)
	189 per 1000	90 per 1000 (19 to 371)
Re‐excision rates				0 studies	‐	Re‐excisions are not often needed for mastectomy, therefore this outcome is not relevant for this comparison.
Complications	Study population		RR 0.49 (0.45 to 0.54)	4973 (5 observational studies)	⊕⊝⊝⊝ Very low^a,d
	492 per 1000	241 per 1000 (221 to 266)
Recall rates				0 studies	‐	Recall biopsy is not often needed for mastectomy, therefore this outcome is not relevant for this comparison.
Patient‐reported outcome measures	The evidence is too methodologically diverse and of high risk of bias due to measurement of outcomes to combine		‐	(3 observational studies)	‐	There is insufficient evidence to make a conclusion
The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BCS: breast‐conserving surgery; CI: confidence interval; DFS: disease‐free survival; HR:* hazard ratio;Mx: mastectomy; Mx+R: mastectomy with reconstruction; Mx+/‐R: mastectomy with or without reconstruction; O‐BCS: oncoplastic breast‐conserving surgery; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Study	Wound infection	Flap necrosis	Dehisence	Fat necrosis	Seroma	Skin	Haematoma	Bleeding	Needed surgery
Acea‐Nebril 2017‐VD	1 (0.5%)	4 (2.3%)	‐	‐	3 (1.7%)	‐	4 (2.3%)	3 (1.7%)	(1.7%) ‐ bleeding only
Acea‐Nebril 2005‐VD	2 (4%)	3 (6%)	‐	‐	3 (6%)	‐	4 (8%)	‐	‐
Acosta‐Marin 2014‐VD	1 (1.9%)	‐	‐	1 (1.9%)	‐	1 (1.9%)	‐	‐	‐
Amitai 2018‐VD	‐	‐	‐	15 (22%)	‐	‐	‐	‐	‐
Angarita 2020‐VD	209 (2.3%)	‐	67 (0.7%)	‐	‐	‐	‐	22 (0.3%)	‐
Carter 2016‐VD	45 (4.8%)	‐	‐	‐	126 (13.4%)	‐	18 (1.9%)	‐	‐
Chauhan 2016 (1)‐VD and VR	4 (7%)	2 (3.5%)	‐	‐	1 (1.8%)	‐	1 (1.8%)	‐	‐
Chauhan 2016 (2)‐VD and VR	1 (3.67%)	1 (3.7%)	‐	‐	0 (0%)	‐	1 (3.7%)	‐	‐
Jiang 2015‐VD	‐	‐	1 (3.3%)	‐	3 (10%)	‐	‐	‐	‐
Tang 2016‐VD and VR	0 (0%)	0 (0%)	2 (3%)	0 (0%)	10 (15%)	10 (15%)	3 (4.48%)	0 (0%)	‐
Crown 2019‐VD	15 (3.3%)	‐	14 (3.1%)	‐	8 (1.8%)	2 (0.4%)	‐	‐	‐
DeLorenzi 2016 (1)‐Both	13 (2.8%)	6 (1.3%)	16 (3.5%)	12 (2.6%)	‐	‐	11 (2.4%)	‐	‐
Dolan 2015‐VD and VR	‐	‐	‐	‐	‐	‐	‐	‐	5 (7%)
Down 2013‐VD and VR	2 (5.4%)	‐	‐	‐	‐	‐	‐	‐	breakdown only
Gicalone 2007 (1)‐VD	‐	21 (67%)	5 (16%)	‐	‐	‐	2 (6.45%)	‐	‐
Gicalone 2007 (2)‐VD	‐	‐	2 (5.13%)	‐	‐	1 (2.6%)	1 (2.6%)	‐	‐
Gicalone 2015‐VD	4 (9.52%)	‐	‐	‐	‐	2 (4.8%)	1 (2.4%)	‐	‐
Keleman 2019‐VD	8 (2.3%)	3 (0.9%)	‐	2 (0.57%)	5 (1.4%)	‐	2 (0.6%)	‐	‐
Kimball 2018‐VD	17.7 (2.5%)	33.3 (4.7%)	‐	‐	‐	‐	6.4% (includes seroma)	‐	< 1%
Mazouni 2013 ‐ VD	‐	‐	‐	‐	‐	‐	‐	‐	4 (2%)
Nakada 2019‐VR	‐	68 (16%)	‐	‐	‐	‐	‐	‐	‐
Palsodittlir 2018‐VD and VR	‐	0 (0%)	‐	‐	‐	‐	0 (0%)	‐	‐
Scheter 2019‐VD	‐	‐	2 (16.7%)	1 (8.3%)	‐	‐	‐	‐	0
Tenofsky 2014‐VD	5 (8.6%)	‐	4 (6.9%)	15 (25.9%)	10 (17.2%)	21 (36.2%)	10 (17.2%)	‐	‐
Wijgman 2017‐VD	11 (4%)	‐	‐	‐	17 (6.2%)	‐	31 (11.4%)	‐	6 (1.9%)
Zhou 2019‐VR	‐	‐	‐	‐	3 (9.3%)	‐	0 (0%)	‐	3 (9.3%)

Study	Wound infection	Flap/skin necrosis	Dehisence	Fat necrosis	Seroma	Skin	Haematoma	Bleeding	Needed surgery
Acea‐Nebril 2017‐ BCS	13 (2%)	1 (0.1%)	‐	‐	21 (3.3%)	‐	22 (3.3%)	‐
Acea‐Nebril 2005‐ BCS	2 (3.5%)	0	‐	‐	8 (13.9%)	‐	5 (8.7%)	‐	‐
Acosta‐Marin 2014‐ BCS	0	‐	‐	0	‐	0	‐	‐	‐
Amitai 2018‐ BCS	‐	‐	‐	3 (1%)	‐	‐	‐	22	‐
Angarita 2020‐ BCS	1842 (1.8%)	‐	126 (0.1%)	‐	‐	‐	‐	‐	‐
Carter 2016‐ BCS	32 (1.4%)	‐	‐	‐	406 (18%)	‐	57 (2.5%)	‐	‐
Chauhan 2016 (1)‐ BCS	2 (3.5%)	‐	‐	‐	1 (1.8%)	‐	1 (1.75%)	‐	‐
Chauhan 2016 (2) ‐ BCS	2 (4.3%)	1 (2.2%)	‐	‐	2 (4.3%)	‐	‐	‐	‐
Jiang 2015‐ BCS	‐	‐	4 (13.3%)	‐	2 (6.7%)	‐	‐	0 (0%)	‐
Tang 2016‐ BCS	3 (2.6%)	0 (0%)	16 (13.7%)	2 (1.71%)	57 (48.7%)	21 (17.9%)	17 (14.5%)	0 (0%)	‐
Crown 2019‐ BCS	21 (8.4%) P = 0.01	‐	13 (4.7%)	‐	12 (4.4%)	2 (0.7%)	‐	‐	‐
DeLorenzi 2016 (1)‐ BCS	‐	‐	‐	‐	‐	‐	‐	‐	3 (2.6%)
Dolan 2015‐ BCS	‐	‐	‐	‐	‐	‐	‐	‐
Down 2013‐ BCS	3 (2.5%)	‐	‐	1 (0.8%)	‐	‐	‐	‐	‐
Gicalone 2007 (1)‐ BCS	‐	‐	1 (2.3%)	‐	‐	‐	3 (6.7%)	‐	‐
Gicalone 2007 (2)‐ BCS	‐	‐	3 (3.4%)	‐	‐	0 (0%)	1 (1.14%)	‐	‐
Gicalone 2015‐ BCS	5 (8.8%)	‐	‐	‐	‐	0 (0%)	2 (3.5%)	‐	‐
Keleman 2019‐ BCS	7 (2%)	2 (0.6%)	‐	1 (0.3%)	9 (2.6%)	‐	4 (1.1%)	‐	<1%
Kimball 2018‐ BCS	298 (1.7%)	702 (4%)	‐	‐	‐	‐	1000 (5.7%)	‐	‐
Nakada 2019‐ BCS	‐	‐	‐	‐	‐	‐	‐	‐	2 (1%)
Palsodittlir 2018‐ BCS	‐	26 (4.6%)	‐	‐	‐	‐	‐	‐	1 (0.2%)
Scheter 2019‐ BCS	‐	5 (0.8%)	‐	‐	‐	‐	11 (1.67%)	‐	16 (2.4$%)
Tenofsky 2014‐ BCS	‐	‐	1 (8.3%)	0 (0%)	‐	‐	‐	‐	0 (0%)
Wijgman 2017‐ BCS	8 (9.5%)	0	4 (4.8%)	8 (9.5)%)	15 (17.2%)	21 (25%)	8 (9.5%)	‐	‐
Zhou 2019‐ BCS	12 (2.6%)	‐	‐	‐	23 (5%)	‐	59 (12.8%)	‐	1 (0.2%)

	Intervention details	Intervention results	S‐BCS results
Amitai 2018	VD	7/12 due to lump needed more imaging	7/14 due to a lump needed more imaging
Dolan 2015	Both VD and VR	Imaging per patient: 2.19 ultrasound: 20/71 VD: 16/61 VR: 4/10	Imaging per patient: 2.146, ultrasound 17/119
Fan 2019	VR	3.2%	1%
Hu 2019	VR	1/18 1.4%	0
Losken 2009	VD	Further US, MRI imaging: 41.0%	Further US, MRI imaging: 47.0%, 6.0%

Intervention details	Time to any adjuvant therapy: intervention	Time to any adjuvant therapy: control	P value	Time to adjuvant chemotherapy: intervention	Time to adjuvant chemotherapy: control	P value	Time to adjuvant radiotherapy: intervention	Time to adjuvant radiotherapy: control	P value
Di Micco 2017‐ VD	‐	‐	‐	Median (range) 39 (21 to 78)	40 (11 to 81)	0.551	Median (range) 57 (36 to 153)	53 (25 to 126)	0.025
Keleman 2019‐ VD	Median (range) 29.4 (28 to 84)	28.7 (28 to 84)	0.31	‐	‐	‐	‐	‐	‐
Kimball 2018‐ VD	‐	‐	‐	Median (IQR) 37 (23.5 to 51.5)	36 (26 to 49)	0.0004	Median (IQR) 41 (28 to 56)	34 (22 to 48)	0.0002
Morrow 2019‐ VD	‐	‐	‐	Less than 31 days: 14.9%	Less than 31 days: 22.1%	0.171	Median (range) 51 (35 to 125)	50 (10 to 447)	0.088
Palsodittlir 2018‐ VD and VR	Median (range) 47.5 (22 to 111)	50 (15 to 202)	0.05	‐	‐	‐	‐	‐	‐

Study: intervention details	Outcome measure	Intervention: quality of life	Intervention: cosmetic	Intervention: other	Control: quality of life	Control: cosmetic	Control: other	P value	Conclusion
Keleman 2019 ‐ VD	EORTC	Median (range) emotional functioning score: 91.6 (50‐100), social functioning score: 83.4 (33‐100)	Median (range): body image score: 91.6 (50‐100)	‐	Emotional functioning score: 83.4 (50‐100), Social functioning score: 75.0 (50‐100)	Body image score was 75.0 (33‐100)	‐	< 0.01/< 0.01/< 0.01	OPS significantly better in emotional/social/body image
Lansu 2014 ‐ VD	EORTC QLQ C30 and BR23 and Young Boost Trial	C30 function scale: 75.9 (22.57) C30 symptom scale: 17.31 (10.2) C30 QOL: 63.45(35.77) BR23 fuction scale: 70.19(16.30) BR23 symptom scale: 20.51 (12.35)	YBT 26.94 (15.03)	‐	C30 function scale: 92.34 (5.89) C30 symptom scale: 14.51 (11.18) C30 QOL: 87.96(7.30) BR23 function scale: 84.17(7.3) BR23 symptom scale: 11.9 (8.32)	YBT 31.35 (23.79)	‐	0.28/0.57/0.05/0.06/0.07/0.93	BCS significantly better in C30 QOL but otherwise no SD
Matrai 2014 ‐ VD	Q 47‐53 of Hungarian EORTC and self‐designed cosmetic	The quality of life questions, "Did you feel any arm or shoulder pain?" (P = 0.0399), "Did you have difficulty raising or moving your arm to the side?" (P = 0.0060) and “Did you feel any pain in the affected chest area?” (P = 0.0304) showed a significant advantage in the OPS group.	8.73 (1.023) 61.7% had 9/10 or 10/10	‐	‐	7.35 (1.5) ‐ 23.3% had 9/10 or 10/10	‐	< 0.001	Significantly better PR cosmetic score in OPS than control. Significantly less shoulder disability and chest pain in OPS group.
Acosta‐Marin 2014 ‐ VD	Self‐designed	‐	Mean: 4.4 ‐ 88.4% (4/5 (good) or 5/5 (excellent))	‐	‐	Mean: 4.2 83.4% (4/5 (good) or 5/5 (excellent))	‐	0.644	No SD
Jiang 2015 ‐ VD	Self‐designed	‐	28 (93.3%) satisfied	‐	‐	25 (83.3%) satisfied	‐	‐	More satisfied in OPS
Tang 2016 ‐ VD and VR	Self‐designed	‐	62/67 satisfied	‐	‐	92/117 satisfied	‐	0.025	Significantly more satisfied in OPS
Eichler 2013 ‐ VD	Self‐designed	Overall satisfaction (4‐5/5): 86%	Satisfied with overall appearance: 83%	‐	Overall satisfaction (4‐5/1‐5): 87%	Satisfied with overall appearance: 87%	No significant difference in overall, shape, appearance, size, quality of life, sensitivity in nipple, swelling, self‐confidence. Significant better satisfaction with appearance/amount of scar tissue in BCS compared to OPS	Overall satisfaction: 0.48 Cosmetic evaluation: 0.91 Scar satisfaction: 0.013	No SD in most domains. Scar satisfaction better in BCS
Gicalone 2007 (2) ‐ VD	Self‐designed	‐	32/39 (4‐5/5)		‐	63/88 (4‐5/5)	‐	0.23	No SD of cosmetic satisfaction between patient groups
Hilli‐Betz 2014 ‐ VD	Self‐designed	‐	92.8% ‐ very satisfied with the cosmetic appearance of their breasts. No difference in physical attractiveness	More PROMS in paper	‐	83.5% ‐ very satisfied with the cosmetic. No difference in physical attractiveness	More PROMS in paper	0.189/0.435	No SD in PROMs in paper
Mazouni 2013 ‐ VD	Self‐designed	‐	Moderately satisfied: 12.5%; satisfied: 37.5%; very satisfied: 50%	‐	‐	Moderately satisfied: 14.5%, satisfied: 47.9%, very satisfied: 37.6%	‐	0.52	No SD in cosmetic difference
Palsodittlir 2018 ‐ VD and VR	Self‐designed	‐	97% happy with aesthetic outcome of surgery	‐	‐	89% happy	‐	‐	Greater proportion of patients in OPS happy with the aesthetic outcome
Santos 2015 ‐ VD	Self‐designed	‐	35 excellent (61.4%)	‐	‐	45 excellent (69.2%)	‐	0.242	No SD in patient‐reported cosmetic score
Sherwell‐Cabello 2006 ‐ VD	Self‐designed	Overall QOL 4.77	4.81	‐	4.81	4.72	‐	0.256	No SD in any parameters. High levels of aesthetic acceptance and mild psychological and social impact on patients.
Tenofsky 2014 ‐ VD	Self‐designed	‐	8 complained of unfavourable cosmetic outcomes (13.8%)	‐	‐	6 (7.1%) complained of unfavourable cosmetic outcome	‐	0.191	No SD in patient‐reported complaints of cosmetic outcome
Viega 2011 ‐ VD	Self‐designed	‐	10 (9‐10)/10	‐	‐	10 (5‐10)/10	‐	< 0.001	OPS is better than standard BCS
Zhou 2019 ‐ VR	Self‐designed and DASH	‐	28 (87.5) extremely satisfied	DASH 10.57	‐	22 (78.6) extremely satisfied	DASH 7.86	NS/0.06	No SD in overall outcome or DASH questionnaires scores

Study	Intervention details	Assesment details	Intervention results	Control results	P‐value	Conclusion
Acosta‐Marin 2014	VD	Self‐designed, 4 person panel (1 plastic surgeon, 1 breast surgeon, 2 surgical oncologists)	Mean 4.5/5	4.1/5	< 0.005	O‐BCS better than control (S‐BCS)
Jiang 2015	VD	Self‐designed ‐ grade 1‐3 (1 best, 1 and 2 satisfactory) by 1 doctor, 1 nurse, 1 non‐professional	93.3% satisfactory	83.3% satisfactory	‐	O‐BCS better than control (S‐BCS)
Gicalone 2007 (2)	VD	Self‐designed, panel (1 surgeon, 1 oncologist)	33; 4‐5/5	11; 4‐5/5	0.006	O‐BCS (Donught mastopexy) significantly better cosmetic results than standard lumpectomy (S‐BCS)
Hilli‐Betz 2014	VD	Self‐designed, 1 surgeon evaluation	Excellent in 8.7%, good in 63.8%, moderate in 24.6%, and poor in 0.0%	Excellent in 32.2%, good in 60.9%, moderate in 5.6%, and poor in 0.6%	0.191	O‐BCS (Dermoglandular rotation) significantly worse than standard segmentectomy
Keleman 2019	VD	Self‐designed ‐ 3 surgeons panel	Median (range) 4.4 (3‐5)/5	Median (range) 3.2 (1‐5)/5	0.001	O‐BCS significantly better than control
Santos 2015	VD	2 plastic surgeon panel	Excellent in 50.9%, good in 40.4%, moderate in 7%, and poor in 1.8%	Excellent in 18.5%, good in 61.5%, moderate in 18.5%, and poor in 1.5%	< 0.001	O‐BCS significantly better than control
Scheter 2019	VD	Self‐designed, 13 plastic surgeon panel (1‐10) 10 excellent	Shape: 7.9; Symmetry: 7.9 Volume: 8.1	Shape: 5.5 Symmetry: 5.4 Volume: 6.2	0.002/0.016/0.012	O‐BCS significantly better than control
Viega 2011	VD and VR	Self‐designed ‐ 2 breast surgeons, 2 plastic surgeons (male and female of each): FBS/MBS/FPS/MPS	10/9/9/9	9/8/6/6	< 0.001/0.005/< 0.001/< 0.001	O‐BCS significantly better than control

Study	Intervention details	Time to adjuvant chemotherapy ‐ intervention	Time to adjuvant chemotherapy ‐ control	P value	Time to adjuvant radiotherapy ‐ intervention	Time to adjuvant radiotherapy ‐ control	P value
Morrow 2019	VD	Less than 31 days: 14.9%	Mx: 16.2% MX+R: 10.8%	0.787/0.386	Median (range) 51 (35‐125)	Mx alone: 55 (26‐428) Mx+R: 56 (33‐122)	0.626/0.747

Study	Intervention type	Wound infection	Flap/skin necrosis	Dehisence	Fat necrosis	Seroma	Skin	Haematoma	Needed surgery
Acea‐Nebril 2005	VD	2 (4%)	3 (6%)	‐	‐	3 (6%)	‐	4 (8%)	‐
Carter 2016	VD and VR	45 (4.8%)	‐	‐	‐	126 (13.4%)	‐	18 (1.9%)	‐
Mustonen 2004	VR	1 (8.3%)	1 (8.3%)	‐	‐	3 (25%)	‐	‐	‐
Ozmen 2020	VR	‐	‐	‐	‐	‐	3 (5.6%)	‐	5 (2%)
Peled 2014	VD	6 (16.2%)	‐	4 (10.8%)	‐	‐	‐	‐	1 (2.7%)
Potter 2020	VD	‐	‐	‐	‐	‐	‐	‐	8 (2.13%)
Tong 2016	VD	11 (8.4%)	0 (0%)	8 (6.1%)	5 (3.8%)	‐	18 (13.7%)	4 (3.1%)	3 (2.3%)

Study	Control Details	Wound infection	Flap/skin necrosis	Dehiscence	Fat necrosis	Seroma	Skin	Haematoma	Needed surgery
Acea‐Nebril 2005	Mx	3 (5.6%)	0 (0%)	‐	‐	14 (26.4%)	‐	2 (3.6%)	‐
Carter 2016	Mx	133 (5.8%)	‐	‐	‐	305 (13.2%)	‐	66 (2.9%)	‐
Carter 2016	Mx+R	212 (11.6%)	‐	‐	‐	228 (12.5%)	‐	87 (4.8%)	‐
Mustonen 2004	Mx+R	1 (8.3%)	1 (8.3%)	‐	‐	3 (5.6%)	‐	‐	1 (8.3%)
Ozmen 2020	Mx+R	‐	‐	‐	‐	‐	‐	‐	5 (6.7%)
Peled 2014	Mx+R	23 (35.9%)	‐	19 (29.7%)	‐	‐	‐	‐	24 (37.5%)
Potter 2020	Mx+R	‐	‐	‐	‐	‐	‐	‐	96 (9.5%)
Tong 2016	Mx+R	31 (11.2%)	41 (14.8%)	14 (5.1%)	11 (4%)	32 (11.6%) includes haematoma	14 (5.1%)	‐	27.1%

Patient‐reported outcomes (BREAST‐Q)
Study	Intervention details (type ‐ n)	Intervention BREAST‐Q (n/100)	Control	Statistics	Conclusion
Acea‐Nebril 2017	VD ‐ 60	> 80 in all domains	‐	‐	No comparison
Di Micco 2017	VD ‐170	Median: psychological = 83; satisfaction with breast = 82 evolution = 73, sexual = 70	‐	‐	No comparison
PlaFarnos 2018	VD ‐ 70	Median (IQR): satisfaction with breast: 80 (0‐100); psychosocial well‐being: 76 (0‐100); sexual well being: 46 (26‐100); physical wellbeing: 81 (37‐100)	Median (IQR): satisfaction with breast: 68 (IQR 29‐100); psychosocial well‐being: 82 (0‐100); sexual well‐being: 57 (0‐100); physical well‐being: 75 (17‐100) P = 0.32/0.71/0.08/0.422	P value: 0.32/0.705/0.079/0.422	No significant difference (SD) in any domain
Rose 2020	Both ‐ 96	No. of patients above median score psychosocial: 2.15 (1.25‐3.69); physical: 0.83 (0.5‐1.39); satisfaction with breast: 0.95 (0.57‐1.59); sexual well‐being 1.42 (0.78‐2.58)	No. of patients above median score: psychosocial: 2.15 (1.25‐3.69); physical: 0.83 (0.5‐1.39); satisfaction with breast 0.95 (0.57‐1.59); sexual well‐being; 1.42 (0.78‐2.58)	Odds ratio psychosocial: 2.15 (1.25‐3.69); physical: 0.83 (0.5‐1.39); satisfaction with breast 0.95 (0.57‐1.59); sexual well‐being: 1.42 (0.78‐2.58)	Better psychosocial well‐being in O‐BCS. No SD in any other domain
Scheter 2019	VD ‐ 12	Mean score per domains: satisfaction with breast: 75.18; psychosocial well‐being: 76.09; sexual well‐being: 78	Satisfaction with breast: 39.64; psychosocial well‐being: 43.18; sexual well‐being: 41	0.001/0.025/0.021	O‐BCS better in satisfaction of breast, psychosocial wellbeing and sexual well‐being

#	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

#	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

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Local recurrence‐free survival (time to recurrence)	8		Hazard Ratio (IV, Fixed, 95% CI)	Subtotals only
1.1.1 Local recurrence‐free survival	4		Hazard Ratio (IV, Fixed, 95% CI)	0.90 [0.61, 1.34]
1.1.2 Local Recurrence Rates	4		Hazard Ratio (IV, Fixed, 95% CI)	1.33 [0.96, 1.83]
1.2 Local recurrence	24		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
1.2.1 1 year	3	637	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.25, 2.10]
1.2.2 1 to 5 years	15	9014	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.66, 1.04]
1.2.3 5 years	10	6672	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.82, 1.39]
1.3 Disease‐free survival (HR)	7		Hazard Ratio (IV, Fixed, 95% CI)	1.06 [0.89, 1.26]
1.4 Disease‐free survival (RR)	9		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
1.4.1 1 to 5 years	3	946	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.74, 1.34]
1.4.2 5 years	6	5054	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [0.99, 1.44]
1.4.3 10 years	2	2163	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.04, 1.40]
1.5 Overall survival (HR)	8		Hazard Ratio (IV, Fixed, 95% CI)	1.02 [0.82, 1.28]
1.6 Overall survival (RR)	13		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
1.6.1 1 to 5 years	3	4970	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.60, 1.09]
1.6.2 5 years	12	8730	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.65, 0.96]
1.7 Re‐excision rates	38		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
1.7.1 Total re‐excisions	38	13341	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.69, 0.85]
1.7.2 Mastectomies	23	10756	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.85, 1.18]
1.8 Complications	20	118005	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [1.10, 1.27]
1.9 Recall rates	6	715	Risk Ratio (M‐H, Fixed, 95% CI)	2.39 [1.67, 3.42]
1.10 Time to therapy	7		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.10.1 Any adjuvant therapy	1	120	Mean Difference (IV, Fixed, 95% CI)	2.60 [‐5.48, 10.68]
1.10.2 Chemotherapy	4	4566	Mean Difference (IV, Fixed, 95% CI)	‐1.13 [‐2.55, 0.29]
1.10.3 Radiotherapy	5	3720	Mean Difference (IV, Fixed, 95% CI)	9.67 [7.21, 12.14]
1.11 Patient‐reported outcomes (BREAST‐Q)	5		Other data	No numeric data
1.12 Aesthetic outcome BCCT.core	3		Other data	No numeric data

Aesthetic outcome BCCT.core
Study	Intervention type	BCCT.core‐ Intervention	BCCT.core‐ Control	P value	Conclusion
Hilli‐Betz 2014	VD	Excellent: 4.3%, good: 75.4%, moderate: 18.8%	BCCT.core Excellent: 10.6%, good: 77.0%,  moderate in 5.6%, poor in 0.6%	< 0.001	OPS significantly worse in expert panel cosmetic than standard segnentectomy
Lansu 2014	VD	Mean (SD) 2.45 (0.52)	Mean (SD) 2.11 (0.6)	0.02	OPS significantly better than control
Santos 2015	VD	BCCT.core: Excellent: 22.8%, good: 54.4%, moderate: 21.1%, bad:1.8%, poor in 1.8%	BCCT.core Excellent: 6.2%, good: 73.8%, moderate: 15.4%, poor: 4.6%	0.004	OPS significantly better than control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Local recurrence (HR)	2		Hazard Ratio (IV, Fixed, 95% CI)	Subtotals only
2.1.1 Local recurrence‐free survival	2		Hazard Ratio (IV, Fixed, 95% CI)	0.55 [0.34, 0.91]
2.2 Local recurrence (RR)	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
2.2.1 1 to 5 years	2	4025	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.24, 0.41]
2.2.2 5 years	2	942	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.41, 1.75]
2.2.3 10 years	1	1193	Risk Ratio (M‐H, Fixed, 95% CI)	6.52 [1.42, 30.06]
2.3 Disease‐free survival	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
2.3.1 10 years	1	1193	Risk Ratio (M‐H, Fixed, 95% CI)	0.58 [0.41, 0.82]
2.4 Overall survival (HR)	2		Hazard Ratio (IV, Fixed, 95% CI)	0.39 [0.30, 0.51]
2.5 Overall survival (RR)	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
2.5.1 1 to 5 years	1	3924	Risk Ratio (M‐H, Fixed, 95% CI)	0.30 [0.22, 0.40]
2.5.2 5 years	2	932	Risk Ratio (M‐H, Fixed, 95% CI)	1.71 [0.79, 3.69]
2.6 Complications	4	4839	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.67, 0.83]
2.7 Time to therapy	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
2.7.1 Chemotherapy	1	974	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐2.23, 2.03]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Local recurrence‐free survival	3		Hazard Ratio (IV, Fixed, 95% CI)	Subtotals only
3.1.1 Local recurrence rate: Mx+/‐R	2		Hazard Ratio (IV, Fixed, 95% CI)	1.59 [0.71, 3.55]
3.1.2 Local recurrence‐free survival: Mx+R only	1		Hazard Ratio (IV, Fixed, 95% CI)	1.37 [0.72, 2.62]
3.2 Local recurrence	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.2.1 1 to 5 years	2	3449	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [0.87, 1.64]
3.2.2 5 years: Mx+R only	2	830	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.19, 1.44]
3.2.3 5 years: Mx+/‐R	2	1001	Risk Ratio (M‐H, Fixed, 95% CI)	1.54 [0.74, 3.21]
3.3 Disease‐free survival (HR): Mx+R	3		Hazard Ratio (IV, Fixed, 95% CI)	Subtotals only
3.3.1 Mx+/‐R	2		Hazard Ratio (IV, Fixed, 95% CI)	1.03 [0.75, 1.42]
3.3.2 Mx+R only	1		Hazard Ratio (IV, Fixed, 95% CI)	0.45 [0.09, 2.22]
3.4 Disease‐free survival (RR): Mx+R	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.4.1 5 years: Mx+R only	1	317	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.27, 2.04]
3.4.2 5 years: Mx+/‐R	2	1001	Risk Ratio (M‐H, Fixed, 95% CI)	0.88 [0.66, 1.18]
3.5 Overall survival (HR): Mx+R	4		Hazard Ratio (IV, Fixed, 95% CI)	Subtotals only
3.5.1 Mx+R only	2		Hazard Ratio (IV, Fixed, 95% CI)	1.74 [1.23, 2.47]
3.5.2 Mx+/‐R	2		Hazard Ratio (IV, Fixed, 95% CI)	0.65 [0.40, 1.07]
3.6 Overall survival (RR): Mx+R	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.6.1 1 to 5 years	1	3387	Risk Ratio (M‐H, Fixed, 95% CI)	1.39 [0.97, 1.98]
3.6.2 5 years: Mx only	2	830	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.24, 2.28]
3.6.3 5 years: Mx+/‐R	2	1001	Risk Ratio (M‐H, Fixed, 95% CI)	0.52 [0.33, 0.84]
3.7 Complications: Mx+R only	5	4973	Risk Ratio (M‐H, Fixed, 95% CI)	0.49 [0.45, 0.54]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Local recurrence	14		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
4.1.1 1 to 5 years	8	2578	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.51, 1.39]
4.1.2 5 years	8	4729	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.63, 1.27]
4.2 Overall survival	7		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
4.2.1 5 years	7	4373	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.59, 0.98]
4.3 Re‐excision rates	27		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
4.3.1 Total re‐excisions	27	9076	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.69, 0.87]
4.3.2 Mastectomies	16	7097	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.86, 1.28]
4.4 Complications	14	4083	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.90, 1.18]

PERMALINK

Oncoplastic breast‐conserving surgery for women with primary breast cancer

Akriti Nanda

Jesse Hu

Sarah Hodgkinson

Sanah Ali

Richard Rainsbury

Pankaj G Roy

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Experimental interventions

Comparator interventions

Co‐interventions

1. Confounding variables.

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Bibliographic searching

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Non‐randomised studies

Pre‐intervention bias

At‐intervention bias

Post‐intervention bias

2. Risk of bias for local recurrence.

3. Risk of bias for disease‐free survival.

4. Risk of bias for overall survival.

5. Risk of bias for re‐excision rates.

6. Risk of bias for complications.

7. Risk of bias for recall rates.

8. Risk of bias for time to adjuvant therapy.

9. Risk of bias for cosmetic evaluation.

10. Risk of bias for patient‐reported outcome measures.

Confounding and adjustment

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

1.

Included studies

Design

Setting

11. Countries of studies.

Population

Intervention

Comparison

12. Matrix of interventions and controls.

Primary outcomes

*Study characteristics*
Methods	Prospective single‐centre cohort March 2003 to Dec 2004 Complejo Hospitalario Universitario Juan Canalejo. La Coruña. España 160 participants
Participants	Inclusion: women with invasive/in situ breast cancer with tumours less than 3 cm in diameter (T1‐2) OR treated with neoadjuvant chemotherapy and reduced to a size less than 3 cm, axillary clinical stages N0‐N1a‐b Exclusion: women with breast cancer with T3‐4 tumours, impossibility of postoperative radiotherapy (previous radiotherapy, scleroderma, collagen diseases, pregnant women etc.), small breast size, impossibility of disease‐free margins or lack of compression technique by the patient or demand for a commitment to result.
Interventions	Intervention: volume displacement ‐ vertical/lower pedicle/single limb vertical/horizontal/rotational/lateral mammoplasty, (n = 50) Control: 1) standard BCS, (n = 57); 2) mastectomy, (n = 53)
Outcomes	Primary outcomes: No outcomes of interest Secondary outcomes: Re‐excisions Complications Other outcomes: Operative Time Length of Stay
Notes	No disclosures/funding declared

*Study characteristics*
Methods	Retrospective single centre cohort Jan 2000 to June 2016 Complejo Hospitalario Universitario a Coruña, Spain 801 participants
Participants	Inclusion: women with invasive breast carcinoma/ductal carcinoma in situ (DCIS) undergoing breast conserving surgery Exclusion: patients who underwent mastectomy as the primary intervention, patients that did not give their consent to participate in the study
Interventions	Intervention: volume displacement ‐ reduction mammoplasty, (n = 170) Control: BCS ‐ wide local excision, (n = 631)
Outcomes	Primary outcomes (median 84 +/‐ 55.6 months): Local recurrence Disease‐free survival Overall survival Secondary outcomes: Re‐exicisions Complications PROMs (Breast‐Q) Time to adjuvant therapy Other outcomes: Operative time
Notes	Some overlap with Acea‐Nebril 2005 in patient group but different controls No funding/disclosures declared

*Study characteristics*
Methods	Prospective single‐centre cohort Jan 2011 to Oct 2012 Breast Surgery Department, Centro Clinico de Estereotaxia—CECLINES, Caracas, Venezuela 107 participants
Participants	Inclusion: women with early breast cancer undergoing either standard BCS or level II OPS and with 12‐month follow‐up Exclusion: Patients who had mastectomy Patient who had a previous breast surgery due to breast cancer Patients with insufficient information/did not reach at least 12 months of follow‐up
Interventions	Intervention: volume displacement ‐ round block (40.3%), inverted‐T (26.8%), vertical scar (15.3%), raquet (7.6%), horizontal (5.7%), lower inner‐quadrant mammoplasty (3.8%), (n = 52) Control: standard BCS, (n = 55)
Outcomes	Primary outcomes: No outcomes of interest Secondary outcomes: Complications PROMs (Self‐designed) Cosmetic assessment (4‐person panel)
Notes	No disclosures/funding declared

*Study characteristics*
Methods	Retrospective single=centre cohort 2009 to 2014 Tel Aviv University, Israel 335 participants
Participants	Inclusion: women with breast cancer undergoing either immediate OPS and those undergoing lumpectomy in the same week (the first 4 lumpectomies after an OPS that week) Exclusion: simple local tissue rearrangement. Women undergoing mastectomy eventually for positive lumpectomy margins
Interventions	Intervention: volume displacement ‐ breast reduction (64%), mastopexy (30%) augmentation (6%), (n = 67) Control: BCS: lumpectomy, (n = 268)
Outcomes	Primary outcomes: Local recurrence Secondary outcomes: Re‐excisions Recall rates Complications Other outcomes: Follow‐up imaging findings
Notes	No disclosures/funding disclosed Authors were contacted requesting full dataset for primary outcomes

*Study characteristics*
Methods	Retrospective database review cohort 2005 to 2016 American College of Surgeons National Surgical Quality Improvement Program, USA 109,487 participants
Participants	Inclusion: adult women with an International Classification of Diseases Ninth Revision (ICD‐9) code of in situ (ICD‐9 code 233.0) or invasive breast cancer (ICD‐9 code 174.0–9) who underwent a traditional lumpectomy or OPS (soft tissue transfer, mastopexy, or mammoplasty) Exclusion: male patients, metastatic tumours, and concurrent surgery (non‐breast and bilateral procedures)
Interventions	Intervention: both VD and VR ‐ adjacent tissue transfer < 10 cm (4.7%), 10 cm² to 30 cm² (16.2%), 30 cm² to60 cm² (34.9%), mastopexy (23.7%), reduction (20.5%), (n = 9126) Control: BCS: lumpectomy, (n = 100,361)
Outcomes	Primary outcomes: No outcomes of interest Secondary outcomes: Complications Other outcomes: Operative time Length of Stay
Notes	No disclosures/funding declared

*Study characteristics*
Methods	Retrospective single‐centre cohort study Hotel‐Diey de France, Beirut, France 2005‐2013 280 participants
Participants	Inclusion: women with early breast cancer who underwent breast conserving surgery
Interventions	Intervention: volume displacement ‐ OPS stage 1 and 2, (n = 193) Control: wide local excision, (n = 87)
Outcomes	Primary outcomes: Local recurrence (no follow‐up time therefore excluded from analysis) Secondary outcomes: Re‐excisions Other outcomes: Margins
Notes	Conference abstract No disclosures/funding declared

*Study characteristics*
Methods	Retrospective single‐centre and surgeon cohort Apr 2014 to Sep 2016 University of Cambridge, England, UK 201 participants
Participants	Inclusion: women with breast cancer operated on by a single oncoplastic breast surgeon Exclusion: patients undergoing mastectomy
Interventions	Intervention: volume displacement and volume replacement (analysed separately) ‐ mammoplasty (19), chest wall perforator flaps (16), (n = 35) Control: BCS: wide local excision, (n = 166)
Outcomes	Primary outcomes: No outcomes of interest Secondary outcomes: Re‐excisions Other outcomes: Margins Length of stay
Notes	No disclosures/funding declared

*Study characteristics*
Methods	Retrospective single‐centre cohort January 2000 to December 2005 Klinikum rechts der Isar, Munich, Germany 965 participants
Participants	Inclusion: women with breast cancer undergoing BCS with no distant metastases at the time of diagnosis Exclusion: patients with other malignancies in addition to breast cancer
Interventions	Intervention: volume displacement ‐ rotation flap (265), reduction mammoplasty (23). 1 patient received a volume replacement flap (thoracoepigastric flap), (n = 288) Control: Standard BCS, (n = 677)
Outcomes	Primary outcomes (median 67 months (IQR 6 = 51‐84)): Local recurrence Disease free survival Overall survival Secondary outcomes: Time to adjuvant therapy Other outcomes: Distant and regional recurrence
Notes	No disclosures/funding declared

*Study characteristics*
Methods	Prospective single centre January 2012 to December 2014 Command Hospital, Lucknow (tertiary care teaching hospital), India 100 participants
Participants	Inclusion: women with locally advanced breast cancer (including stage III A, stage III B and stage IIB) and receiving doxorubicin based neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant radiotherapy Exclusion: patients with extensive peau d orange, extensive skin involvement( infiltration or ulceration), chest wall involvement or metastatic disease
Interventions	Intervention: volume displacement and replacement (analysed together) ‐ VD: periareolar, superior and inferior pedicle techniques, quadrantectomy with glandular remodeling, and dermoglandular flaps, VR: (mini LD myofascial or myocutaneous flap) (n = 57) Control: BCS: lumpectomy or quadrantectomy, (n = 43)
Outcomes	Primary outcomes: Local recurrence (Median: (I) 18 months (range 6‐30) (C) 34 months (14‐44)) Secondary outcomes: Re‐excisions Complications Other outcomes: Margins
Notes	No disclosures/funding declared Differs from Chauhan (2) in participant selection Authors were contacted requesting full dataset for primary outcomes

*Study characteristics*
Methods	Prospective single‐centre cohort January 2012 to December 2014 Tertiary teaching hospital, India 79 participants
Participants	Inclusion: women with early breast cancer (T1/T2, N0/N1) undergoing breast conserving surgery Exclusion: patients unwilling for BCS patients of locally advanced breast cancers who had undergone neoadjuvant chemotherapy patients unwilling to follow‐up at this centre patients who had undergone conventional BCS previously at outside centre and whose medical records were incomplete patients with extensive peau d'orange or extensive skin involvement (infiltration or ulceration) or chest wall involvement/multicentric disease
Interventions	Intervention: volume displacement and replacement (analysed together) ‐ lateral mammaplasty (9), medial mammaplasty (4), radial excision (5), grissotis flap (2) superior ped (5) inferior pedicl (4) donut (3) Mini LD (1), (n = 33) Control: BCS: margin or a formal quadrantectomy, (n = 46)
Outcomes	Primaryoutcomes: Local recurrence (median: (I) 18 months (range 6‐30) (C) 38 months (12‐64)) Secondaryoutcomes: Re‐excisions Complications Otheroutcomes: Margins
Notes	No disclosures/funding declared Differs from Chauhan (1) in participant selection Authors were contacted requesting full dataset for primary outcomes