Review

Knowledge gaps in oncoplastic breast surgery

Walter P Weber, Monica Morrow, Jana de Boniface, Andrea Pusic, Giacomo Montagna, Elisabeth A Kappos, Mathilde Ritter, Martin Haug,
Christian Kurzeder, Ramon Saccilotto, Alexandra Schulz, John Benson, Florian Fitzal, Zoltan Matrai, Jane Shaw, Marie-Jeanne Vrancken Peeters,
Shelley Potter, Joerg Heil, on behalf of the Oncoplastic Breast Consortium*

The aims of the Oncoplastic Breast Consortium initiative were to identify important knowledge gaps in the field of Lancet Oncol 2020; 21: e375–85
oncoplastic breast-conserving surgery and nipple-sparing or skin-sparing mastectomy with immediate breast *Contributing members of the
reconstruction, and to recommend appropriate research strategies to address these gaps. A total of 212 surgeons Oncoplastic Breast Consortium
can be found in the appendix
and 26 patient advocates from 55 countries prioritised the 15 most important knowledge gaps from a list of 38 in
Breast Center (W P Weber MD,
two electronic Delphi rounds. An interdisciplinary panel of the Oncoplastic Breast Consortium consisting of
G Montagna MD, E A Kappos MD,
63 stakeholders from 20 countries obtained consensus during an in-person meeting to select seven of these M Ritter MD, M Haug MD,
15 knowledge gaps as research priorities. Three key recommendations emerged from the meeting. First, the effect C Kurzeder MD), Department of
of oncoplastic breast-conserving surgery on quality of life and the optimal type and timing of reconstruction after Clinical Research
(R Saccilotto MD, A Schulz MSc),
nipple-sparing or skin-sparing mastectomy with planned radiotherapy should be addressed by prospective cohort
Department of Surgery
studies at an international level. Second, the role of adjunctive mesh and the positioning of implants during (W P Weber, E A Kappos, M Ritter,
implant-based breast reconstruction should ideally be investigated by randomised controlled trials of pragmatic M Haug), and Department of
design. Finally, the BREAST-Q questionnaire is a suitable tool to assess primary outcomes in these studies, but Gynecology and Obstetrics
(G Montagna, C Kurzeder),
other metrics to measure patient-reported outcomes should be systematically evaluated and quality indicators of
University Hospital Basel and
surgical morbidity should be further assessed. University of Basel, Basel,
Switzerland; Patient Advocacy
Introduction of Senology convened a consensus conference on Group, Oncoplastic Breast
Consortium, Basel, Switzerland
The emphasis on aesthetic outcomes and quality of life Feb 23, 2017, that reported substantial heterogeneity in (J Shaw BA); Breast Surgery
(QOL) after breast cancer treatment motivated surgeons several aspects of clinical oncoplastic breast-conserving Service, Memorial Sloan
to develop oncoplastic breast surgery, which includes surgery practice.10 The global Oncoplastic Breast Kettering Cancer Center,
onco­ plastic breast-conserving surgery, nipple-sparing Consortium (OPBC) has identified major disagreement New York, NY,
USA (M Morrow MD,
mastec­ tomy with immediate reconstruction, and skin- among experts concerning many questions that are G Montagna); Department of
sparing mastectomy with imme­diate reconstruction. The pertinent to nipple-sparing mastec­tomy with immediate Surgery, Capio Saint Göran's
first oncoplastic breast surgery techniques were intro­ recon­struction.11 Hospital, Stockholm, Sweden
duced into clinical practice more than 25 years ago.1–3 The aims of the consensus process described in this (J de Boniface MD); Department
of Molecular Medicine and
Nevertheless, current evidence evaluating the overall Review were to identify the most important knowledge Surgery, Karolinska Institutet,
benefits of oncoplastic breast surgery is based mainly on gaps in the field of oncoplastic breast surgery by inte­ Stockholm, Sweden
single-centre observational studies with small sample grating diverse sources of clinical evidence (including (J de Boniface); Division of
sizes and short follow-up. Applicability and generalisability personal experience drawn from contemporary practice) Plastic and Reconstructive
Surgery, Department of
of study findings in the field of oncoplastic breast- and to propose scientifically robust, but practical, Surgery, Brigham and Women’s
conserving surgery are further limited by the scarcity of strategies to address these gaps. Hospital, Boston, MA, USA
robust study designs and the complex issue of stan­
dardisation of these tailored surgical techniques (figure 1).4
Although nipple-sparing mastectomy and skin-sparing A B C
mastectomy, in conjunction with a wide range of options
for immediate reconstruction, are considered more
standard procedures than advanced oncoplastic appro­
aches, many open questions remain when applying these
techniques in clinical practice.5 Large, single-centre
studies with extended follow-ups, prospective multicentre
studies, and randomised controlled trials (RCTs) on
oncoplastic breast surgery have only been published as D E
recently as in the past 5 years.6–8
In the past few years, several organisations have
systematically evaluated and specified areas for improve­
ment in surgical breast cancer research and treatment.
The Association of Breast Surgery Gap Analysis Working
Group described various key gaps in research, including Figure 1: Typical oncoplastic breast-conserving surgery procedure
the need to assess the effectiveness of oncoplastic and (A) The procedure at a glance. (B) A photograph of the patient before surgery with preoperative marking of
the tumour in the left breast, and landmarks with the new position of the nipple on both breasts.
reconstructive surgery.9 The analysis identified several (C) A photograph of the left oncoplastic reduction mammoplasty with supra-areolar en bloc tumourectomy.
ongoing controversies that need to be resolved in this (D) A photograph of the right reduction mammoplasty, which was done for symmetry. (E) A photograph of the
clinical field. The Swiss, German, and Austrian Societies patient 3 years after surgery.

www.thelancet.com/oncology Vol 21 August 2020 e375

 Review

(Prof A Pusic MD); Cambridge Methods previously identified knowledge gaps; feedback of results
Breast Unit, Addenbrooke’s List of knowledge gaps was anonymised. Importance was defined as a need for
Hospital Cambridge,
Cambridge, UK (J Benson MD);
The identification of knowledge gaps was done according knowledge to guide clinical practice and research, as
School of Medicine, Anglia to a prespecified protocol (appendix pp 2–8). All opposed to knowledge of theoretical or purely scientific
Ruskin University, Cambridge, knowledge gaps included were identified by the presence interest.
UK (J Benson); Department of of considerable disagree­ ment (≥25%) among experts A personalised access link for the electronic question­
Surgery and Breast Health
Center, Comprehensive Cancer
during the first international consensus conference on naire for the first round was sent out on April 24, 2019, to
Center, Medical University oncoplastic breast-conserving surgery10 on Feb 23, 2017, all members of the OPBC according to the prespecified
Vienna, Vienna, Austria and the first OPBC consensus con­ference on nipple- timeline. Soon thereafter, several recipients raised con­
(F Fitzal MD); Department of sparing mastec­tomy on March 15, 2018.11 Seven expert cerns about the comprehensibility of the question­naire
Breast and Sarcoma Surgery,
National Institute of Oncology,
representatives, selected from the OPBC panel because for the patient advocates. Therefore, additional non-
Budapest, Hungary of their expertise in breast cancer management and expert explanations for all questions and a glossary,
(Z Matrai MD); Department of diversity in terms of background and nationality, were prepared by two expert representatives (WPW and JH)
Surgery, Netherlands Cancer tasked with adding key knowledge gaps in the practice and the patient advocate, JS, who has 30 years of
Institute, Amsterdam,
Netherlands
and research of oncoplastic breast surgery to this list on experience in health-care communication, were sent to
(Prof M-J Vrancken Peeters MD); the basis of their expert opinion. All 424 members of the all patient advocates on April 26, 2019.
Centre for Surgical Research, OPBC (390 surgeons and 34 patient advocates) were Participating members were asked to rank the
Bristol Medical School, Bristol,
informed of the upcoming Delphi process via a news­ importance of every knowledge gap on a 9-point Likert
UK (S Potter PhD); Bristol Breast
Care Centre, North Bristol letter and were able to give feedback and report scale from 1 (not important) to 9 (extremely important)
National Health Service Trust, additional knowledge gaps. and to recommend ten of the gaps as priorities for OPBC
Bristol, UK (S Potter); research (appendix pp 9–10). A time frame of 2·5 weeks
and Department of Obstetrics
Participants was permitted for submission of the questionnaire, with
and Gynecology, University
Breast Unit, University Given the complexity of identifying knowledge gaps in two reminders sent during that time.
Women’s Hospital Heidelberg, clinical practice and research in the field of oncoplastic All participants from the first round received a second
Heidelberg, Germany surgery, we planned to recruit a heterogeneous group of personalised access link to the electronic questionnaire
(J Heil MD)
specialised surgeons and patient advocates for the process for the second round. Participants who had not responded
Correspondence to: before the start of the study. First, we prespecified the to the first round by the stipulated deadline were
Dr Walter P Weber, Breast Center,
University Hospital Basel, Basel
inclusion of a minimum number of 85 OPBC surgeons considered to have declined to participate in the study
4031, Switzerland who had diversity in terms of background, career stage, and were not contacted again for the second round
[email protected] gender, and geography, and represented clinicians who (appendix p 7). The second questionnaire consisted of the
See Online for appendix do oncoplastic surgery in daily practice. The OPBC same list of knowledge gaps, with aggregated feedback
reflects a heterogeneous consortium of specialists and from round one. Feedback included the proportion of
patient advocates. One group of OPBC members consists participants recommending the topic for inclusion in the
of national coordinators and panellists who have perma­ OPBC research agenda and the median Likert ranking of
nent roles within the OPBC. These individuals were each item of round one, shown separately for medical
invited to join the OPBC on the basis of their expertise in professionals, patient advocates, and all participants
breast cancer management and if they had a daily clinical (appendix p 11). Participants were asked to complete the
practice primarily dedicated to breast diseases.11 A second questionnaire again to review, rerate, and reprioritise the
group of OPBC members consists of breast surgeons knowledge gaps as a result of the feedback and their own
from various backgrounds with different levels of answers to the first round. A period of 2 weeks was
experience who decided to join the OPBC by self- permitted to complete round two, with two reminders
For more on the OPBC see registration on the OPBC website. being sent.
https://oncoplasticbc.org/ Second, we planned to recruit a minimum of 15 OPBC To take account of the preferences of all participating
patient advocates from different countries. The OPBC medical professionals and patient advocates, results from
patient advocacy group consists of patients who under­ round one for those participants who did not take part in
went breast cancer surgery with or without partial or round two were used in the final analysis. The proportion
whole breast reconstruction and volunteered to support of recommendations for inclusion in the OPBC research
the mission of the OPBC. agenda and the median Likert rating of each knowledge
A questionnaire was sent to all OPBC members during gap were calculated separately for medical professionals
the Delphi process to evaluate their background and patient advocates. The mean of the proportion of
characteristics. recommendations and Likert ratings for the two groups
were used for ranking of the knowledge gaps. Ranking
Delphi process was determined first by the descending proportion of
The prioritisation of knowledge gaps was done according recommendations and, second, by the descending Likert
to a prespecified Delphi process (figure 2; appendix rating. The top 15 ranked knowledge gaps were selected
pp 3–4). Two rounds of electronic surveys were sent to all to be discussed at the OPBC consensus conference as
OPBC members to assess the importance of these potential research priorities.

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 Review

Delphi survey Selection of knowledge gaps List of knowledge gaps

preparation Knowledge gaps identified by: presence of disagreement (≥25%) among experts during two previous consensus adjusted and finalised
conferences in 2017 and 2018; expert opinion of seven expert representatives; specific literature search (PubMed by expert
and ClinicalTrials.gov); and feedback (incorporated until April 24, 2019) from OPBC members after distribution of representatives
preselected list on April 5, 2019, via newsletter (opening rate 61%)

Round One Electronic round one questionnaire with list of 38 knowledge gaps sent out on April 24, 2019, Knowledge gaps prioritised by
to all 390 surgeons and 34 patient advocates of the OPBC May 18, 2019

Participating members asked to rank importance of every knowledge gap (Likert scale 1–9)
and recommend a maximum of ten as OPBC research priorities

Concerns about the comprehensibility of the questionnaire raised by three patient advocates Results analysed by Delphi facilitator and
interpreted by expert representatives

Explanation for every single question and separate glossary prepared by an experienced Information sent to all 390 surgeons
patient advocate and expert representatives and 34 patient advocates by
newsletter on June 14, 2019, (opening
rate 60%), with comments on the
response rates of Delphi round one and
Questionnaire sent again to all patient advocates with explanations and glossary on announcement of round two
April 26, 2019

First reminder on April 29, 2019, to OPBC surgeons and patient advocates

Second reminder on May 6, 2019, to OPBC surgeons, and on May 13, 2019, to patient advocates

Round Two Electronic round two questionnaire with list of 38 knowledge gaps aggregated with feedback Knowledge gaps prioritised by
from round one sent out on June 17, 2019, to all 212 OPBC surgeons and 26 patient advocates July 14, 2019
who responded in round one

Participants asked to complete the questionnaire again to review, rerate, and reprioritise the Feedback from round one was used
knowledge gaps in light of the feedback and their own answers to the first round displayed for from those who completed round one
each knowledge gap but did not complete round two

Information sent to all 390 surgeons

and 34 patient advocates by newsletter
(opening rate 61%), with comments on
First reminder on July 1, 2019, to OPBC surgeons and patient advocates the response rates of Delphi round one
and round two and announcement
of consensus conference

Second reminder on July 8, 2019, to OPBC surgeons and patient advocates

Selection of the top 15 ranked knowledge gaps and detailed voting results sent to the OPBC panel

Top 15 ranked knowledge gaps discussed at the OPBC consensus conference on Sept 12, 2019, as potential research priorities

Figure 2: The Delphi process

The results have not yet been communicated to the entire OPBC. OPBC=Oncoplastic Breast Consortium.

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 Review

Consensus conference
Recommendation Likert scale
rate* (%) mean rating† The panel of the consensus conference on Sept 12, 2019,
consisted of 63 special guests, OPBC panellists, and
What is the optimal type of reconstruction in the setting of planned 60·9% 7·00
adjuvant radiotherapy? OPBC patient advocates from 20 countries (appendix
What is the optimal timing of reconstruction in the setting of 57·1% 7·00 pp 12–15). Special guests were selected on the basis of
planned adjuvant radiotherapy? their expertise in medical oncology, radiation oncology,
What is the effect of OPS on local recurrence risk? 48·9% 7·50 clinical epidemiology, or biostatistics, with representation
What is the effect of modern radiotherapy on local recurrence risk 47·8% 7·50 from research support units and breast surgical trainees.
after OPS, in general, and the role of partial irradiation and Breast surgical trainees responded to an adver­tise­ment
radiotherapy boost, when larger margins are achieved, in particular?
for trainees in an OPBC newsletter.
What are the indications for the use of synthetic mesh versus 47·8% 7·00 Before the conference, the 15 top-rated knowledge
biological mesh versus no mesh in IBBR?
gaps identified during the Delphi process were sent to
What are the indications for the use of prepectoral versus subpectoral 47·7% 7·50
IBBR? the panel with detailed voting results (exact recom­
What is the effect of OPS on quality of life? 42·8% 7·50 mendation rate and mean Likert score). The panel met
What is the clinical relevance of breast implant-associated anaplastic 35·2% 7·00 face to face to agree on the list of research priorities and
large cell lymphoma? to discuss the most appropriate study designs. Because
What are the best tools to measure the effect of OPS on quality of life 34·3% 7·00 many of the knowledge gaps were broad topics in the
and to allow the comparison of trial results? field of oncoplastic breast-conserving surgery and
What are the indications for the use of one-stage versus two-stage 32·8% 6·75 nipple-sparing mastectomy, or skin-sparing mastectomy,
IBBR?‡
with immediate reconstruction, more focused research
What are contraindications for nipple preservation? 32·4% 7·00 questions were developed in the patient problem,
What are the most accurate quality indicators in OPS? 29·8% 7·00 intervention, comparison, and outcome (PICO) format.12
What are the best localisation techniques for non-palpable tumours 28·1% 6·50 This specification allowed for the evalu­ation of research
in OPS?
tools and clinical trial designs to most appropriately
What are the indications for contralateral prophylactic 26·9% 7·00
mastectomy?‡§
address knowledge gaps. The degree of appropriateness
What are the advantages of OPS compared with conventional breast 24·3% 7·00
of the study design was assessed according to the
conserving surgery?¶ methodological quality, feasibility, and the expected
What are the indications for risk-reducing surgery? 23·3% 7·00 applicability of results to the respective knowledge gaps.
Is NSM or SSM safe when used for locally advanced breast cancer 22·2% 6·00 The expert representatives prepared a concise strategy
without the use of neoadjuvant chemotherapy?|| proposal that incorporated both the research question
What is the impact of surgical technology on the risk of skin flap 19·8% 6·00 and trial design to address the 15 most important
necrosis (scalpel and scissors vs electrocautery vs PlasmaBlade)? knowledge gaps. The proposal was sent to the panellists
What are contraindications for skin preservation? 19·5% 7·00 in advance and served as a basis for discussion during
What is the role of surgical axillary staging in risk-reducing NSM and 18·9% 6·00 the meeting (appendix pp 16–33).
SSM?||
After two lectures on the selection and prioritisation of
How can we coordinate training efforts in OPS?** 18·3% 7·00
knowledge gaps, voting on the top 15 gaps identified
What is the best technique for the assessment of intraoperative skin 17·4% 5·50
flap viability to reduce the risk of skin flap necrosis (eg, indocyanine
during the Delphi process took place to determine which
green fluorescence or thermography)? of these gaps should become OPBC research priorities
What is the optimal site of incision in specific situations (eg, for a 16·9% 6·00 (appendix p 34). Voting was in the format: yes, no, or
tumour <1 cm from the nipple or for an upper-inner quadrant tumour abstain. A simple majority was defined by agreement
in a large breast)? among 51–75% of the panellists and a consensus by
What is the optimal follow-up interval and imaging modality for 15·9% 7·00 agreement among more than 75% of panellists. In the
patients after NSM?
case of a consensus to add a knowledge gap to the agenda,
Does the immediate use of a compression bra or a compression 15·8% 5·50
dressing reduce the risk of skin flap necrosis?
the proposed strategy to address this gap was discussed
What is the optimal treatment of a positive retroareolar margin? 15·0% 7·00
and adjusted live on screen according to the comments of
How can we optimise current OPS classification systems for use in 14·7% 7·00
the panel. This deliberation was followed by a vote on the
clinical research? strategy (appendix p 35). In the case of a simple majority
What is the role of robotic surgery for NSM? 14·6% 4·75 voting on the knowledge gap or respective scientific
What is the best treatment of non-infectious skin breakdown after 13·8% 6·50 strategy, discussion and revoting was encouraged.
IBBR?
What are the best OPS classification systems for use in clinical practice 13·6% 6·50 Findings
by professionals and insurance companies? A total of 38 knowledge gaps were identified in the field
Should follow-up after risk-reducing NSM or SSM be tailored to the 13·0% 6·00 of oncoplastic surgery (table 1). During the first round
individual according to the amount of residual breast tissue on
imaging?
of the Delphi process, knowledge gaps were prioritised
(Table 1 continues on next page)
via the questionnaire by 212 (54%) of 390 OPBC
surgeons and 26 (76%) of 34 OPBC patient advocates
from 55 countries (appendix pp 40–50) . These values

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 Review

were higher than the minimum number of Delphi

Recommendation Likert scale
participants prespecified by the protocol. During the rate* (%) mean rating†
second round of the Delphi process, knowledge gaps
(Continued from previous page)
were reprioritised by 170 (80%) of 212 OPBC surgeons
What is the optimal timing for contralateral symmetrising 12·1% 7·00
and 20 (77%) of 26 patient advocates. As prespecified in procedures?
the protocol, feedback from round one was used from
What is the role of MRI before NSM? 11·9% 7·00
the 42 (20%) of 212 OPBC surgeons and six (23%) of
What is the optimal follow-up interval and imaging modality for 11·0% 6·75
26 patient advocates who completed round one but did patients after SSM?
not complete round two. What is the best treatment for implant-related cellulitis? 10·5% 6·00
One question (What are the advantages of oncoplasti What are the indications for retroareolar frozen section? 8·6% 6·00
breast-conserving surgery compared with conventional What is the best technique for tissue conditioning to reduce the risk 6·6% 5·50
breast-conserving surgery?) was not ranked among the of skin flap necrosis (eg, nitroglycerine, or local heat application, or
15 most important knowledge gaps by medical profes­ both)?
sionals but was included because of its high ranking by Should NSM be done in male patients with breast cancer? 5·2% 5·00
patient advocates. Two questions (What are the IBBR=implant-based breast reconstruction. OPS=oncoplastic breast-conserving surgery. NSM=nipple-sparing
indications for the use of one-stage vs two-stage implant- mastectomy. SSM=skin-sparing mastectomy. *Recommendation to discuss this knowledge gap at the consensus
based breast reconstruction [IBBR]?; What are the conference. †Ranking of importance of every knowledge gap on a 9-point Likert scale from 1 (not important) to
9 (extremely important). Importance was defined as the urgent need of knowledge to guide clinical practice and
indications for contralateral prophylactic mastectomy?)
research. ‡This question was not ranked among the 15 most important knowledge gaps by patient advocates but was
were not ranked among the 15 most important knowledge included because of high ranking by medical professionals. §This question was included in the 15 most important
gaps by patient advocates but were included because of knowledge gaps by reprioritisation during the second Delphi round. ¶This question was not ranked among the
high ranking by medical professionals. One of these 15 most important knowledge gaps by medical professionals but was included because of high ranking by patient
advocates. ||This question dropped out of the 15 most important knowledge gaps because of low ranking by medical
questions (What are the indications for contralateral professionals. **This question dropped out of the 15 most important knowledge gaps because of low ranking by
prophylactic mastectomy?) was included in the 15 most patient advocates.
important knowledge gaps only because of reprioritisation
Table 1: Final ranking of knowledge gaps in oncoplastic surgery prioritised during the Delphi process
during round two.
Seven OPBC research priorities were selected by
consensus during the conference (table 2). The iterative promptly accepted, the discussion on the study design
discussion and voting process (appendix p 51) achieved mirrored the previous question. Revoting achieved con­
consensus on the appropriate research method to address sensus on a prospective observational design to optimally
six of the research priorities and a strong majority on address the first two knowledge gaps.
appropriate research methods for one priority (table 3).
What are the indications for the use of synthetic mesh
What is the optimal type of reconstruction in the versus biological mesh versus no mesh in IBBR?
setting of planned adjuvant radiotherapy? This knowledge gap ranked fifth in the Delphi process
This top-ranked knowledge gap was selected as a research and was only selected as a research priority by revoting
priority by 98% of conference participants and the after a discussion of the limitations of any particular study
corresponding research question in the PICO format was design in specifically evaluating indications of one device
also readily accepted.12 However, the most appropriate versus another device. The panel agreed to address this
research strategy for this knowledge gap was heavily knowledge gap with a research question focused on
debated. An RCT design, as suggested by the expert patient satisfaction with initial use of any type of mesh, as
representatives, was not felt to be feasible because of opposed to the comparison of different types of mesh.
patient preference and surgeon bias that precludes Panellists recommended a pragmatic, non-inferiority RCT
adequate surgical equipoise. Therefore, the study design design with the satisfaction with breast scale (BREAST-Q)
selected was a prospective cohort study with propensity as a long-term, patient-reported primary outcome, strati­
score matching and patient-reported satisfaction with the fied by breast size and degree of breast ptosis.
reconstructed breast, assessed by the BREAST-Q question­
naire at 2 years, as the primary outcome. BREAST-Q is the What are the indications for the use of prepectoral
first validated questionnaire assessing patient-reported versus subpectoral IBBR?
outcomes (PROs) in breast reconstruction. This design This knowledge gap was the first to be unanimously
was endorsed by 79% of panellists. accepted as an OPBC research priority together with a
consensus recommendation for the most appropriate
What is the optimal timing of reconstruction in the research question and trial design at initial voting. The
setting of planned adjuvant radiotherapy? panel recommended a pragmatic superiority RCT to
This knowledge gap ranked second during the Delphi address the question of whether patients undergoing
process and was added to the OPBC research agenda with prepectoral IBBR are more satisfied, in terms of breast
strong consensus at initial voting during the conference. satisfaction scale scores measured by the BREAST-Q,
Although the corresponding PICO question was also than patients undergoing subpectoral IBBR.

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What are the best tools to measure the effect of

Total number Yes No Abstain Final recommendation
of votes rate (%)* oncoplastic breast-conserving surgery on QOL and to
allow the comparison of trial results?
What is the optimal type of 59 58 1 0 98% (consensus)
reconstruction in the setting of The panel included this knowledge gap in the OPBC
planned adjuvant radiotherapy? research agenda with direct consensus at initial voting.
What is the optimal timing of 60 51 6 3 85% (consensus) Panellists recom­mended a similar method to the one
reconstruction in the setting of used for this Review, consisting of a Delphi process done
planned adjuvant radiotherapy?
on the basis of a systematic review or meta-analysis,
What is the effect of OPS on local 59 26 31 2 44% (no consensus)
recurrence risk?
followed by a con­sensus conference. Both components
should involve patient advocates.
What is the effect of modern 60 26 31 3 43% (no consensus)
radiotherapy on local recurrence risk
after OPS, in general, and the role of What are the most accurate quality indicators in
partial irradiation and radiotherapy oncoplastic breast-conserving surgery?
boost, when larger margins are
achieved, in particular?† Despite considerable overlap between this question and
What are the indications for the use 58 50 8 0 86% (consensus) the preceding knowledge gap about the best tools for QOL
of synthetic mesh versus biological assessments, the panel accepted this gap as a research
mesh versus no mesh in IBBR? priority because aesthetic results and QOL are not the only
What are the indications for use of 60 52 3 5 87% (consensus) relevant quality indicators. The panel discussed how the
prepectoral versus subpectoral
disadvantages of oncoplastic breast-conserving surgery
IBBR?
should be monitored, especially because this procedure is
What is the effect of OPS on quality 59 56 3 0 95% (consensus)
of life? more complex and has a higher risk of complications and
What is the clinical relevance of 60 42 17 1 70% (majority) morbidity compared with conventional breast-conserving
anaplastic large cell lymphoma surgery. The panel recommended that the risk of compli­
associated with breast implants?† cations should be further evaluated in prospective, multi­
What are the best tools to measure 60 51 7 2 85% (consensus) centre cohort studies before a decision is made on the
the effect of OPS on quality of life
and to allow the comparison of trial
most accurate quality indicators in oncoplastic breast-
results? conserving surgery.
What are the indications for the use 59 40 18 1 68% (majority)
of one-stage versus two-stage Discussion
IBBR?† First, we identified various important knowledge gaps in
What are contraindications for nipple 59 39 18 2 66% (majority) the field of oncoplastic breast surgery. This process
preservation?†
resulted in recommendations for appropriate research
What are the most accurate quality 58 46 12 0 79% (consensus)
indicators in OPS? strategies to approach these gaps. The optimal type and
What are the best localisation 59 15 41 3 25% (no consensus)
timing of reconstruction after nipple-sparing mastectomy
techniques for non-palpable tumours or skin-sparing mastectomy with planned radiotherapy
in OPS? were considered the most important knowledge gaps and
What are the indications for 59 28 31 0 47% (no consensus) correspond to areas of controversy in the published
contralateral prophylactic
literature. Radiotherapy has a major effect on the risk of
mastectomy?†
complications after immediate IBBR and after autologous
What are the advantages of OPS 60 41 18 1 68% (majority)
compared with conventional breast reconstruction.14,15 A large, prospective, multicentre
breast-conserving surgery?† cohort study compared the complications and PROs of
patients who received reconstruction and were either
IBBR=Implant-based breast reconstruction. OPBC=Oncoplastic Breast Consortium. OPS=Oncoplastic breast-conserving
surgery. *Recommendation to include this knowledge gap in the OPBC research agenda on the basis of the gap’s irradiated or not irradiated.16 Autologous reconstruction,
importance. Majority was defined by agreement among 51–75% of the panellists and consensus by agreement of more which is often not offered by reconstructive surgeons
than 75%. Importance was defined as the urgent need of knowledge to guide clinical practice and research. in this context, was associated with a lower risk of
†As prespecified in the protocol, discussion and revoting were encouraged in the case of initial majority voting
(appendix p 4).
complications and higher patient satisfaction compared
with IBBR. Other studies have supported these obser­
Table 2: Selection of research priorities from the 15 most important knowledge gaps by the OPBC panel vations, but major controversy persists concerning the
use of immediate autologous reconstruction in this
setting.17–21 Indeed, several studies have also assessed
What is the effect of oncoplastic breast-conserving complication rates, aesthetic results, and QOL after
surgery on QOL? imme­ diate IBBR in the context of radiotherapy, with
The panel added this knowledge gap to the agenda with different timing strategies for two-stage immediate
a prompt consensus recommendation to address it by a IBBR.22,23 The recommended OPBC studies, together with
prospective, multicentre cohort study with propensity other planned or ongoing prospective observational
score matching and the satisfaction with breast scale studies and RCTs (ACTRN12614000045617, NCT03261323,
(BREAST-Q) as the primary end­point. NCT03730922, and NCT03743324) will help to select the

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Research question in PICO format Study Design Total Yes No Abstain Final
number of recommendation
votes rate (%)
Population Intervention Comparison Outcome of
interest
What is the optimal Patients with Immediate Immediate Are patients more Prospective cohort study 58 46 11 1 79% (consensus)
type of breast cancer prepectoral autologous satisfied with the with propensity score
reconstruction in who require implant, radiation, reconstruction reconstructed matching and 2 years of
the setting of mastectomy exchange to breast at 2 years follow-up; primary outcome
planned adjuvant and will need autologous after mastectomy? is the satisfaction with
radiotherapy? PMRT reconstruction breast (BREAST-Q)
What is the optimal Patients with Immediate Delayed Are patients more Prospective register with 57 47 7 3 82% (consensus)
timing of breast cancer reconstruction reconstruction satisfied with their 2 years of follow-up;
reconstruction in who require (stratified by (could have a breasts? primary outcome is the
the setting of mastectomy technique) temporary satisfaction with breast
planned adjuvant and will need tissue (BREAST-Q)
radiotherapy? PMRT expander)
What are the Patients Immediate Prepectoral Are patients less Pragmatic non-inferiority 57 40 12 5 70% (majority)
indications for use undergoing prepectoral implant satisfied with the RCT with 1:1 randomisation
of synthetic mesh mastectomy implant reconstruction reconstructed and 3 years of follow-up;
versus biological reconstruction with ADM or breast? primary outcome is the
mesh versus no without ADM or synthetic mesh satisfaction with breast
mesh in IBBR? synthetic mesh (BREAST-Q)
What are the Patients Immediate Immediate Are patients more Pragmatic superiority RCT 56 47 5 4 84% (consensus)
indications for the undergoing prepectoral subpectoral satisfied with the with 1:1 randomisation and
use of prepectoral mastectomy implant implant reconstructed 2 years of follow-up;
versus subpectoral reconstruction reconstruction breast? primary outcome is the
IBBR? satisfaction with breast
(BREAST-Q)
What is the effect of Patients after Level II* OPS Standard BCS Are patients more Prospective multicentre 55 53 2 0 96% (consensus)
OPS on quality of level II* OPS and satisfied with their cohort study with
life? mastectomy breasts? propensity matching;
primary endpoint is the
satisfaction with breast
(BREAST-Q)
What are the best NA NA NA NA Systematic review 58 44 8 6 76% (consensus)
tools to measure the (meta-analysis), a Delphi
effect of OPS on process including patients,
quality of life and to and a consensus conference
allow the with patients and surgeons
comparison of trial
results?
What are the most Patients after OPS Standard BCS Do patients have Prospective multicentre 58 52 6 0 90% (consensus)
accurate quality undergoing or mastectomy more cohort study with the
indicators in OPS? OPS complications? endpoints of complication
rate, sick leave, delays in
returning to work, and rates
of returning to theatre

ADM=acellular dermal matrix. BCS=breast-conserving surgery. IBBR=implant-based breast reconstruction. N=not applicable. OPBC=Oncoplastic Breast Consortium. OPS=oncoplastic breast-conserving surgery.
PICO=population, intervention, comparison, outcome of interest. PMRT=post-mastectomy radiotherapy. RCT=randomised controlled trial. *According to the classification by Clough and colleagues.13

Table 3: Research priorities with corresponding research question and study design as recommended by the OPBC panel during the consensus conference

optimal type and timing of reconstruction when Second, we identified the role of adjunctive mesh and
radiotherapy is planned. There has been renewed interest the positioning of implants in relation to the pectoral
in preoperative radiotherapy as a strategy to reduce the muscle during IBBR as important knowledge gaps. The
risk of toxicity induced by radiation to the reconstructed availability of acellular dermal matrix and synthetic
breast and potentially improve the accuracy of dose meshes for soft tissue coverage has triggered the increased
delivery to the tumour tissue.24 Several observational use of one-stage, immediate IBBR and, sub­ sequently,
studies with long-term follow-ups support the concept prepectoral approaches.28–34 To date, to our knowledge, all
that radiotherapy followed by mastectomy (with or published studies on prepectoral IBBR have been small
without immediate breast reconstruction) is safe and and observational and most have suggested that this
does not create technical difficulties with subsequent method is safe and effective.29–31,35–38 However, subpectoral
surgical dissection, such as making the plane of dissection IBBR remains the most common type of breast
unclear.25–27 reconstruction in the USA.39 Several prospective studies to

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 Review

IBBR after nipple-sparing mastectomy or skin-sparing

Search strategy and selection criteria mastectomy. This RCT will test the hypothesis that
After the expert representatives had constructed a list of knowledge gaps, and to identify prepectoral IBBR is associated with improved long-term
published literature in the field of oncoplastic breast surgery that might indicate whether a QOL. The primary endpoint will be patient-reported chest
knowledge gap had already been well addressed, GM and MR did a specific PubMed search physical wellbeing (ie, the overall comfort of the chest wall
on Jan 25, 2019, using the search terms: “inconclusive”[tiab] OR “unknown”[tiab] OR reconstruction), measured by the BREAST-Q. The trial
“further research”[tiab] OR “research need”[tiab] OR “gap”[tiab] OR “priority”[tiab] OR will include 372 patients across 21 OPBC sites in seven
“unmet”[tiab]) AND “skin AND mastectomy” OR “nipple AND mastectomy” OR countries with 24 months of follow-up. Initiation of the
(“mammaplasty”[MeSH]) OR (“oncoplastic” OR “oncoplastic surgery” OR “oncoplastic first study site occurred on May 28, 2020. Random assign­
technique” OR “oncoplastic breast conservation” OR “oncoplastic breast reduction” OR ment of the first patient is planned for August, 2020. The
“oncoplastic breast surgery” OR “oncoplastic approaches” OR “oncoplastic techniques”) OR trial was designed by applying the PRagmatic Explanatory
(“therapeutic mammaplasty” OR mammaplasties OR mammoplasty OR mammoplasties) Continuum Indicator Summary 2 (known as PRECIS-2)
OR (“breast conserving surgery” OR “partial breast reconstruction” OR “conservative breast require­ments for pragmatism, of which is in accordance
surgery” OR “Breast Conservation Therapy” OR “oncoplastic approach”[tiab]). GM and MR with the current panel recommendation.40–43 The study
searched ClinicalTrials.gov (using search terms “breast cancer” for condition and disease design allows surgeons flexibility in the technical aspects
and “nipple-sparing”, or “skin-sparing”, or “oncoplastic”) to obtain information on of surgical decision making, which might help to avoid
ongoing clinical trials indicating that knowledge gaps might be sufficiently addressed in some of the safety issues that were encountered in the
the near future. The expert representatives adjusted and finalised the list of knowledge BRIOS trial.7,8 Although the results of the trial showed no
gaps. The results of the Delphi process and consensus conference were brought into major differences in patient QOL and satisfaction when
context with published, ongoing, or planned studies in the form of this Review. Literature com­paring one-stage versus two-stage immediate IBBR,
searches were developed, peer reviewed, and done by two information specialists, Hannah the acellular dermal matrix-assisted one-stage approach
Ewald and Christian Appenzeller-Herzog (University Medical Library, University of Basel, was associated with significantly higher odds of compli­
Basel, Switzerland). We searched MEDLINE, Embase, and Epistemonikos for randomised cations, re-operation, and loss of implant, acellular dermal
controlled trials, systematic reviews, and meta-analyses either published between matrix, or both. Despite these high rates of complications
database inception and Sept 13, 2019, (MEDLINE) or between database inception and being partly explained by poor patient selection and lack of
Sept 17, 2019, (Embase and Epistemonikos) by use of text words and subject headings for surgeon experience with a one-stage technique, the safety
terms around breast cancer or mastectomy and breast reconstruction or oncoplastic of one-stage immediate IBBR in routine surgical practice
breast-conserving surgery. We applied standardised filters for study designs, but no must be questioned.44,45
language restrictions. To identify any planned or ongoing studies, we searched Prospero, Finally, we identified the need to investigate the
ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform for study effectiveness of oncoplastic breast-conserving surgery.
information published between database inception and Sept 17, 2019. We did not apply The association between objective aesthetic outcomes
any language restrictions. The full search strategy can be found in the appendix and PROs is complex. Available evidence suggests that
(pp 36–39). In a first screening round done on abstract level, AS excluded references oncoplastic breast-conserving surgery has a modest
according to the following criteria: study not involving humans, study not on breast effect on patient satisfaction.46 An observational study
cancer, study on basic research only, study without surgical intervention, study on the from Brazil reported a significantly higher proportion of
antibiotic effect of compounds only, study on drains or sealing or dressing only, study on excellent aesthetic scores after oncoplastic breast-
decision aids for patients, and study on cost analysis only. GM and EAK independently did a conserving surgery compared with conventional breast-
second screening on abstract level and selected further references according to their conserving surgery when measured by software and
relevance to the seven selected research priorities. These references were added with surgeons.47 However, there were no differences in
full-text to an EndNote X8 library. WPW generated the final reference list from this aesthetic outcomes when these outcomes were assessed
EndNote X8 library on the basis of currency and relevance to the scope of this Review. by patients. There are at least ten commonly used PRO
Additional references cited within those publications or retrieved from personal files were metrics in breast surgery and new tools are currently
selectively included. under development (NCT02753673).48,49 Determination of
the best assessment tool will facilitate measurements of
QOL across OPBC centres in future studies.50 Available
assess the role of adjunctive mesh in different settings are options are the BREAST-Q question­naire, the European
planned or ongoing (NCT03494244, NCT02608593, and Organisation for Research and Treatment of Cancer
NCT03195322). Three RCTs com­paring prepectoral versus (EORTC) QLQ-C30, and the EORTC QLQ-BR23.51–53
subpectoral appro­ aches for immediate IBBR are However, the BREAST-Q is the most widely used tool,
registered: a three-centre trial in Denmark and Norway has been rigorously developed and validated, and is
(NCT03143335), and single-centre trials from the Mayo specific to breast surgery.54–56
Clinic (NCT02775409) and Ottawa Hospital Research Clinical indicators of risk in oncoplastic breast-
Institute (NCT03959709). The OPBC received major conserving surgery are likely to focus on factors such as
public funding from the Swiss National Science rates of complications and return to the operating room,
Foundation for the OPBC-02 PREPEC study (Swiss and delays to starting adjuvant treatments or returning to
National Science Foundation number 33IC30 185613), a work. A comprehensive review showed high rates of
large international RCT on prepectoral versus subpectoral overall survival and disease-free survival together with

e382 www.thelancet.com/oncology Vol 21 August 2020

 Review

low rates of local recurrence, positive surgical margins, ensuring that questions related to the accuracy of any part of the work
and re-excisions after oncoplastic breast-conserving are appropriately investigated and resolved.
surgery.57 Thus, conventional, oncological variables do not Declaration of interests
seem to be discriminatory as crucial quality indicators.57 WPW received support paid to University Hospital Basel for in-house
conferences and meetings from Sandoz, Genomic Health, Medtronic,
Another large review found a wide range of complications and Novartis Oncology. MM declares honoraria from Roche and
after oncoplastic breast-conserving surgery with largely Genomic Health. AP is a co-developer of BREAST-Q, FACE-Q, and
differing risks because of poorly designed and under­ BODY-Q, which are owned by Memorial Sloan Kettering Cancer Center,
powered studies.4 The absence of standardised practice and receives license fee payments for the use of BREAST-Q, FACE-Q,
and BODY-Q in industry-sponsored clinical trials. RS reports personal
in oncoplastic breast-conserving surgery hampers the fees from the Oncoplastic Breast Consortium during the conduct of the
generation of robust clinical data in this field. Despite study. FF reports support from Roche, Novartis, AstraZeneca, Pfizer,
knowledge gaps referring to classification systems for and Bondimed, is an editor for Oncoplastic Surgery and an inventor of
oncoplastic breast-conserving surgery being ranked the breast analyzing tool. JH is supported by a pfm medical and mentor
grant, and reports support from Roche, Celgene, BARD, Somatex, BIP
relatively low (27th and 30th of 38 gaps) in this Delphi medical, and Devicor. SP is funded by a National Institute for Health
process, standardisation to permit comparative research, Research Clinician Scientist award. All other authors declare no
meaningful guidelines, and accreditation of training competing interests.
programmes is urgently needed.10,13,58–60 Specific risks asso­ Acknowledgments
ciated with the various techniques need to be identified to The consensus meeting held for all panellists in Basel, Switzerland, on
Sept 12, 2019, was supported by the Swiss Cancer League, the Swiss
support the development of quality assurance program­
Cancer Research Foundation, the Claudia von Schilling Foundation for
mes for oncoplastic breast-conserving surgery that are Breast Cancer Research, the Swiss Group for Clinical Cancer Research
standardised. and Pfizer Award 2019, Sandoz, Genomic Health, and Medtronic. We also
acknowledge both financial and in-kind support provided by University
Conclusion Hospital Basel. No funders of the study were involved in the selection of
topics, in the choice of panellists, in the collection, analysis, and
The 2019 OPBC Delphi process and consensus interpretation of data, in the writing of the report, or in the decision to
conference resulted in three recommendations. First, submit for publication. We thank our medical information specialists
the optimal type and timing of reconstruction after Hannah Ewald and Christian Appenzeller-Herzog from University
Medical Library, University of Basel, Basel, Switzerland.
nipple-sparing mastectomy or skin-sparing mastectomy
with planned radiotherapy should be addressed by References
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