Prepectoral versus subpectoral implant-based breast reconstruction after skin-sparing mastectomy or nipple-sparing mastectomy (OPBC-02/ PREPEC): a pragmatic, multicentre, randomised, superiority trial

Elisabeth A Kappos; Alexandra Schulz; Meredith M Regan; Giusi Moffa; Yves Harder; Karin Ribi; Shelley Potter; Andrea L Pusic; Mathias K Fehr; Lars G Hemkens; Thomas Holzbach; Jian Farhadi; Colin Simonson; Michael Knauer; Ralph Verstappen; Heiner C Bucher; Daniel Zwahlen; Frank Zimmermann; Matthias Schwenkglenks; Rosine Mucklow; Jane Shaw; Vesna Bjelic-Radisic; Amelia Chiorescu; Yoon S Chun; Subrina Farah; Chen Xiaosong; Linda Nigard; Sherko Kuemmel; Roland Reitsamer; Maik Hauschild; Ilario Fulco; Christoph Tausch; Thomas Fischer; Dimitri Sarlos; Mihai A Constantinescu; Judith E Lupatsch; Florian Fitzal; Joerg Heil; Zoltan Matrai; Jana de Boniface; Christian Kurzeder; Martin Haug; Walter P Weber

doi:10.1136/bmjopen-2020-045239

Prepectoral versus subpectoral implant-based breast reconstruction after skin-sparing mastectomy or nipple-sparing mastectomy (OPBC-02/ PREPEC): a pragmatic, multicentre, randomised, superiority trial

BMJ Open. 2021 Sep 2;11(9):e045239. doi: 10.1136/bmjopen-2020-045239.

Authors

Elisabeth A Kappos^{1

2

3}, Alexandra Schulz^{3

4}, Meredith M Regan⁵, Giusi Moffa⁶, Yves Harder^{7

8}, Karin Ribi⁹, Shelley Potter¹⁰, Andrea L Pusic¹¹, Mathias K Fehr¹², Lars G Hemkens^{3

4

13

14

15}, Thomas Holzbach^{16

17}, Jian Farhadi^{3

18

19}, Colin Simonson²⁰, Michael Knauer²¹, Ralph Verstappen^{22

23}, Heiner C Bucher^{3

13}, Daniel Zwahlen²⁴, Frank Zimmermann^{3

25}, Matthias Schwenkglenks^{26

27}, Rosine Mucklow^{28

29}, Jane Shaw²⁹, Vesna Bjelic-Radisic³⁰, Amelia Chiorescu^{31

32}, Yoon S Chun¹¹, Subrina Farah⁵, Chen Xiaosong³³, Linda Nigard³⁴, Sherko Kuemmel^{35

36}, Roland Reitsamer³⁷, Maik Hauschild³⁸, Ilario Fulco^{39

2

3

40}, Christoph Tausch¹⁸, Thomas Fischer⁴¹, Dimitri Sarlos⁴², Mihai A Constantinescu^{43

44}, Judith E Lupatsch²⁶, Florian Fitzal⁴⁵, Joerg Heil⁴⁶, Zoltan Matrai⁴⁷, Jana de Boniface^{32

48}, Christian Kurzeder^{39

3

49}, Martin Haug^{39

2

3}, Walter P Weber^{39

3}

Affiliations

¹ Breast Center, University Hospital Basel, University of Basel, Basel, Switzerland elisabeth.kappos@usb.ch.
² Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, Basel, Switzerland.
³ University of Basel, Basel, Switzerland.
⁴ Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
⁵ IBCSG Statistical Center, Division of Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
⁶ Department of Mathematics and Computer Science, University of Basel, Basel, Switzerland.
⁷ Department of Plastic, Reconstructive and Aesthetic Surgery, Ospedale Regionale di Lugano and Centro di Senologia della Svizzera Italiana, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland.
⁸ Faculty of Biomedical Science, Università della Svizzera Italiana (USI), Lugano, Switzerland.
⁹ Quality of Life Office, International Breast Cancer Study Group Coordinating Center, Bern, Switzerland.
¹⁰ Centre for Surgical Research, Bristol Medical School and Bristol Breast Care Centre, North Bristol NHS Trust, University of Bristol, Bristol, UK.
¹¹ Division of Plastic and Reconstructive Surgery, Department of Surgery, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹² Department of Gynecology and Obstetrics, Cantonal Hospital Frauenfeld, Frauenfeld, Switzerland.
¹³ Basel Institute for Clinical Epidemiology, University Hospital Basel, Basel, Switzerland.
¹⁴ Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA.
¹⁵ Meta-Research Innovation Center Berlin (METRIC-B), Berlin Institute of Health, Berlin, Germany.
¹⁶ Department of Hand and Plastic Surgery, Spital Thurgau AG, Frauenfeld, Thurgau, Switzerland.
¹⁷ Breast Center Thurgau, Thurgau, Switzerland.
¹⁸ Breast Center Zurich, Zurich, Switzerland.
¹⁹ Plastic Surgery Group, Switzerland.
²⁰ Brustzentrum Spital Sitten, Sitten, Switzerland.
²¹ Breast Center Eastern Switzerland, St. Gallen, Switzerland.
²² Breast Center St. Gallen, St. Gallen Cantonal Hospital, St. Gallen, Switzerland.
²³ Department of Hand, Plastic and Reconstructive Surgery, St. Gallen Cantonal Hospital, St. Gallen, Switzerland.
²⁴ Department of Radiation Oncology, Kantonsspital Winterthur, Winterthur, Switzerland.
²⁵ Department of Radiation Oncology, University of Basel, Basel, Switzerland.
²⁶ Institute of Pharmaceutical Medicine (ECPM), University of Basel, Basel, Switzerland.
²⁷ Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Zurich, Switzerland.
²⁸ Independent patient expert, Buxtorf Quality Services, Basel, Switzerland.
²⁹ Patient Advocacy Group, Oncoplastic Breast Consortium, Basel, Switzerland.
³⁰ Breast Unit, University Hospital Helios Wuppertal, University Witten Herdecke, Wuppertal, Germany.
³¹ Department of Breast, Endocrine tumours and Sarcoma, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
³² Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
³³ Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³⁴ Södersjukhuset, Bröstsektionen, Kirurgkliniken, Stockholm, Sweden.
³⁵ Breast Unit, Kliniken Essen-Mitte, Essen, Germany.
³⁶ Charité - Universitätsmedizin Berlin, Department of Gynecology with Breast Center, Berlin, Germany.
³⁷ Breast Center Salzburg, University Clinic Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria.
³⁸ Department of Gynecology and Obstetrics, Gesundheitszentrum Fricktal, Rheinfelden, Switzerland.
³⁹ Breast Center, University Hospital Basel, University of Basel, Basel, Switzerland.
⁴⁰ Breast Center, Hirslanden Clinic Aarau, Aarau, Switzerland.
⁴¹ Lindenhofgruppe, Centerclinic, Brustzentrum Bern, Bern, Switzerland.
⁴² Department of Obstetrics and Gynecology, Kantonsspital Aarau AG, Aarau, Switzerland.
⁴³ Department of Plastic and Hand Surgery, Inselspital University Hospital, Bern, Switzerland.
⁴⁴ University of Bern, Bern, Switzerland.
⁴⁵ Breast Health Center and Department of Surgery, Medical University, Vienna, Austria.
⁴⁶ Department of Obstetrics and Gynecology, University Breast Unit, University Women's Hospital Heidelberg, Heidelberg, Germany.
⁴⁷ National Institute of Oncology, Department of Breast and Sarcoma Surgery, Budapest, Hungary.
⁴⁸ Department of Surgery, Capio St. Göran's Hospital, Stockholm, Sweden.
⁴⁹ Department of Gynecology and Obstetrics, University Hospital Basel, Basel, Switzerland.

Abstract

Introduction: The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast implant above (prepectoral) or below (subpectoral) the pectoralis major muscle or by using the patients' own tissue (autologous reconstruction). The optimal positioning of the implant prepectoral or subpectoral is currently not clear. Subpectoral implant-based breast reconstruction (IBBR) is still standard care in many countries, but prepectoral IBBR is increasingly performed. This heterogeneity in breast reconstruction practice is calling for randomised clinical trials (RCTs) to guide treatment decisions.

Methods and analysis: International, pragmatic, multicentre, randomised, superiority trial. The primary objective of this trial is to test whether prepectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being (chest) compared with subpectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of breast cancer. Secondary objectives will compare prepectoral versus subpectoral IBBR in terms of safety, QoL and patient satisfaction, aesthetic outcomes and burden on patients. Total number of patients to be included: 372 (186 per arm).

Ethics and dissemination: This study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained for the lead investigator's site by the Ethics Committee 'Ethikkommission Nordwest- und Zentralschweiz' (2020-00256, 26 March 2020). The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs and good publication practice. Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories adhering to the FAIR (Findability, Accessibility, Interoperability, and Reuse) principles.

Trial registration number: NCT04293146.

Keywords: breast surgery; breast tumours; cancer genetics; gynaecological oncology; plastic & reconstructive surgery; protocols & guidelines.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Breast Implantation*
Breast Implants*
Breast Neoplasms* / surgery
Female
Humans
Mammaplasty*
Mastectomy
Nipples / surgery

Associated data

ClinicalTrials.gov/NCT04293146