Early salpingectomy (TUbectomy) with delayed oophorectomy to improve quality of life as alternative for risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers (TUBA study): a prospective non-randomised multicentre study.
BACKGROUND
Risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 is currently recommended to BRCA1/2 mutation carriers. This procedure decreases the elevated ovarian cancer risk by 80-96% but it initiates premature menopause as well. The latter is associated with short-term and long-term morbidity, potentially affecting quality of life (QoL). Based on recent insights into the Fallopian tube as possible site of origin of serous ovarian carcinomas, an alternative preventive strategy has been put forward: early risk-reducing salpingectomy (RRS) and delayed oophorectomy (RRO). However, efficacy and safety of this alternative strategy have to be investigated.


METHODS
A multicentre non-randomised trial in 11 Dutch centres for hereditary cancer will be conducted. Eligible patients are premenopausal BRCA1/2 mutation carriers after completing childbearing without (a history of) ovarian carcinoma. Participants choose between standard RRSO at age 35-40 (BRCA1) or 40-45 (BRCA2) and the alternative strategy (RRS upon completion of childbearing and RRO at age 40-45 (BRCA1) or 45-50 (BRCA2)). Women who opt for RRS but do not want to postpone RRO beyond the currently recommended age are included as well. Primary outcome measure is menopause-related QoL. Secondary outcome measures are ovarian/breast cancer incidence, surgery-related morbidity, histopathology, cardiovascular risk factors and diseases, and cost-effectiveness. Mixed model data analysis will be performed.


CONCLUSIONS
The exact role of the Fallopian tube in ovarian carcinogenesis is still unclear. It is not expected that further fundamental research will elucidate this role in the near future. Therefore, this clinical trial is essential to investigate RRS with delayed RRO as alternative risk-reducing strategy in order to improve QoL.


BACKGROUND
ClinicalTrials.gov ( NCT02321228 ).
Department of Obstetrics & Gynaecology, Radboud University Medical Center, PO Box 9101, , 6500 HB, Nijmegen, The Netherlands. Marline.Harmsen@radboudumc.nl.
Marline G
MG
Harmsen
Department of Obstetrics & Gynaecology, Radboud University Medical Center, PO Box 9101, , 6500 HB, Nijmegen, The Netherlands. Marieke.Arts-deJong@radboudumc.nl.
Marieke
M
Arts-de Jong
Department of Human Genetics, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. Nicoline.Hoogerbrugge@radboudumc.nl.
Nicoline
N
Hoogerbrugge
Department of Cardiology, Radboud University Medical Center, PO Box 9101, , 6500 HB, Nijmegen, The Netherlands. Angela.Maas@radboudumc.nl.
Angela H E M
AH
Maas
Department of Medical Psychology, Radboud University Medical Center, PO Box 9101, , 6500 HB, Nijmegen, The Netherlands. Judith.Prins@radboudumc.nl.
Judith B
JB
Prins
Department of Pathology, Radboud University Medical Center, PO Box 9101, , 6500 HB, Nijmegen, The Netherlands. Hans.Bulten@radboudumc.nl.
Johan
J
Bulten
Department for Health Evidence, Radboud University Medical Center, PO Box 9101, , 6500 HB, Nijmegen, The Netherlands. Steven.Teerenstra@radboudumc.nl.
Steven
S
Teerenstra
Department for Health Evidence, Radboud University Medical Center, PO Box 9101, , 6500 HB, Nijmegen, The Netherlands. Eddy.Adang@radboudumc.nl.
Eddy M M
EM
Adang
Gynaecologic Oncologic Center South location Elisabeth-TweeSteden Hospital, Dr. Deelenlaan 5, 5042 AD, Tilburg, The Netherlands. Jurgen.Piek@catharinaziekenhuis.nl.|Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. Jurgen.Piek@catharinaziekenhuis.nl.
Jurgen M J
JM
Piek
Department of Gynaecology, Erasmus MC Cancer Clinic, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. H.vanDoorn@erasmusmc.nl.
Helena C
HC
van Doorn
Center for Gynaecological Oncology Amsterdam (CGOA), Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. M.v.Beurden@nki.nl.
Marc
M
van Beurden
Department of Gynaecology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. M.J.E.Mourits@umcg.nl.
Marian J E
MJ
Mourits
Department of Gynaecological Oncology, UMC Utrecht Cancer Centre, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. R.Zweemer@umcutrecht.nl.
Ronald P
RP
Zweemer
Department of Obstetrics and Gynaecology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. K.N.Gaarenstroom@lumc.nl.
Katja N
KN
Gaarenstroom
Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands. Brigitte.Slangen@mumc.nl.
Brigitte F M
BF
Slangen
Gynaecologic Oncologic Center South, Elisabeth-TweeSteden Hospital, Hilvarenbeekseweg 60, 5022 GC, Tilburg, The Netherlands. C.Vos@elisabeth.nl.
M Caroline
MC
Vos
Center for Gynaecological Oncology Amsterdam (CGOA), AMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. L.R.vanLonkhuijzen@amc.uva.nl.
Luc R C W
LR
van Lonkhuijzen
Department of Obstetrics & Gynaecology, Radboud University Medical Center, PO Box 9101, , 6500 HB, Nijmegen, The Netherlands. Leon.Massuger@radboudumc.nl.
Leon F A G
LF
Massuger
Scientific Institute for Quality of Healthcare, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. Rosella.Hermens@radboudumc.nl.
Rosella P M G
RP
Hermens
Department of Obstetrics & Gynaecology, Radboud University Medical Center, PO Box 9101, , 6500 HB, Nijmegen, The Netherlands. Joanne.deHullu@radboudumc.nl.
Joanne A
JA
de Hullu
D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008594:Menopause, Premature / Q000523:psychology*; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D010052:Ovariectomy / Q000009:adverse effects / Q000191:economics / Q000379:methods; D011788:Quality of Life; D058994:Salpingectomy / Q000009:adverse effects / Q000191:economics / Q000379:methods*
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human