title: Hereditary breast and ovarian cancer and reproduction: an observational study on the suitability of preimplantation genetic diagnosis for both asymptomatic carriers and breast cancer survivors.
abstract: Preimplantation genetic diagnosis (PGD) is a reproductive option for BRCA1/2 mutation carriers wishing to avoid transmission of the predisposition for hereditary breast and ovarian cancer (HBOC) to their offspring. Embryos obtained by in vitro fertilisation (IVF/ICSI) are tested for the presence of the mutation. Only BRCA-negative embryos are transferred into the uterus. The suitability and outcome of PGD for HBOC are evaluated in an observational cohort study on treatments carried out in two of Western-Europe's largest PGD centres from 2006 until 2012. Male carriers, asymptomatic female carriers and breast cancer survivors were eligible. If available, PGD on embryos cryopreserved before chemotherapy was possible. Generic PGD-PCR tests were developed based on haplotyping, if necessary combined with mutation detection. 70 Couples underwent PGD for BRCA1/2. 42/71 carriers (59.2 %) were female, six (14.3 %) of whom have had breast cancer prior to PGD. In total, 145 PGD cycles were performed. 720 embryos were tested, identifying 294 (40.8 %) as BRCA-negative. Of fresh IVF/PGD cycles, 23.9 % resulted in a clinical pregnancy. Three cycles involved PGD on embryos cryopreserved before chemotherapy; two of these women delivered a healthy child. Overall, 38 children were liveborn. Two BRCA1 carriers were diagnosed with breast cancer shortly after PGD treatment, despite negative screening prior to PGD. PGD for HBOC proved to be suitable, yielding good pregnancy rates for asymptomatic carriers as well as breast cancer survivors. Because of two cases of breast cancer shortly after treatment, maternal safety of IVF(PGD) in female carriers needs further evaluation.
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre +, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: Inge A P
authors.initials: IA
authors.lastname: Derks-Smeets
authors.forename: Christine E M
authors.initials: CE
authors.lastname: de Die-Smulders
authors.forename: Shari
authors.initials: S
authors.lastname: Mackens
authors.forename: Ron
authors.initials: R
authors.lastname: van Golde
authors.forename: Aimee D
authors.initials: AD
authors.lastname: Paulussen
authors.forename: Jos
authors.initials: J
authors.lastname: Dreesen
authors.forename: Herman
authors.initials: H
authors.lastname: Tournaye
authors.forename: Pieter
authors.initials: P
authors.lastname: Verdyck
authors.forename: Vivianne C G
authors.initials: VC
authors.lastname: Tjan-Heijnen
authors.forename: Madelon
authors.initials: M
authors.lastname: Meijer-Hoogeveen
authors.forename: Jacques
authors.initials: J
authors.lastname: De Greve
authors.forename: Joep
authors.initials: J
authors.lastname: Geraedts
authors.forename: Martine
authors.initials: M
authors.lastname: De Rycke
authors.forename: Maryse
authors.initials: M
authors.lastname: Bonduelle
authors.forename: Willem M
authors.initials: WM
authors.lastname: Verpoest
mesh_terms: D000328:Adult; D058070:Asymptomatic Diseases; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D010051:Ovarian Neoplasms / Q000175:diagnosis*; D011247:Pregnancy; D011256:Pregnancy Outcome; D019836:Preimplantation Diagnosis; D011296:Prenatal Diagnosis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human