Preimplantation Genetic Testing (PGT) for breast cancer

Abstract

Preimplantation genetic testing (PGT) is currently extended to an increasing number of late-onset common disorders with genetic predisposition, including inhered forms of breast and ovarian cancer (HBOC), determined by BRCA1/2 genes. Prevention and treatment of HBOC presents a real challenge, because of incomplete penetrance and variable expressivity of predisposing BRCA1/2 genes. The major problem is that preventive management may not affect penetrance of these genes, which may lead to HBOC even after prophylactic bilateral mastectomy or oophorectomy. So PGT for BRCA1/2 genes is an extremely attractive approach, as it allows not only avoiding the transfer of mutant embryos, but also provides the possibility of having children free from predisposition to HBOC. The present paper summarizes the first systematic experience of 149 PGT cycles for BRCA1/2 gene mutations, which resulted in birth of 68 healthy, disease predisposition free children, demonstrating important clinical implications of PGT as practical means for couples carrying BRCA1/2 predisposing genes.

Clinical outcomes of preimplantation genetic testing for hereditary cancer syndromes: A systematic review

“…The process of PGT‐M accompanied by PGT‐A has been referred to as ‘combined PGT’ 15 . In our review, 10 studies made any mention of aneuploidy testing, although only 4 studies used rigorous approaches to PGT‐A, such as next‐generation 24‐chromosome aneuploidy screening 20,26,30,32 . In addition, the use of PGT‐A within these studies was not universally applied to all patients.…”

“…15 In our review, 10 studies made any mention of aneuploidy testing, although only 4 studies used rigorous approaches to PGT-A, such as next-generation 24-chromosome aneuploidy screening. 20,26,30,32 In addition, the use of PGT-A within these studies was not universally applied to all patients. Although PGT-A has been reported to increase LBR during IVF, 42 we did not have enough information to determine the impact of PGT-A in our review given the limited number of studies that clearly documented its use and the variable application within studies.…”

“…18 The remaining four studies used more rigorous approaches, including next-generation 24chromosome aneuploidy screening 20,26,32 or a variety of approaches based on the best technology available at the time (e.g., FISH, PCR, array-CGH, 24-chromosome aneuploidy screening). 30 However, the application of aneuploidy testing in these four studies was not universal, with a weighted mean use of 42% (71 of 168 patients, range:…”

“…This systematic review has some limitations. For HBOC studies, only two studies reported enough information to calculate CPR and LBR on a per‐embryo basis 18,30 ; therefore, our calculations may not be an accurate representation of the true CPR and LBR among patients with HBOC. For studies on HCS other than HBOC, the number of participants was limited; aside from Merker et al.…”

“…analysis of the false-negative rates of PGT-M. Nine of 15 publications directly or indirectly reported no false-negatives in their study, 13,15,17,19,22,24,30,31,33 but only four described how that testing was performed (i.e., postnatally 17,19 or prenatally). 22,33 One publication performed post-PGT-M reanalysis of all embryos, which showed concordant results.…”