O-087 Use and safety of assisted reproductive technology in young BRCA carriers with a pregnancy after treatment for breast cancer: results from an international cohort study
Authors: Magaton I M , Blandeaux E , Hamy A S , Linn S , Bernstein-Molho R , Peccatori F A , Ferrari A , Agostinetto E , Venturelli M , Vaz-Duarte-Luis I M , Rodriguez-Wallberg K A , Demeestere I , Azim H A , Partridge A H , Lambertini M 
Published: July 2024

Abstract

Study question
Does assisted reproductive technology (ART) to achieve pregnancy after breast cancer (BC) adversely affect maternal or fetal outcomes in germline BRCA1/2 pathogenic variants (PVs) carriers?

Summary answer
This global study showed that ART is safe in BC survivors harboring BRCA1/2 PVs, with no apparent worsening of maternal prognosis or fetal outcomes.

What is known already
Very little information is currently available on the safety of fertility treatments in BC survivors harboring BRCA1/2 PVs. The previous published work on this topic included only 22 cases of patients who used any kind of ART to become pregnant; the small number of included patients did not allow for statistical analysis. Hence, concerns remain among physicians counseling young BRCA carriers with prior history of BC on the safety of using ART to attempt pregnancy

Study design, size, duration
International, multicenter, hospital-based, retrospective cohort study across 78 centers worldwide. The study included 4732 women harboring known BRCA1/2 PVs and diagnosed at ≤ 40 years with stage I-III BC between January 2000 and 2020 (Lambertini M et al., JAMA 2024;331:49-59). This specific analysis included 543 women with a pregnancy after prior history of BC harboring a BRCA1/2 PV.

Participants/materials, setting, methods
Among 543 young BRCA carriers with a pregnancy after BC, 436 conceived naturally and 107 using ART. ART procedures included embryo transfer under hormonal replacement therapy following oocyte or embryo cryopreservation at diagnosis, treatment with oocyte donation, ovulation induction and In-Vitro-Fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) carried out after anticancer treatments. Survival analyses compared patients achieving a pregnancy spontaneously (spontaneous pregnancy group) vs. using ART (ART group).

Main results and the role of chance
Of 107 pregnancies achieved through ART, 45 (42.1%) were obtained with oocytes or embryo cryopreserved at diagnosis, 33 (30.8%) with ovarian stimulation and IVF/ICSI after completion of anticancer therapies, 21 (19.6%) with embryo transfer following oocyte donation and for 8 ART type was missing. As compared to survivors in the spontaneous pregnancy group, those in the ART group were older at the time of conception (37.1 vs. 34.3 years, p &lt; 0.001), had more often hormone receptor-positive BC (46 (43.4%) vs. 132 (30.8%), p = 0.016), and a longer median time from BC diagnosis to conception (4.2 vs. 3.3 years, p = 0.004). No statistically significant differences in pregnancy complications were observed between cohorts (p = 0.382). However, patients who conceived with ART had more miscarriages (12, 11.3%) than those who conceived spontaneously (38, 8.8%). The opposite was true for induced abortion (1 (0.9%) vs. 36 (8.3%), respectively). At a median follow up of 9.1 years (interquartile range 6.4-13.4), no detrimental effect of ART on disease-free survival (DFS) was observed with 13 DFS events observed among the 99 patients undergoing ART and 118 DFS events in patients with spontaneous pregnancy (log-rank p = 0.147).

Limitations, reasons for caution
Despite the global representation, this retrospective study included a small number of patients for this specific analysis. Nevertheless, this is the largest analysis to date investigating safety of ART in BC survivors harboring BRCA1/2 PVs.

Wider implications of the findings
Young BRCA carriers can be reassured that the use of ART to achieve pregnancy is safe. Oocyte/embryo cryopreservation in young BRCA carriers allows access to pre-implantation genetic testing, if the patients are interested.

Trial registration number
NCT03673306