BACKGROUND AND AIMS
Quality of life for cancer survivors has become a priority in cancer care and research. Almost 50% of the young patients who have survived breast cancer (BC) have expressed their desire to become pregnant.1Several studies have demonstrated the safety of pregnancy in BC survivors2 and the safety of ovarian stimulation for oocytes cryopreservation in order to preserve fertility, as advised by oncological guidelines.3,4However, many patients face infertility after neoadjuvant BC therapy and would require fertility treatments (FT) in order to achieve a pregnancy. Nevertheless, the safety of FT after BC remission is still unclear, as there is poor evidence on the prognostic impact of increased oestrogen exposure induced by FT not followed by anticancer treatments,5,6 even in endocrine-sensitive disease. Yet infertility remains common following systemic treatment. To date, only two small studies have evaluated the safety of assisted reproductive technology, leading to discordant attitudes. Therefore, the safety of FT in BC survivors urgently requires further investigation.
MATERIALS AND METHODS
The authors conducted a retrospective, multicentre study including BC survivors <40 years old at BC diagnosis who underwent FT between January 2006 and December 2016. They were compared to a nonexposed (NE) group of BC survivors who did not perform FT, matched (2:1) for BRCA status, BC stage, anticancer treatment, length of disease-free period (not inferior to the time between BC diagnosis and first FT in the FT group), and age at diagnosis when feasible. Patients with Stage IV cancer at diagnosis, BC during pregnancy, pre-existing neoplasia, or ovarian failure at BC diagnosis were excluded. FT included controlled ovarian stimulation, clomiphene citrate ovulation induction, and hormone replacement therapy for embryo transfer.
Nine fertility centres and two oncologic centres in Belgium participated in the study. A total of 39 eligible patients were matched with 73 NE patients, as appropriate matching 2:1 was not feasible for five patients carrying BRCA mutations. No statistical difference was found between the two groups for BRCA mutation status, BC stage, oestrogen and progesterone receptors, HER2 status, use of chemotherapy, or adjuvant endocrine therapy. However, differences were observed for age at diagnosis (mean 31.8 [3.9] versus 34.3 [3.6] years in the FT and NE groups, respectively; p<0.001) and nulliparity at diagnosis (89.7% versus 46.6% in the FT and NE groups, respectively; p<0.001). Median follow-up time from BC diagnosis was 9 (4–22) and 12 (6–19) years in the FT and NE groups, respectively (p=0.004). FT were performed at a mean age of 37.1 (4.6) years. During FT, the median oestrogen peak level was 696.5 pg/mL (139.7–4,130.0). In the FT group, 59% conceived after BC versus 26% in the NE group (p=0.001). To evaluate the impact of FT exposure on oncological outcomes, the time of the first FT exposure was used as a starting point and the follow-up time was adjusted accordingly for matched patients in the NE group. BC relapsed in 7.7% in FT versus 20.5% in NE groups (hazard ratio: 0.46; 95% confidence interval: 0.13–1.60; p=0.23); median relapse time was 1.3 years (range: 0.3–2.7) after FT versus 4.5 years (range: 0.4–11.1) in the NE group following FT adjusted time (p=0.14).
This is the largest reported cohort of BC survivors having undergone FT following the completion of oncological treatments. This study provides reassuring evidence based on long median follow-up, showing that FT are safe in BC survivors who had an early stage disease, a good prognosis, and an unfulfilled desire for pregnancy.