P-376 Letrozole to minimise exposure to elevated serum estradiol during superovulation for breast cancer patients prior to chemotherapy. Real world experience from a statewide oncofertility service
Authors: Kiely N , Arulpragasam K , Vasihnav T , Spiteri J , Sweeten P , Ledger W 
Published: July 2024

Abstract

Study question
How effective is co-treatment with letrozole in supressing peak E2 in a real world setting?

Summary answer
We observed greater than anticipated supra-physiological serum estadiol concentrations in our cohort.

What is known already
Breast cancer occurs frequently in women of reproductive age, many of whom request oocyte or embryo cryopreservation before chemo/radiotherapy. Oncofertility treatment requires superovulation with resultant elevation of serum estradiol above concentrations seen physiologically. In order to avoid possible stimulation of estrogen receptor positive breast cancers, co-administration of letrozole is frequently recommended. A 67% lower mean serum estradiol in a letrozole treated group compared with an untreated superovulated comparison group has been reported in the literature, suggesting a protective mechanism. Peak E2 concentration across 4 cohorts of patients co-treated with letrozole has been reported to be 103 – 2350 (mean 564).

Study design, size, duration
We performed a retrospective cohort study of women referred for fertility preservation following diagnosis of breast cancer to the Fertility Research Centre at The Royal Hospital for Women, Sydney between Jan 2020 and Jan 2024. Women were identified from hospital outpatient paper and electronic medical records. 145 new referrals were received by our centre, with 88 patients undergoing 107 cycles.

Participants/materials, setting, methods
145 women aged between 19 and 44 with newly diagnosed breast cancer were referred to our Statewide, multidisciplinary, public oncofertility service for consideration of treatment and review at our fertility multidisciplinary team meeting.
Our oncofertility database and outpatient clinical records were used to identify new referrals to the service. Electronic and paper medical records including the ART database were used to obtain cycle information, blood results and demographic information

Main results and the role of chance
Peak estradiol concentrations (pMol/L)
35% of cycles resulted in peak E2 &gt; 2000. 11% of cycles resulted in peak E2 &gt; 4000 and 2% of cycles resulted in peak E2 &gt; 7000. We calculated a mean E2 of 1837.
The mean anti-mullerian hormone was 20.3 pMol/L and mean antral follicle count 19.7. The mean BMI was 24.7. The average stimulation length was 13 days (7-16 days) with an average cumulative gonadotrophin dose of 2769 IU.
Average number of MII oocytes per cycle was 7.2. 16 % of patients elected to preserve embryos. The fertilisation rate was 50%, with 61% of fertilised eggs resulting in frozen blastocytes. There have been 2 pregnancies and one live birth to date. 32% of cycles had a germline genetic result prior to OPU, with 20% having a positive BRCA gene mutation.
Breast cancer hormone status
56% were Estrogen Receptor positive. 38 % were Progesterone Receptor positive, 18% were HER2 positive, 24% were hormone receptor negative
Complications
5% of cycles were cancelled prior to OPU, 8% of cycles resulted in no oocyte or embryo available for freezing. 3% of cycles were reviewed for OHSS symptoms with 2 confirmed cases of OHSS secondary to administration of Zoladex &lt;24hrs following OPU.

Limitations, reasons for caution
This is a retrospective cohort study in a single academic centre.
Our current study duration is too short to permit determination of recurrence rates of breast cancer in the letrozole treated cohort.

Wider implications of the findings
The impact of short, transient elevation of circulating estradiol during superovulation is uncertain, however it is prudent to try to minimise exposure of ER positive breast cancers to estrogen. Alternative strategies for limiting this phenomenon should be explored, more evidence is needed on oncological and fertility outcomes in this population.

Trial registration number
N/A