Abstract
About 5%–6% of all breast cancer develops in young women (≤40 years old). Some of them had not yet had a child while diagnosed with malignancy. Fertility preservation before systemic therapy, which is used in most patients, is essential for them. There are a few options to preserve fertility: assisted reproductive technology (ART) (cryopreservation of embryos, oocytes, or ovarian tissue) and gonadotropin releasing hormone (GnRH) analogs. 1 From many years we have dealt with these problems at Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland. 2
Jach et al. 3 have recently published the “Recommendations of the Fertility Preservation Working Group in Oncological, Hematological and Other Patients Treated with Gonadotoxic Therapies ‘ONCOFERTILITY’ (GROF) of the Polish Society of Oncological Gynecology.” This document highlights the importance of the topic and proposes the recommendations. The authors state that GnRH analogs can be used during chemotherapy only in triple-negative breast cancer patients (who represent 10%–20% of all breast cancer). We notice a wider group of young breast cancer patients who can benefit from GnRH analogs for preserving ovarian function and fertility. In a meta-analysis of 12 randomized controlled trials, published in 2015, the risk of premature ovarian failure was significantly reduced in patients treated with concurrent GnRH analogs comparing with women treated only with chemotherapy [odds ratio (OR): 0.36; 95% confidence interval (CI): 0.23–0.57; p < 0.001]. 4 The chance for pregnancy in the future was higher in patients using GnRH analogs during chemotherapy (data from five studies: 33 vs. 19 women; OR: 1.83; 95% CI: 1.02–3.28; p = 0.041).
Pregnancy in women who have undergone treatment for breast cancer does not increase the risk of either recurrence or death, also in case of luminal breast cancer. The aforementioned meta-analysis showed no impact of using temporary ovarian suppression on prognosis (disease free survival [DFS] hazard ratio [HR]: 1.00; 95% CI: 0.49–2.04; p = 0.939). 4 Data from trials analyzing different breast cancer subtypes support this statement (including POEMS, PROMISE-GIM6, and OPTION trials). 5
Finally, according to recently published ESO-ESMO 3rd international consensus guidelines for breast cancer in young women (BCY3) GnRH agonists should be discussed as an option with all interested patients, irrespective of biologic tumor subtype. 1 For some women who are unable to have fertility preservation procedures, access to GRNH agonists will allow an opportunity to preserve fertility.
Jach et al. 3 recommend using GnRH analogs only if the other options to preserve fertility cannot be applied. We propose that fertility preservation procedures can be combined with ovarian suppression. This strategy can increase the chance for fertility and gonadal function preservation. In some patients, there is a chance to become pregnant without ART, and GnRH analogs improve this possibility. This approach can reduce medical procedures and costs.
In conclusion, young cancer patients should be referred to a specialist in fertility preservation as soon as the decision on systemic therapy is made. ART and GnRH analogs should be discussed with all of them.