Context and Objectives: In French-speaking Switzerland, 5% of breast cancers are diagnosed in women under the age of 40 (1)(2). For these patients, whose fertility may be threatened by the gonadotoxicity of chemotherapy (CT), a consultation with a specialist in reproductive medicine is recommended to discuss fertility preservation (FP) options before starting treatment (3). For patients aged 18 to 42, the preferred technique is the cryopreservation of oocytes or embryos. After ovarian stimulation (OS), mature oocytes are retrieved and then vitrified, ready for in vitro fertilization (IVF) (4). Two windows of opportunity exist for this method during treatment: between surgery and the start of adjuvant chemotherapy (AC) or between diagnosis and the start of neoadjuvant chemotherapy (NAC) (5). Thanks to the Random Start protocol with Letrozole, OS can be safely initiated regardless of the phase of the menstrual cycle (6), enabling oncological treatment to begin as soon as possible. The main objective of this study is to determine whether FP delayed the onset of CT in patients of reproductive age diagnosed at Lausanne University Hospital. One of the exploratory objectives was to assess whether complications occurred during the FP protocol and delayed the start of systemic treatment.
Method: This study is an exploratory retrospective analysis of data collected from the medical records of women aged 18 to 40 years who were newly diagnosed with invasive breast cancer at Lausanne University Hospital between March 2020 and 2023. We compared time in days, from diagnosis to the first day of NAC or AC, in a group of women who pursued FP and in a control group, matched for age and tumor type, that did not undergo FP before treatment. Patients who had not signed the general consent form, patients whose PF was performed ex-domo, and patients who did not undergo CT during their treatment, were excluded from the study.
Results: 39 patients aged 18 to 40 were newly diagnosed with breast cancer and underwent FP at Lausanne University Hospital between March 2020 and 2023. Nine patients did not authorize data reuse, and five were excluded. A total of 25 medical records from the PREFEC group and 27 from the control group were analyzed. The mean age was 33.96 years in the PREFEC group and 35.48 years in the control group. In the PREFEC (Preservation Fertility and Cancer) group, 40% underwent NAC and 60% AC, while in the control group, 63% underwent NAC and 37% AC. The most common tumor type in both groups was invasive NST, with stages II and III being the most frequent. In the PREFEC group, the median time between diagnosis and CT was 48 days (IQR 29), compared to 28 days (IQR 20) in the control group, p = 0.0027. The median time from diagnosis to NAC was 33 days (IQR 14) in the PREFEC group and 23 days (IQR 11) in the control group, the median time from diagnosis to AC was 59 days (IQR 23) in the PREFEC group and 53 days (IQR 37) in the control group; respectively p = 0.0021 and p = 0.0057. In the FP group, 4 patients experienced minor complications (1 minor Ovarian Hyperstimulation Syndrome, 1 minor bleeding after retrieval, 1 urinary infection following retrieval, and 1 failure of ovulation induction). None of these delayed the initiation of CT.
Conclusion: CT was initiated median 10 days later in the neoadjuvant setting, and median 6 days later in the adjuvant setting, in patients who pursued FP before the beginning of their treatment. The delays were consistent with those reported in similar studies, although slightly longer than recommended timelines. While minor complications related to FP were observed, they did not notably impact the timing of chemotherapy initiation. The analysis of our data should be taken further by performing a multivariable regression analysis to examine the treatment initiation delay between the two groups, adjusting for age, chemotherapy type, and disease stage. Further prospective research conducted on a larger sample size and over a longer period are needed to support these results.