Safety of ovarian stimulation with letrozole and gonadotropins in breast cancer patients undergoing embryo or oocyte cryopreservation: a prospective controlled study

Abstract

We have previously developed a protocol utilizing letrozole to minimize the rise of estradiol levels during ovarian stimulation (COH) in women with breast cancer. The objective of this study was to determine whether COH increase breast cancer recurrence. Prospective nonrandomized trial. Of the 215 women with breast cancer who were evaluated for fertility preservation, 79 elected to undergo COH with letrozole and gonadotropins for embryo or oocyte cryopreservation. The 136 patients who declined due to concerns about the safety, cost, and delay of chemotherapy served as controls. Stage 4 disease was excluded. Patients and/or their oncologists were contacted for recurrence information. To adjust for prognostic differences between the two groups, 10-year survival rates were calculated using Adjuvant Online. Groups were similar in terms of age at diagnosis (36.1 ± 3.8 vs. 35.6 ± 4.7, P=0.4), breast cancer prognostic parameters (tumor size, grade, number of positive lymph nodes, estrogen receptor status, her2-neu overexpression and vascular space invasion), and chemotherapy regimens. There was no difference in the projected 10 year relapse, breast cancer specific mortality or overall mortality at enrollment. There was a trend for higher estrogen receptor positivity in the COH group (P=0.08). Time between surgery and chemotherapy was longer for IVF patients (45.08 ± 31.64 vs. 33.46 ± 27.3 days, P<0.01). Peak E2 levels ranged from 58.4 to 1166 (mean 405.94 ± 256.64 pg/mL in COH patients. The median length of follow up after chemotherapy was 1.66 (range 0.29–10.28) years in the COH and 2.67 (range 0.29–9.5) years in the control group. There were 3 recurrences of contralateral breast cancers (2 distant, 1 locoregional) in the COH, and 11 in the control group (9 distant, 1 locoregional, 1 contralateral breast) (P=0.26) (Table). There was no significant difference in survival between the groups (Kaplan-Meier method, P=0.31, hazard ratio 0.53, 95% CI 0.17 to 1.8). Breast cancer recurrence or the incidence of invasive carcinoma in the contralateral breast does not appear to be increased after COH using letrozole and FSH for fertility preservation.Tabled 1Table.Letrozole group (n = 79)Control group (n = 141)Length of stimulation (day)9.87 ± 2.28NATotal gonodatropin dose (mlU/ml)1698.62 ± 818.76NANumber of oocytes retrieved10.3 ± 7.75NANumber of embryos or oocytes cryopreserved5.97 ± 4.97NALength of follow up (years) Mean2.18 ± 1.83.08 ± 2.17 Median1.662.67 Range0.29 – 10.280.29 – 9.5Patients with follow up information (%)79 (100)102 (75)Recurrence (%)3 (3.8)11 (8.1) Locoregional11 Distant29 Carcinoma in contralateral breast01Pregnancy (ongoing or delivery) Spontaneous13 After frozen embryo transfer8NA Open table in a new tab