AMH is a promising biomarker of treatment-induced gonadal damage. The impact of carrying a deleterious germline BRCA mutation, adding a taxane to anthracycline-based CT and using adjuvant ET on gonadal function following CT remains unclear. We assessed the influence of these 3 factors on AMH levels before and after adjuvant CT in EBC patients.
This monocentric retrospective study included consecutive EBC patients aged ≤40 years treated with adjuvant FEC CT between 2008 and 2016, known germline BRCA status and available frozen plasma samples before and after CT. AMH levels (ng/mL) were assessed before starting CT, 1 year and over 3 year after diagnosis.
148 patients were included. 35 (24%) patients harbored a deleterious germline BRCA mutation, 127 (86%) received a taxane following FEC CT and 90 (61%) had adjuvant ET after CT. Overall median age was 35 (range 22-40). In the whole cohort, median AMH levels dropped after adjuvant CT (from 1.69 to 0.06, p < 0.0001) and slightly recovered after 3 years (0.17, p < 0.0001). No difference in baseline (1.94 vs 1.66, p = 0.53), 1-year (0.09 vs 0.06, p = 0.39) or 3-year (0.25 vs 0.16, p = 0.43) AMH levels was observed between patients with or without a BRCA mutation. Significant lower AMH levels were observed for patients who received a FEC-taxane regimen as compared to those treated with FEC only CT 1 year after diagnosis (0.04 vs 0.22, p = 0.0006), with no difference at 3 years (0.18 vs 0.06, p = 0.47). Patients treated with adjuvant ET had slightly higher AMH levels than those who did not receive ET 1 year after diagnosis (0.12 vs 0.02, p = 0.008) with no difference at 3 years (0.11 vs 0.20, p = 0.22).
Use of adjuvant CT is associated with a significant and durable alteration in ovarian reserve measured by AMH levels. Addition of taxanes to FEC increased CT-induced gonadotoxicity immediately after CT exposure but not at longer follow-up. Carrying a germline BRCA mutation and using adjuvant ET following CT were not associated with additional negative impact on patients’ ovarian reserve after treatment.
Clinical trial identification
Legal entity responsible for the study
Centre Henri Becquerel, Rouen, France.
Has not received any funding.
All authors have declared no conflicts of interest.