The utility of anti-Müllerian hormone in the diagnosis and prediction of loss of ovarian function following chemotherapy for early breast cancer

Abstract

Aim: Chemotherapy results in permanent loss of ovarian function in some premenopausal women. Accurate identification in women with hormone-sensitive early breast cancer (eBC) would allow optimisation of subsequent endocrine treatment. We sought to assess whether analysis of anti-Müllerian hormone (AMH) using a sensitive automated assay could identify women who would not regain ovarian function after chemotherapy.

Methods: Data from women in the Ovarian Protection Trial in Premenopausal Breast Cancer Patients (OPTION) trial of goserelin (a gonadotrophin-releasing hormone (GnRH) analogue) for ovarian protection were analysed. Women were assessed for premature ovarian insufficiency (POI: amenorrhoea with elevated follicle-stimulating hormone (FSH)) at 24 months after diagnosis. The accuracy of AMH for the diagnosis of POI and its prediction from measurement at the end of chemotherapy was calculated.

Results: AMH below the level of detection showed good diagnostic accuracy for POI at 24 months (n = 73) with receiver operating characteristic (ROC) area under the curve of 0.86, sensitivity 1.0 and specificity 0.73 at the assay limit of detection. In women aged >40 at diagnosis who did not receive goserelin, AMH measured at end of chemotherapy also gave good prediction of POI at 24 months (area under the curve (AUC) 0.89 95% CI 0.75-1.0, n = 32), with sensitivity 0.91, specificity 0.82, diagnostic odds ratio (DOR) 42.8. FSH gave slightly lower AUC, and specificity was low at 0.55. Age but not tamoxifen impacted on AMH levels.

Conclusion: Using this sensitive AMH assay, the finding of an undetectable AMH level in women aged >40 at the end of chemotherapy for eBC gave a good prediction that ovarian function would not return. This may allow alterations in post-chemotherapy endocrine management.

Keywords: Breast cancer; Hormone sensitive; Menopause; Ovarian function.

Fig. 1

Serum oestradiol (A), FSH (B) and AMH (C) at pre-treatment baseline, end of treatment (EOT) and at 12 and 24 months after diagnosis, by POI at 24 months. Data from all women from the OPTION trial. Red, women without POI; blue: women with POI (amenorrhoea plus FSH >25IL/L at 24 months). N = 96 and 28 respectively; median ±95% confidence intervals.

Fig. 2

Serum oestradiol (A), FSH (B) and AMH (C) at end of treatment (EOT) and at 12 and 24 months after diagnosis in women aged ≤40 (open bars) versus >40 years (filled bars); n = 62 and 81, median ± 95% confidence intervals.

Fig. 3

ROC curve analysis of AMH (red) and FSH (blue) at 24 months for (A) analysis of amenorrhoea versus ongoing menses (n = 22 and 51 respectively); (B) for diagnosis of POI versus not POI (n = 14 and 59 respectively). Data from all women in OPTION included.

Fig. 4

ROC curve analysis of (A) AMH (red) and FSH (blue) at end of treatment for prediction of POI versus not POI at 24 months (n = 23 and 45 respectively) for all women in the OPTION control group. (B) AMH (red) and FSH (blue) serum concentrations at end of treatment for prediction of POI versus not POI at 24 months for women aged >40 years in the control group in OPTION (n = 21 and 11 respectively). (C) Oestradiol concentrations at 12 and 24 months in women with undetectable AMH (blue) and detectable AMH (red) at the end of chemotherapy.