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

Eur J Cancer. 2017 Dec:87:58-64. doi: 10.1016/j.ejca.2017.10.001. Epub 2017 Nov 5.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Anti-Mullerian Hormone / blood*
  • Antineoplastic Agents / adverse effects*
  • Area Under Curve
  • Biomarkers / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Odds Ratio
  • Ovary / drug effects*
  • Ovary / metabolism
  • Ovary / physiopathology
  • Predictive Value of Tests
  • Primary Ovarian Insufficiency / blood
  • Primary Ovarian Insufficiency / chemically induced*
  • Primary Ovarian Insufficiency / diagnosis
  • ROC Curve
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Anti-Mullerian Hormone