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

R. A. Anderson (Lead / Corresponding author), J. Mansi, R. E. Coleman, D. J. A. Adamson, R. C. F. Leonard

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    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.

    Original languageEnglish
    Pages (from-to)58-64
    Number of pages7
    JournalEuropean Journal of Cancer
    Volume87
    Early online date5 Nov 2017
    DOIs
    Publication statusPublished - Dec 2017

    Fingerprint

    Hormones
    Breast Neoplasms
    Drug Therapy
    Goserelin
    Area Under Curve
    Follicle Stimulating Hormone
    Sensitivity and Specificity
    Amenorrhea
    Tamoxifen
    Gonadotropin-Releasing Hormone
    ROC Curve
    Limit of Detection
    Odds Ratio

    Keywords

    • Breast cancer
    • Hormone sensitive
    • Menopause
    • Ovarian function

    Cite this

    Anderson, R. A. ; Mansi, J. ; Coleman, R. E. ; Adamson, D. J. A. ; Leonard, R. C. F. / The utility of anti-Müllerian hormone in the diagnosis and prediction of loss of ovarian function following chemotherapy for early breast cancer. In: European Journal of Cancer. 2017 ; Vol. 87. pp. 58-64.
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    title = "The utility of anti-M{\"u}llerian 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-M{\"u}llerian 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",
    author = "Anderson, {R. A.} and J. Mansi and Coleman, {R. E.} and Adamson, {D. J. A.} and Leonard, {R. C. F.}",
    note = "The OPTION trial was funded by Cancer Research UK (ref C4831/A4181). We are grateful to Roche Diagnostics for the provision of hormone assay materials.This work was undertaken in the MRC Centre for Reproductive Health which is funded by the MRC Centre grant MR/N022556/1",
    year = "2017",
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    The utility of anti-Müllerian hormone in the diagnosis and prediction of loss of ovarian function following chemotherapy for early breast cancer. / Anderson, R. A. (Lead / Corresponding author); Mansi, J.; Coleman, R. E.; Adamson, D. J. A.; Leonard, R. C. F.

    In: European Journal of Cancer, Vol. 87, 12.2017, p. 58-64.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The utility of anti-Müllerian hormone in the diagnosis and prediction of loss of ovarian function following chemotherapy for early breast cancer

    AU - Anderson, R. A.

    AU - Mansi, J.

    AU - Coleman, R. E.

    AU - Adamson, D. J. A.

    AU - Leonard, R. C. F.

    N1 - The OPTION trial was funded by Cancer Research UK (ref C4831/A4181). We are grateful to Roche Diagnostics for the provision of hormone assay materials.This work was undertaken in the MRC Centre for Reproductive Health which is funded by the MRC Centre grant MR/N022556/1

    PY - 2017/12

    Y1 - 2017/12

    N2 - 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.

    AB - 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.

    KW - Breast cancer

    KW - Hormone sensitive

    KW - Menopause

    KW - Ovarian function

    U2 - 10.1016/j.ejca.2017.10.001

    DO - 10.1016/j.ejca.2017.10.001

    M3 - Article

    VL - 87

    SP - 58

    EP - 64

    JO - European Journal of Cancer

    JF - European Journal of Cancer

    SN - 0959-8049

    ER -