GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer

the Anglo Celtic Group OPTION trial

R. C. F. Leonard (Lead / Corresponding author), D. J. A. Adamson, G. Bertelli, J. Mansi, A. Yellowlees, J. Dunlop, G. A. Thomas, R. E. Coleman, R. A. Anderson, for the Anglo Celtic Collaborative Oncology Group and National Cancer Research Institute trialists

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Abstract

Background: Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women’s health. The OPTION trial tested whether administration of a gonadotropin hormone releasing hormone (GnRH) agonist during chemotherapy for early breast cancer reduced the risk of POI.

Patients and Methods: This was a prospective, randomized, parallel group study of the GnRH agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone (FSH) concentrations to give an additional analysis as rate of POI.

Results: A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% vs 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% vs 34.8% in the control group (P = 0.048). FSH concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001 respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone (AMH) showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups.

Conclusion: This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer-term prevention of estrogen deficiency-related outcomes needs to be determined.

Trial registration: EudraCT 2004-000133-11

Original languageEnglish
Pages (from-to)1811-1816
Number of pages6
JournalAnnals of Oncology
Volume28
Issue number8
Early online date2 May 2017
DOIs
Publication statusPublished - Aug 2017

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Goserelin
Gonadotropin-Releasing Hormone
Hormones
Breast Neoplasms
Drug Therapy
Amenorrhea
Follicle Stimulating Hormone
Control Groups
Fertility
Women's Health
Random Allocation
Estrogens

Keywords

  • breast cancer
  • ovary
  • GnRH
  • GnRH analogue
  • chemoprotection

Cite this

Leonard, R. C. F., Adamson, D. J. A., Bertelli, G., Mansi, J., Yellowlees, A., Dunlop, J., ... for the Anglo Celtic Collaborative Oncology Group and National Cancer Research Institute trialists (2017). GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial. Annals of Oncology, 28(8), 1811-1816. https://doi.org/10.1093/annonc/mdx184
Leonard, R. C. F. ; Adamson, D. J. A. ; Bertelli, G. ; Mansi, J. ; Yellowlees, A. ; Dunlop, J. ; Thomas, G. A. ; Coleman, R. E. ; Anderson, R. A. ; for the Anglo Celtic Collaborative Oncology Group and National Cancer Research Institute trialists. / GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer : the Anglo Celtic Group OPTION trial. In: Annals of Oncology. 2017 ; Vol. 28, No. 8. pp. 1811-1816.
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abstract = "Background: Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women’s health. The OPTION trial tested whether administration of a gonadotropin hormone releasing hormone (GnRH) agonist during chemotherapy for early breast cancer reduced the risk of POI.Patients and Methods: This was a prospective, randomized, parallel group study of the GnRH agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone (FSH) concentrations to give an additional analysis as rate of POI.Results: A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22{\%} vs 38{\%} in the control group (P = 0.015) and the prevalence of POI to 18.5{\%} vs 34.8{\%} in the control group (P = 0.048). FSH concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001 respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-M{\"u}llerian hormone (AMH) showed a marked fall in both groups during treatment to median values of 5{\%} of pretreatment levels in the control group and 7{\%} in the goserelin group, which were not significantly different between groups.Conclusion: This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer-term prevention of estrogen deficiency-related outcomes needs to be determined.Trial registration: EudraCT 2004-000133-11",
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Leonard, RCF, Adamson, DJA, Bertelli, G, Mansi, J, Yellowlees, A, Dunlop, J, Thomas, GA, Coleman, RE, Anderson, RA & for the Anglo Celtic Collaborative Oncology Group and National Cancer Research Institute trialists 2017, 'GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial', Annals of Oncology, vol. 28, no. 8, pp. 1811-1816. https://doi.org/10.1093/annonc/mdx184

GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer : the Anglo Celtic Group OPTION trial. / Leonard, R. C. F. (Lead / Corresponding author); Adamson, D. J. A.; Bertelli, G.; Mansi, J.; Yellowlees, A.; Dunlop, J.; Thomas, G. A.; Coleman, R. E.; Anderson, R. A.; for the Anglo Celtic Collaborative Oncology Group and National Cancer Research Institute trialists.

In: Annals of Oncology, Vol. 28, No. 8, 08.2017, p. 1811-1816.

Research output: Contribution to journalArticle

TY - JOUR

T1 - GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer

T2 - the Anglo Celtic Group OPTION trial

AU - Leonard, R. C. F.

AU - Adamson, D. J. A.

AU - Bertelli, G.

AU - Mansi, J.

AU - Yellowlees, A.

AU - Dunlop, J.

AU - Thomas, G. A.

AU - Coleman, R. E.

AU - Anderson, R. A.

AU - for the Anglo Celtic Collaborative Oncology Group and National Cancer Research Institute trialists

N1 - This study was funded by Cancer Research UK (CRUK/04/004).

PY - 2017/8

Y1 - 2017/8

N2 - Background: Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women’s health. The OPTION trial tested whether administration of a gonadotropin hormone releasing hormone (GnRH) agonist during chemotherapy for early breast cancer reduced the risk of POI.Patients and Methods: This was a prospective, randomized, parallel group study of the GnRH agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone (FSH) concentrations to give an additional analysis as rate of POI.Results: A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% vs 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% vs 34.8% in the control group (P = 0.048). FSH concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001 respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone (AMH) showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups.Conclusion: This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer-term prevention of estrogen deficiency-related outcomes needs to be determined.Trial registration: EudraCT 2004-000133-11

AB - Background: Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women’s health. The OPTION trial tested whether administration of a gonadotropin hormone releasing hormone (GnRH) agonist during chemotherapy for early breast cancer reduced the risk of POI.Patients and Methods: This was a prospective, randomized, parallel group study of the GnRH agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone (FSH) concentrations to give an additional analysis as rate of POI.Results: A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% vs 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% vs 34.8% in the control group (P = 0.048). FSH concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001 respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone (AMH) showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups.Conclusion: This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer-term prevention of estrogen deficiency-related outcomes needs to be determined.Trial registration: EudraCT 2004-000133-11

KW - breast cancer

KW - ovary

KW - GnRH

KW - GnRH analogue

KW - chemoprotection

U2 - 10.1093/annonc/mdx184

DO - 10.1093/annonc/mdx184

M3 - Article

VL - 28

SP - 1811

EP - 1816

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 8

ER -