GnRHa for Ovarian Protection and the Association between AMH and Ovarian Function during Adjuvant Chemotherapy for Breast Cancer

1094 Background: The OPTION trial in premenopausal women tested the ovarian protection effect of goserelin (G) given randomly before and during adjuvant chemotherapy for breast cancer. Methods: Using standard chemotherapy, women were randomised in 2 strata, under 40 yrs and over 40 yrs at diagnosis. 227 patients were recruited by end December 2009. 173 met the criteria for 1 year follow-up for this analysis; 140 patients of these had provided adequate data on menstrual bleeding; 87 patients were aged under 40 and 53 patients were aged over 40 at the time of chemotherapy. Cessation of menstruation during chemotherapy was defined as at least two consecutive cycles with no menstrual bleeding since the previous cycle and no return of menstrual bleeding prior to the final cycle of chemotherapy. Of those patients who had ceased periods during chemotherapy, those with no further menstrual bleeding at 12 months follow up were deemed to be menopausal. Patients were randomised to receive G or no G at start of chemotherapy. Primary endpoint was recovery of menses at 12 months from start of chemotherapy. AMH was measured in 117 women pre-treatment, and at 1 year after starting chemotherapy. Results: There were no differences in pretreatment AMH between control and goserelin-treated groups, thus further analyses were performed on all women grouped together. AMH was lower following chemotherapy (0.40±0.65 vs 1.38±1.82ng/ml; mean±SD; P<0.001)). Pre-treatment AMH was a significant predictor of post-treatment amenorrhoea (P=0.001). By multivariate logistic regression analysis with age and AMH, age remained significant (P=0.003) whereas AMH did not (P=0.07). Grouping pre-treatment and post-chemo AMH into quartiles showed that AMH became undetectable in 94% of women with lowest pre-treatment AMH vs 46.2% of women with the highest pretreatment AMH. We have previously demonstrated in a small cohort that pretreatment AMH can predict long-term (5 year) ovarian activity in women with breast cancer. Conclusions: The present data confirm the value of pretreatment AMH in assessing the likelihood of ongoing ovarian activity after chemotherapy for early breast cancer.

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Randomized Trial Using Gonadotropin-Releasing Hormone Agonist Triptorelin for the Preservation of Ovarian Function During (Neo)Adjuvant Chemotherapy for Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2011.34.6890 ◽

2012 ◽

Vol 30 (5) ◽

pp. 533-538 ◽

Cited By ~ 146

Author(s):

Pamela N. Munster ◽

Amy P. Moore ◽

Roohi Ismail-Khan ◽

Charles E. Cox ◽

Mensura Lacevic ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Adjuvant Chemotherapy ◽

Randomized Trial ◽

Ovarian Function ◽

Estrogen Receptor Status ◽

Gonadotropin Releasing Hormone ◽

Control Group ◽

Releasing Hormone ◽

Neo Adjuvant Chemotherapy

Purpose Chemotherapy-induced amenorrhea is a serious concern for women undergoing cancer therapy. This prospective randomized trial evaluated the use of gonadotropin-releasing hormone (GnRH) analog triptorelin to preserve ovarian function in women treated with chemotherapy for early-stage breast cancer. Patients and Methods Premenopausal women age 44 years or younger were randomly assigned to receive either triptorelin or no triptorelin during (neo)adjuvant chemotherapy and were further stratified by age (< 35, 35 to 39, > 39 years), estrogen receptor status, and chemotherapy regimen. Objectives included the resumption of menses and serial monitoring of follicle-stimulating hormone (FSH) and inhibin A and B levels. Results Targeted for 124 patients with a planned 5-year follow-up, the trial was stopped for futility after 49 patients were enrolled (median age, 39 years; range, 21 to 43 years); 47 patients were treated according to assigned groups with four cycles of adriamycin plus cyclophosphamide alone or followed by four cycles of paclitaxel or six cycles of fluorouracil, epirubicin, and cyclophosphamide. Menstruation resumed in 19 (90%) of 21 patients in the control group and in 23 (88%) of 26 in the triptorelin group (P= .36). Menses returned after a median of 5.8 months (range, 1 to 19 months) after completion of chemotherapy in the triptorelin versus 5.0 months (range, 0 to 28 months) in the control arm (P= .58). Two patients (age 26 and 35 years at random assignment) in the control group had spontaneous pregnancies with term deliveries. FSH and inhibin B levels correlated with menstrual status. Conclusion When stratified for age, estrogen receptor status, and treatment regimen, amenorrhea rates on triptorelin were comparable to those seen in the control group.

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