Abstract
AimAnti-Müllerian hormone (AMH) shows promise as a biomarker of the ovarian reserve but current assays are insufficiently sensitive to allow assessment of this post-chemotherapy in most women. We have assessed a new highly sensitive AMH assay (Ansh picoAMH) in the evaluation of ovarian activity in women with very low ovarian reserve after chemotherapy. MethodsA prospective cohort and an independent validation cohort of premenopausal women with early breast cancer (eBC) were recruited at the time of diagnosis (combined n=98), and ovarian reserve markers 2–5years later following chemotherapy were assessed in relation to menstrual activity. ResultsThe picoAMH assay had a limit of detection of 7.5pg/ml. AMH clearly distinguished women with ongoing menses from those with amenorrhoea at 2years after diagnosis (mean 522±169 versus 8.9±1.3pg/ml, P<0.0001) with high predictive value for continuing menses or amenorrhoea for the subsequent 3years. AMH was detectable in more women than using a previous assay (P=0.004). Other markers of the ovarian reserve (follicle-stimulating hormone (FSH), inhibin B) were also of discriminatory value but to lesser extents. This finding was validated in a second, independent cohort of women treated for eBC. ConclusionThe 10-fold increased assay sensitivity showed very clear distinction between groups based on ovarian activity with excellent prediction of future menses or amenorrhoea. This will improve assessment of post-chemotherapy ovarian function in women and may aid treatment decisions.
Highlights
Adjuvant chemotherapy is a mainstay of treatment of early breast cancer as it results in an improvement in both disease-free and overall survival rate [1]
Amongst the 56 women recruited to the initial cohort, 39 in the chemotherapy group and 14 in the non-chemotherapy group remained in the study at 2 years, the key time point for analysis; the remaining three women had either withdrawn from the study because of disease recurrence or had discontinued follow-up after hysterectomy and oophorectomy
We examined a panel of reproductive hormones of ovarian function including Anti-Mullerian hormone (AMH), inhibin B, follicle-stimulating hormone (FSH), and estradiol in early breast cancer (eBC) survivors, and used a highly sensitive AMH assay to evaluate the ovarian reserve in this group of patients
Summary
Adjuvant chemotherapy is a mainstay of treatment of early breast cancer (eBC) as it results in an improvement in both disease-free and overall survival rate [1]. Breast cancer survivors in their reproductive age are confronted with the long-term consequences of exposure to these treatments, and quality of life issues including fertility are becoming more important. Chemotherapeutic agents can have a profound impact on ovarian function. They cause a depletion of the follicle pool in a drug- and dose-dependent manner [2]. Recovery of menses in some women after chemotherapy illustrates the limitation of amenorrhoea as a marker of complete loss of the ovarian reserve; the resumption of menses may be only brief indicating preservation of only a very low ovarian reserve
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