Prediction of postchemotherapy ovarian function using markers of ovarian reserve.

BACKGROUND Reproductive-aged women frequently receive both chemotherapy and endocrine therapy as part of their treatment regimen for early stage hormone receptor-positive breast cancer. Chemotherapy results in transient or permanent ovarian failure in the majority of women. The difficulty in determining which patients will recover ovarian function has implications for adjuvant endocrine therapy decision making. We hypothesized that pretreatment serum anti-Müllerian hormone (AMH) and inhibin B concentrations would predict for ovarian function following chemotherapy. METHODS Pre- and perimenopausal women aged 25-50 years with newly diagnosed breast cancer were enrolled. Subjects underwent phlebotomy for assessment of serum AMH, inhibin B, follicle-stimulating hormone, and estradiol prior to chemotherapy and 1 month and 1 year following completion of treatment. Associations among hormone concentrations, clinical factors, and biochemically assessed ovarian function were assessed. RESULTS Twenty-seven subjects were evaluable for the primary endpoint. Median age was 41. Twenty subjects (74.1%) experienced recovery of ovarian function within 18 months. Of the 26 evaluable subjects assessed prior to chemotherapy, 19 (73.1%) had detectable serum concentrations of AMH. The positive predictive value of a detectable baseline serum AMH concentration for recovery of ovarian function was 94.7%, and the negative predictive value was 85.7%. On univariate analysis, younger age and detectable serum AMH concentration at chemotherapy initiation were predictive of increased likelihood of recovery of ovarian function. CONCLUSION Prechemotherapy assessment of serum AMH may be useful for predicting postchemotherapy ovarian function. This finding has implications for decision making about adjuvant endocrine therapy in premenopausal women treated with chemotherapy.

[1]  P. Ganz,et al.  Life after breast cancer: understanding women's health-related quality of life and sexual functioning. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  Nanette Santoro,et al.  Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status. , 2003, The Journal of clinical endocrinology and metabolism.

[3]  P. Patrizio,et al.  American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  Gwyn McClelland Survivors , 1891, The Hospital.

[5]  R. Fanchin,et al.  Serum anti-Müllerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3. , 2003, Human reproduction.

[6]  A. DeMichele,et al.  Antimullerian hormone and inhibin B are hormone measures of ovarian function in late reproductive‐aged breast cancer survivors , 2010, Cancer.

[7]  J. Habbema,et al.  Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study. , 2005, Fertility and sterility.

[8]  A. DeMichele,et al.  Antral follicle count provides additive information to hormone measures for determining ovarian function in breast cancer survivors. , 2009, Fertility and sterility.

[9]  K. Blackwell,et al.  A Pilot Study of Predictive Markers of Chemotherapy-Related Amenorrhea Among Premenopausal Women with Early Stage Breast Cancer , 2008, Cancer investigation.

[10]  M. Ellis,et al.  Adjuvant Aromatase Inhibitors for Early Breast Cancer After Chemotherapy-Induced Amenorrhoea: Caution and Suggested Guidelines , 2007 .

[11]  S. Singletary,et al.  Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  C. Simón,et al.  Evaluation of the ovarian reserve in young low responders with normal basal levels of follicle-stimulating hormone using three-dimensional ultrasonography. , 1998, Fertility and sterility.

[13]  W. Rocca,et al.  Premature menopause or early menopause: long-term health consequences. , 2010, Maturitas.

[14]  S. Crawford,et al.  Assessing menstrual cycles with urinary hormone assays. , 2003, American journal of physiology. Endocrinology and metabolism.

[15]  Richard A. Anderson,et al.  Pretreatment serum anti-müllerian hormone predicts long-term ovarian function and bone mass after chemotherapy for early breast cancer. , 2011, The Journal of clinical endocrinology and metabolism.

[16]  P. Goss,et al.  Superiority of gas chromatography/tandem mass spectrometry assay (GC/MS/MS) for estradiol for monitoring of aromatase inhibitor therapy , 2007, Steroids.

[17]  F. Broekmans,et al.  Serum anti-Müllerian hormone levels: a novel measure of ovarian reserve. , 2002, Human reproduction.

[18]  M. Ferin,et al.  Changes in markers of ovarian reserve and endocrine function in young women with breast cancer undergoing adjuvant chemotherapy , 2010, Cancer.

[19]  J. Griggs,et al.  American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  L. Schapira,et al.  Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer. , 2010, Fertility and sterility.

[21]  M. Banerjee,et al.  Predictors of recovery of ovarian function during aromatase inhibitor therapy. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[22]  P. Goodwin,et al.  Risk of menopause during the first year after breast cancer diagnosis. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  C. Hudis,et al.  Inadvertent use of aromatase inhibitors in patients with breast cancer with residual ovarian function: cases and lessons. , 2006, Clinical breast cancer.

[24]  S. Singletary,et al.  Incidence and time course of bleeding after long‐term amenorrhea after breast cancer treatment , 2010, Cancer.