title: Pretreatment anti-Müllerian hormone predicts for loss of ovarian function after chemotherapy for early breast cancer.
abstract: OBJECTIVE
  Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea.
  
  
  METHODS
  Women (n=59, mean age 42.6 years [(range 23.3-52.5]) with eBC were recruited before any treatment. Pretreatment ovarian reserve markers (anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], inhibin B) were analysed in relation to ovarian status at 2 years.
  
  
  RESULTS
  Pretreatment AMH was significantly lower in women with amenorrhoea at 2 years (4.0 ± 0.9 pmol/L versus 17.2 ± 2.5, P<0.0001), but FSH and inhibin B did not differ between groups. By logistic regression, pretreatment AMH, but not age, FSH or inhibin B, was an independent predictor of ovarian status at 2 years (P=0.005; odds ratio 0.013). We combined these data with a similar cohort (combined n=75); receiver-operator characteristic analysis for AMH gave area under curve (AUC) of 0.90 (95% confidence interval (CI) 0.82-0.97)). A cross-validated classification tree analysis resulted in a binary classification schema with sensitivity 98.2% and specificity 80.0% for correct classification of amenorrhoea.
  
  
  CONCLUSIONS
  Pretreatment AMH is a useful predictor of long term post chemotherapy loss of ovarian function in women with eBC, adding significantly to the only previously established individualising predictor, i.e. age. AMH measurement may assist decision-making regarding treatment options and fertility preservation procedures.
authors: MRC Centre for Reproductive Health, University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. Electronic address: richard.anderson@ed.ac.uk.
authors: Richard A
authors: RA
authors: Anderson
authors: Mikkel
authors: M
authors: Rosendahl
authors: Thomas W
authors: TW
authors: Kelsey
authors: David A
authors: DA
authors: Cameron
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D054304:Anti-Mullerian Hormone / Q000097:blood*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003718:Denmark; D015536:Down-Regulation; D055088:Early Detection of Cancer; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000097:blood; D006801:Humans; D007265:Inhibins / Q000097:blood; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D012606:Scotland; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D043373:Follicle Stimulating Hormone, Human; C422364:inhibin B; D007265:Inhibins; D054304:Anti-Mullerian Hormone
keywords: AMH; Amenorrhoea; Breast cancer; Chemotherapy; Fertility; Ovarian reserve
references: Cancer. 2010 May 1;116(9):2099-105
references: 20187091
references: Hum Reprod. 2006 Oct;21(10):2583-92
references: 16820385
references: N Engl J Med. 2010 Jun 3;362(22):2053-65
references: 20519679
references: Fertil Steril. 2010 Feb;93(3):855-64
references: 19046583
references: PLoS One. 2010 Jan 27;5(1):e8772
references: 20111701
references: J Clin Endocrinol Metab. 2012 Jun;97(6):2059-67
references: 22472563
references: Reprod Biomed Online. 2010 Feb;20(2):280-5
references: 20113967
references: Ann Clin Biochem. 2011 Jul;48(Pt 4):370-3
references: 21628625
references: Best Pract Res Clin Obstet Gynaecol. 2009 Feb;23(1):7-23
references: 19046657
references: J Clin Endocrinol Metab. 2011 May;96(5):1336-43
references: 21325458
references: BMC Cancer. 2008 Feb 21;8:56
references: 18291033
references: J Clin Oncol. 1996 May;14(5):1718-29
references: 8622093
references: Fertil Steril. 2005 Apr;83(4):979-87
references: 15820810
references: Fertil Steril. 2012 Jan;97(1):134-40.e1
references: 22137491
references: Fertil Steril. 2010 Jun;94(1):156-66
references: 19342041
references: Hum Reprod. 2008 Mar;23(3):674-8
references: 18216040
references: J Clin Oncol. 1997 Feb;15(2):547-56
references: 9053476
references: Hum Reprod. 2003 Nov;18(11):2368-74
references: 14585889
references: Hum Reprod. 2009 Apr;24(4):982-90
references: 19153092
references: Hum Reprod Update. 2012 Sep-Oct;18(5):525-35
references: 22647504
references: Lancet. 2005 May 14-20;365(9472):1687-717
references: 15894097
references: Hum Reprod Update. 2006 Nov-Dec;12(6):685-718
references: 16891297
references: Hum Reprod. 1992 Nov;7(10):1342-6
references: 1291557
references: Maturitas. 2012 Jan;71(1):28-33
references: 22119275
references: Eur J Cancer. 2009 Dec;45(18):3198-204
references: 19818599
references: Cancer. 2012 Mar 15;118(6):1710-7
references: 21887678
references: J Clin Oncol. 2006 Mar 1;24(7):1045-51
references: 16476708
references: Reprod Biomed Online. 2012 Dec;25(6):612-9
references: 23069740
references: Clin Obstet Gynecol. 2010 Dec;53(4):727-39
references: 21048440
references: J Clin Endocrinol Metab. 2012 May;97(5):1673-80
references: 22378815
references: PLoS One. 2011;6(7):e22024
references: 21789206
references: Cancer Invest. 2008 Apr-May;26(3):286-95
references: 18317970
references: Hum Reprod. 2004 Dec;19(12):2738-41
references: 15459174
references: J Clin Oncol. 2006 Jun 20;24(18):2917-31
references: 16651642
references: Cancer. 2010 Feb 1;116(3):592-9
references: 19918920
references: Am J Obstet Gynecol. 1992 Mar;166(3):788-93
references: 1550144
references: Br J Cancer. 2007 Jun 18;96(12):1808-16
references: 17533402