Circulating anti-Müllerian hormone and breast cancer risk: A study in ten prospective cohorts

Wenzhen Ge; Tess V Clendenen; Yelena Afanasyeva; Karen L Koenig; Claudia Agnoli; Louise A Brinton; Joanne F Dorgan; A Heather Eliassen; Roni T Falk; Göran Hallmans; Susan E Hankinson; Judith Hoffman-Bolton; Timothy J Key; Vittorio Krogh; Hazel B Nichols; Dale P Sandler; Minouk J Schoemaker; Patrick M Sluss; Malin Sund; Anthony J Swerdlow; Kala Visvanathan; Mengling Liu; Anne Zeleniuch-Jacquotte

doi:10.1002/ijc.31249

Circulating anti-Müllerian hormone and breast cancer risk: A study in ten prospective cohorts

Int J Cancer. 2018 Jun 1;142(11):2215-2226. doi: 10.1002/ijc.31249. Epub 2018 Feb 8.

Authors

Wenzhen Ge¹, Tess V Clendenen¹, Yelena Afanasyeva¹, Karen L Koenig¹, Claudia Agnoli², Louise A Brinton³, Joanne F Dorgan⁴, A Heather Eliassen⁵, Roni T Falk³, Göran Hallmans⁶, Susan E Hankinson^{5

7}, Judith Hoffman-Bolton⁸, Timothy J Key⁹, Vittorio Krogh², Hazel B Nichols¹⁰, Dale P Sandler¹¹, Minouk J Schoemaker¹², Patrick M Sluss¹³, Malin Sund¹⁴, Anthony J Swerdlow^{12

15}, Kala Visvanathan^{8

16}, Mengling Liu^{1

17}, Anne Zeleniuch-Jacquotte^{1

17}

Affiliations

¹ Department of Population Health, New York University School of Medicine, New York, NY.
² Epidemiology and Prevention Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
⁴ Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD.
⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, and Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
⁶ Department of Biobank Research, Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
⁷ Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA.
⁸ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
⁹ Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
¹⁰ Department of Epidemiology, University of North Carolina, Chapel Hill, NC.
¹¹ Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC.
¹² Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
¹³ Department of Pathology, Harvard Medical School, Boston, MA.
¹⁴ Department of Surgery, Umeå University Hospital, Umeå, Sweden.
¹⁵ Division of Breast Cancer Research, The Institute of Cancer Research, London, United Kingdom.
¹⁶ Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD.
¹⁷ Perlmutter Cancer Center, New York University School of Medicine, New York, NY.

Abstract

A strong positive association has been observed between circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case-control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme-linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (p_trend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31-1.94). Though the test for interaction was not statistically significant (p_interaction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: OR_Q4-Q1 = 1.96, 95% CI = 1.46-2.64, p_trend <0.0001; ER+/PR-: OR_Q4-Q1 = 0.82, 95% CI = 0.40-1.68, p_trend = 0.51; ER-/PR+: OR_Q4-Q1 = 3.23, 95% CI = 0.48-21.9, p_trend = 0.26; ER-/PR-: OR_Q4-Q1 = 1.15, 95% CI = 0.63-2.09, p_trend = 0.60. The association was observed for both pre- (OR_Q4-Q1 = 1.35, 95% CI = 1.05-1.73) and post-menopausal (OR_Q4-Q1 = 1.61, 95% CI = 1.03-2.53) breast cancer (p_interaction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.

Keywords: AMH; anti-Müllerian hormone; breast cancer; nested case-control study.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Anti-Mullerian Hormone / blood*
Breast Neoplasms / blood*
Breast Neoplasms / epidemiology*
Case-Control Studies
Female
Humans
Logistic Models
Middle Aged
Odds Ratio
Prospective Studies
Risk Assessment
Risk Factors

Substances

Anti-Mullerian Hormone

Abstract

Publication types

MeSH terms

Substances

Grants and funding