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Breast cancer treatment and ovarian failure: risk factors and emerging genetic determinants

Nature Reviews Cancer volume 6, pages 886–893 (2006)Cite this article

Abstract

Most premenopausal women diagnosed with primary breast cancer receive adjuvant chemotherapy, and many experience chemotherapy-induced ovarian failure (CIOF). CIOF is associated with menopausal symptoms, fertility concerns and long-term implications including bone loss. Ironically, CIOF might confer a disease-specific benefit to women whose breast cancers express hormone receptors. Risk factors of CIOF include the woman's age at the time of therapy, and the type, dose and schedule of chemotherapy. Because inherited genetic factors have an important role in determining who will experience CIOF, genetic testing has the potential to provide optimal counselling about risks and possible interventions.

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Figure 1: The ovarian–pituitary axis.
Figure 2: Pathway of cytochrome-P450-catalysed cyclophosphamide metabolism.
Figure 3: Associations between genotypes and the development of premature ovarian failure.

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Acknowledgements

D.A.F. is supported by a Pharmacogenetics Research Network grant, and grants from the US National Institutes of Health. D.F.H. is supported by the Fashion Footwear Foundation/QVC Presents Shoes-On-Sale. We wish to thank members of the Pharmacogenetics Network COBRA (Consortium on Breast cancer pharmacogeneomics) team, in particular Z. Desta, T. Skaar and J. Yin for helpful discussions.

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Author notes

  1. Vered Stearns, Bryan Schneider and David A. Flockhart: V.S. and B.S. contributed equally to this work.

Authors and Affiliations

  1. the Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

    Vered Stearns

  2. the Divisions of Hematology/Oncology & Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Bryan Schneider

  3. the Department of Internal Medicine, Breast Oncology Program, University of Michigan Comprehensive Cancer Center, University of Michigan Health and Hospital System, Ann Arbor, Michigan, USA

    Daniel F. Hayes

  4. the Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

    David A. Flockhart

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  1. Vered Stearns
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  2. Bryan Schneider
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  3. N. Lynn Henry
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  4. Daniel F. Hayes
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  5. David A. Flockhart
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Correspondence to Vered Stearns.

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Stearns, V., Schneider, B., Henry, N. et al. Breast cancer treatment and ovarian failure: risk factors and emerging genetic determinants. Nat Rev Cancer 6, 886–893 (2006). https://doi.org/10.1038/nrc1992

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