Mammographic density: a potential monitoring biomarker for adjuvant and preventative breast cancer endocrine therapies

Michael S. Shawky, Hilary Martin, Honor J. Hugo, Thomas Lloyd, Kara L. Britt, Andrew Redfern and Erika W. Thompson _

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Oncotarget. 2017; 8:5578-5591. https://doi.org/10.18632/oncotarget.13484

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Michael S. Shawky1,2, Hilary Martin3, Honor J. Hugo4,5, Thomas Lloyd6, Kara L. Britt7,8,9, Andrew Redfern3,* and Erik W. Thompson4,5,10,*

1 Department of Head and Neck and Endocrine Surgery, Faculty of Medicine, University of Alexandria, Egypt

2 Department of Surgery, University College Hospital, London, UK

3 School of Medicine and Pharmacology, University of Western Australia, and Department of Medical Oncology, Fiona Stanley Hospital, Perth, Western Australia, Australia

4 Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Australia

5 Translational Research Institute, Brisbane, Australia

6 Department of Radiology, Princess Alexandra Hospital, Brisbane, Australia

7 The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia

8 Peter MacCallum Cancer Centre, Melbourne, Australia

9 Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia

10 Department of Surgery, University of Melbourne, St Vincent’s Hospital, Melbourne, Australia

* These authors have contributed equally to this work

Correspondence to:

Erik W Thompson, email:

Keywords: mammographic density, breast cancer, endocrine therapy, predictive biomarker, surrogate

Received: October 04, 2016 Accepted: October 08, 2016 Published: November 21, 2016


Increased mammographic density (MD) has been shown beyond doubt to be a marker for increased breast cancer risk, though the underpinning pathobiology is yet to be fully elucidated. Estrogenic activity exerts a strong influence over MD, which consequently has been observed to change predictably in response to tamoxifen anti-estrogen therapy, although results for other selective estrogen receptor modulators and aromatase inhibitors are less consistent. In both primary and secondary prevention settings, tamoxifen-associated MD changes correlate with successful modulation of risk or outcome, particularly among pre-menopausal women; an observation that supports the potential use of MD change as a surrogate marker where short-term MD changes reflect longer-term anti-estrogen efficacy. Here we summarize endocrine therapy-induced MD changes and attendant outcomes and discuss both the need for outcome surrogates in such therapy, as well as make a case for MD as such a monitoring marker. We then discuss the process and steps required to validate and introduce MD into practice as a predictor or surrogate for endocrine therapy efficacy in preventive and adjuvant breast cancer treatment settings.

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