Review Article | Published:

Tumor dormancy and surgery-driven interruption of dormancy in breast cancer: learning from failures

Nature Clinical Practice Oncology volume 4, pages 699710 (2007) | Download Citation



Primary tumor removal, usually considered intrinsically beneficial, can perturb metastatic homeostasis, and for some patients results in the acceleration of metastatic cancer. The continuous-growth model is required to yield to an interrupted-growth model, the implications of which are episodes of tumor dormancy. This Review analyzes the recent evolution of two paradigms related to the development of breast cancer metastases. The evolution of the paradigms described herein is supported by a growing body of findings from experimental models, and is required to explain breast cancer recurrence dynamics for patients undergoing surgery with or without adjuvant chemotherapy.

Key points

  • Established tumor growth models that assume continuous growth of a tumor fail to explain clinical findings from breast cancer patients with local or distant recurrence; such discrepancies may be explained by tumor dormancy

  • The hazard rate for tumor recurrence soon after surgery displays a pattern that is related to menopausal status: a two-peaked hazard function for premenopausal patients and a single wider peak for postmenopausal patients

  • It has been confirmed that in patients receiving adjuvant chemotherapy, recurrence risk is reduced at the first and third years for both menopausal statuses

  • Subclinical metastases might be induced to grow by the conversion of single noncycling G0 cells or by the switching of avascular micrometastatic foci to active angiogenesis

  • Assuming a triggering effect of surgical removal of the primary tumor, the early sharp recurrence peak seen in premenopausal patients can be ascribed to the switching of micrometastatic foci to the angiogenic phenotype, while the following broader peak might result from interruption of dormancy of a number of single cells

  • For postmenopausal patients, the accelerating effects of surgery are much more modest

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We wish to thank Dr Franca Fossati Bellani, Department of Medical Oncology, National Cancer Institute of Milan, for his long-lasting, friendly and generous contribution, as well as helpful comments and critical appraisal of this manuscript.

Author information


  1. R Demicheli is Senior Medical Researcher, Department of Medical Oncology, National Cancer Institute of Milan, Italy.

    • Romano Demicheli
  2. MW Retsky is Lecturer in Surgery, Department of Vascular Biology, Children's Hospital and Harvard Medical School, Boston, MA, USA.

    • Michael W Retsky
  3. WJM Hrushesky is Senior Clinician Investigator, Research Service, Dorn VA Medical Center, The University of South Carolina, Columbia, SC, USA.

    • William JM Hrushesky
  4. M Baum is Professor Emeritus of Surgery, University College London, London, UK.

    • Michael Baum


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The authors declare no competing financial interests.

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Correspondence to Romano Demicheli.

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