Breast Cancer Research and Treatment

, Volume 148, Issue 1, pp 99–106 | Cite as

A phase II study of medroxyprogesterone acetate in patients with hormone receptor negative metastatic breast cancer: translational breast cancer research consortium trial 007

  • Kathy D. Miller
  • Sandra K. Althouse
  • Lisle Nabell
  • Hope Rugo
  • Lisa Carey
  • Gretchen Kimmick
  • David R. Jones
  • Maria J. Merino
  • Patricia S. Steeg
Clinical trial


Preclinical data suggest that medroxyprogesterone acetate (MPA) has both anti-metastatic and anti-angiogenic activity in the absence of hormone receptors (HR). This phase II trial assessed the activity of MPA alone or in combination with low-dose chemotherapy in patients with metastatic HR-negative breast cancer. Postmenopausal women with HR-negative disease were eligible if they had not received more than 3 chemotherapy regimens for metastatic disease. All patients were treated with MPA 1,000–1,500 mg/day orally; patients in cohort two also received low-dose oral cyclophosphamide and methotrexate (ldCM, 50 mg/day and 2.5 mg twice daily on Days 1 and 2 each week). Tissue and circulating biomarkers were assessed serially. The primary endpoint was clinical benefit response defined as objective response or stable disease >6 months. Thirty patients were enrolled (14 MPA monotherapy; 16 MPA + ldCM); median age was 55 (35–80); nearly all had visceral involvement. Despite dose escalation in 90 % of patients, only 17 (57 %) patients ever achieved MPA trough concentrations >50 ng/ml. One patient developed grade 4 renal failure in the setting of rapid disease progression and dehydration. There were no objective responses. One patient in each cohort (~7 %) had stable disease for > 6 months. Skin Nm23 expression increased after 4 weeks of MPA + ldCM, but there were no significant changes in TSP-1, PAI-1 antigen, or PAI-1 activity. MPA had limited activity and does not warrant further development in patients with HR-negative advanced breast cancer. Poor bioavailability limited exposure despite dose escalation.


Glucocorticoid receptor Metastasis suppressor gene Angiogenesis Thrombospondin-1 Nm023 Plasminogen activator inhibitor type I 



Supported by NIH/NCI P30 CA082709-AV-133 (Avon Partners for Progress Supplement) and the Breast Cancer Research Foundation (KDM). In addition, we are grateful for the funding support to the Translational Breast Cancer Research Consortium (TBCRC) from The AVON Foundation, The Breast Cancer Research Foundation, and Susan G. Komen for the Cure.

Conflict of Interest

None of the authors have any conflicts to disclose


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Kathy D. Miller
    • 1
  • Sandra K. Althouse
    • 1
  • Lisle Nabell
    • 2
  • Hope Rugo
    • 3
  • Lisa Carey
    • 4
  • Gretchen Kimmick
    • 5
  • David R. Jones
    • 1
  • Maria J. Merino
    • 6
  • Patricia S. Steeg
    • 7
  1. 1.Indiana University Melvin and Bren Simon Cancer CenterIndianapolisUSA
  2. 2.University of Alabama BirminghamBirminghamUSA
  3. 3.University of California San FranciscoSan FranciscoUSA
  4. 4.University of North CarolinaChapel HillUSA
  5. 5.Duke University Medical CenterDurhamUSA
  6. 6.Laboratory of PathologyNational Cancer InstituteBethesdaUSA
  7. 7.Women’s Malignancies BranchNational Cancer InstituteBethesdaUSA

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