© 2005 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Medroxyprogesterone Acetate and Metastases: Of Mice and (Wo)Men
Correspondence to: V. Craig Jordan, OBE, PhD, DSc, Vice President and Research Director for Medical Sciences, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111 (e-mail: v.craig.jordan{at}fccc.edu).
Chambers raises an interesting argument [based on her recent publications noted in (1)] about treating patients after metastatic spread. In fact, the comments illustrate that the implementation of clinical treatment strategies, translational research, and the conduct of cancer cell biology can each be separate worlds divided by the same language.
No one is disputing the interesting results obtained by Palmieri et al. (2) in vivo. It is important that new ideas be exploited in the search for treatments for estrogen receptor (ER)–negative micrometastatic breast cancer. My criticism was with the use of the words "metastatic colonization," which Palmieri et al. stated to be the end point of the assay in vivo.
Webster's dictionary provides several definitions of the word "colonization." I like "the act of establishing colonies," or perhaps one could select "becoming established in a habitat" or, alternatively, "migration to and settling in." All define colonization as the first stages of spread and survival of a foreign group in a new area. The subsequent stage is micrometastatic growth, which can result in the death of a patient.
An optimal assay for Palmieri et al. (2) to demonstrate inhibition of "metastatic colonization" would be to prevent colony formation completely in the mouse lung by treating the mice with medroxyprogesterone acetate (MPA) at the same time as the breast cancer cells are injected. The cells might not establish colonies, and the resulting strategy of chemoprevention would be an effective application of an increase in the Nm23-HI tumor suppressor gene with MPA. However, the authors did not use this approach, and as a result the assay was not optimal. Cells were injected into mice, and 4 weeks later, after the authors had checked that colonies had formed in the lungs, the mice were treated with MPA. At this point, the act of establishing colonies was complete and the MPA was used to activate a target to stop the growth of the micrometastases.
This idea and the treatment strategy are described as adjuvant therapy by the clinical and translational research communities. Chamber quotes (1) from her recent review the statement that a variety of therapeutic approaches to targeting the micrometastatic growth phase are currently under active development. The clinical breast cancer community has been actively engaged in implementing this strategy for the past 30 years (3), with some success, but it is not referred to as targeting metastatic colonization. It is adjuvant therapy. To their credit, Palmieri et al. (2) plan to test MPA as adjuvant therapy in select ER-negative patients after colonization is complete.
The issues over the timing of treatment demonstrate how the jargon used in the laboratory can be Lost in Translation for the clinical community. Nevertheless, perhaps both communities can agree that the early adjuvant testing of MPA, with its many side effects, should be followed, in the decades ahead, by chemoprevention with a selective glucocorticoid modulator designed to prevent colonization with micrometastases.
REFERENCES
(1) Chambers AF. Re: Medroxyprogesterone acetate and metastases: of mice and (wo)men. J Natl Cancer Inst 2005;97:1225.
(2) Palmieri D, Halverson D, Ouatas T, Horak C, Salerno M, Johnson J, Figg WD, Hollingshead M, Hursting S, Berrigan D, Steinberg SM, Merino MJ, Steeg PS. Medroxyprogesterone acetate elevation of NM23-H1 metastasis suppressor expression in hormone receptor-negative breast cancer. J Natl Cancer Inst 2005;97:632–42.
(3) EBCTCG. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687–717.[CrossRef][Web of Science][Medline]
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J Natl Cancer Inst 2005 97: 1225.
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  V. C. Jordan RESPONSE: Re: Medroxyprogesterone Acetate and Metastases: Of Mice and (Wo)Men J Natl Cancer Inst, August 17, 2005; 97(16): 1225 - 1226. [Full Text] [PDF]
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