1. The antiprogestins have potential as growth-inhibitory compounds against breast cancers. Whether this antitumor activity will be unique among the many other available endocrine therapies for breast cancer remains to be seen. There are at present too few clinical data to assess adequately the clinical potential of antiprogestins in the treatment of metastatic breast cancer, much less to assess their potential applications for adjuvant therapy or chemoprevention.

  2. The exact mechanism by which antiprogestins exert their antitumor effect is unclear at present. However, data suggest that more than one mechanism exists because the receptor-antiprogestin complexes of at least two of the clinically available antiprogestins appear to interact with DNA differently (the mifepristone-receptor complex binds DNA, but the onapristone-receptor complex does not).

  3. Although animal models can provide hypotheses, the biologic complexity and heterogeneity of breast cancer and the limitations of these models will require that many questions be addressed in human clinical trials.

  4. Even if the clinical experience with antiprogestins demonstrates substantial activity with an acceptable toxicity profile, it will still be important to define a unique mechanism or role for the use of antiprogestins as compared to other available endocrine therapies. Further elucidation of the antiproliferative mechanism of action, especially the differentiating effects, and of potential synergistic combination hormonal therapies will be useful in this regard.

Recommendation No. 15. The committee recommends research to clarify the activity of antiprogestins in women with advanced (metastatic) breast cancer. Trials should be conducted by using more homogeneous groups of patients. Potential sources of heterogeneity should be reduced by including patients with only minimal prior therapy for their breast cancer and by performing pharmacokinetic evaluations to ensure consistent drug exposure and to facilitate concentration-response correlations. In these studies, tumor progesterone-receptor and estrogen-receptor status should be measured routinely.

Recommendation No. 16. Clinical trials of antiprogestins for treatment of breast cancer should include ancillary investigations to clarify mechanisms underlying the activity of antiprogestins. Examples of such studies include

  1. histologic evaluation of tumor tissue before and after treatment

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