The multi‐center morphometric mammary carcinoma project (MMMCP) in the netherlands: Value of morphometrically assessed proliferation and differentiation

The Multi-Center Morphometric Mammary Carcinoma Project (MMMCP) was set up to investigate the reproducibility and prognostic value of routine assessments of morphometric parameters [mean nuclear area (MNA), mitotic activity index (MAI), and multivariate prognostic index (MPI)] and cytometric features (DNA ploidy and index, % S-phase cells, as well as other cell cycle data) in comparison with classical prognostic parameters and steroid receptors. Thirty-four hospitals in six geographic regions participated. In 1988–1989, 3427 patients entered the study and morphometric assessments were made. An interim (1993) survival analysis indicated that MAI, MNA, and MPI are the strongest predictors of outcome. A Phase III randomized prospective multi-center trial [Premenopausal Morphometric Intervention Study (PREMIS)] using these endpoints was initiated in Europe to evaluate adjuvant [cyclophosphamide, methotrexate and 5-fluorouracil (CMF)] chemotherapy versus observation in morphometrically high risk (i.e., MAI > 10), premenopausal, lymph node negative (LN–) breast cancer patients.