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.