Molecular and cellular lesions associated with breast cancer progression.

Breast cancer may be more than one disease with differing etiologies. At the molecular level, breast cancer may be the result of a complex, dynamic, and stochastic process where there is more than one way to accomplish each of the steps necessary for malignant growth. The well documented biologic heterogeneity of breast cancers may arise from the many possible molecular changes that can accomplish a given step with variable efficiency. Alternatively, this heterogeneity may also reflect various possible orders of acquiring the sum of steps necessary for malignant growth. We have attempted to describe some of the molecular changes associated with breast cancer in the context of this broad conceptual framework. We have found that the capacity for infinite growth in culture usually occurs at a late stage of malignant progression and is frequently associated with activating ras mutations. Loss of heterozygosity at chromosome 11p can occur either early or late in progression, while losses at chromosome loci 1q and 17p, although independent of each other, are found in primary breast cancers. Whether the same molecular and cellular changes are to be found in Japanese patients remains to be determined.