H.T. Lynch, C. Snyder, M.J. Casey

An autosomal-dominant inherited trait predisposing women to both breast cancer (BC) and ovarian cancer (OC) was first described in 1971. Subsequent strides were made in identifying mutations in the eventually cloned genes BRCA1 and BRCA2 as being responsible for hereditary BC and OC (HBOC) in many women with early-onset HBOC. More recently, modifiers of BC risk have also been identified and are under study. The biological and molecular genetic pathways for malignant transformation in OC (ovarian epithelium and/or epithelium of the fallopian tube or, possibly, the endometrium and endocervix) remain elusive. The answer to the question 'What have we learned?' which is part of our chapter title unfortunately remains incomplete. However, intensive worldwide research indicates that its malignant transformation is the product of a multi-step process where there is an array of mutations which account for three or more classes of genes, inclusive of proto-oncogenes, tumor suppressor genes and mutator genes. This causal uncertainty heralds an enormous clinical-pathology dilemma, given the fact that epithelial OC, together with related Müllerian duct carcinoma, harbor the highest fatality rates of all gynecologic malignancies.