The incidence of breast cancer among women in North America has nearly doubled in the past 15 years; 1 in 9 women will develop this disease. The current diagnostic procedures (physical examination, laboratory and radiological evaluation), while extremely useful for staging and treatment follow-up, have a very limited value in the early diagnosis of malignant disease. To develop valid diagnostic and prognostic markers, we have cloned cancer-specific genes by the subtractive hybridization technique and are studying the role and expression of these genes at different stages of breast cancer. Mutations of the p53 tumor-suppressor gene are the most common genetic lesion in human cancers and appear to be relatively common (30%) as somatic cell mutations in breast cancer. In the present study, we tested the hypothesis of whether both breast cancer and a history of atypical hyperplastic lesions have an increased frequency of germline p53 mutation, as well as whether these atypical hyperplastic lesions exhibit somatic p53 mutations. The study included patients from 16 families and only two patients showed mutations. In contrast, analysis of the DNA from normal and atypical hyperplastic lesions of the cancer patient samples showed no germline or somatic cell mutations. Our results suggest that the p53 mutations occur during advanced stages in the progression of cancer. Males with breast cancer are far rarer than females. We were interested in finding out whether the mutational spectra of the p53 gene reflects different exposure of hormones to breast tissue in female and male patients. Of 10 male breast tumor samples investigated, only two showed point mutations in corresponding to amino acid residues 248 and 290. One of the point mutations turned out to be a silent change, thus representing only DNA polymorphism. Thus far, unlike cancer in females (30%), male breast cancer (10%) does not appear to be associated with frequent p53 mutations.
