Physiological markers of human breast cancer

Of all diseases that afflict mankind, those described as "cancer" evoke the strongest emotions. "Cancer" connotes pain, protracted suffering, hideous growth, and death. In medically advanced countries, cancer (or more correctly, malignant neoplasms) accounts for a substantial proportion of all deaths. Cancer of the breast is the most frequently occurring malignancy in American women, accounting for 27% of all cancers and ranking as the leading cause of cancer death (National Cancer Institute, 1977). The emotional and social problems associated with breast cancer and its high prevalence has stimulated extensive research efforts. However, in spite of the enormous amounts of time and money invested, the etiology and pathogenesis of cancer remain unclear. The past fifty years have seen great strides in the fields of biochemistry and physiology. It has become apparent that cancer involves changes on the molecular level, most likely alterations in DNA. Cancer mechanisms will be reviewed and their accompanying models analyzed. However, to be able to understand cancer on the molecular level, first you must be able to identify the changes that take place on the physiological level. Such changes would provide markers or indicators of the disease. The prognosis from current breast cancer therapy is often dismal except in those cases where the disease was detected early and the lesion localized. Markers that could be easily identified and are present before clinical manifestation of the disease would facilitate early detection and treatment and serve as the best hope in reducing breast cancer mortality. Individuals identified by these markers could receive more frequent examinations and be watched more closely for the development of breast tumors. Two physiological markers for human breast cancer are proposed. The first is competency of DNA repair. The disease xeroderma pigmentosum (xp) is characterized by a high sensitivity to sunlight and the appearance of an early age of melanomas of the skin. XP individuals were found to be defective in one or more of the mechanisms responsible for DNA repair of uv damage (Setlow et al., 1977) . The possibility that breast cancer results from a similar deficiency is examined and the results reported. Differences in hormone concentrations between high risk breast cancer women and matched controls served as a second physiological marker. The hundred fold increase in breast cancer incidence in women as compared to men and the association of the pituitary-gonadal axis with breast cancer have long implicated hormones as an important risk factor (MacMahon et al., 1973). Statistical analysis of 31 hormonal variables gathered on sixty women over the period of one sexual cycle is performed. Extension of this study to women in Utah pedigrees is propped and the procedures outlined. The value of physiological markers for human breast cancer is obvious in that it can save lives, provide information to better understand the genetics of breast cancer, and give indications of the molecular basis of the disease.