BRCA1 Mutation Testing: Controversies and Challenges (Editorial‪)‬

Breast cancer is a leading cause of significant morbidity and mortality for women. Methods to reliably detect the earliest stages of breast cancer have been widely sought because the success of breast cancer treatment is influenced by how early a malignancy is diagnosed. Current methods for early detection rely on either physical examination to palpate a tumor or radiography. The development of genetic tests that enable accurate risk assessment for individuals in high-risk families has been predicted to have substantial medical benefits. Significant and unprecedented media fanfare informed both medical professionals and the general public about exciting new discoveries in breast cancer genetics, namely, identification of two critically important breast cancer genes BRCA1 and BRCA2, helping to create an immediate demand for clinical tests for these genes. The identification of genetic alterations underlying the development of breast cancer has ushered in an exciting and challenging new era in oncology, genetics, and molecular diagnostics. DNA diagnostic tests for breast cancer genes, including BRCA1, BRCA2, and TP53 (which causes breast cancer in the context of the Li-Fraumeni cancer predisposition syndrome), are currently available in most cases only for individuals who have clear family histories of one of the hereditary breast cancer syndromes. Presymptomatic DNA-based assessment for breast cancer risk has had only limited use in clinical practice to date. In cases of autosomal dominant breast cancer (~5% of all breast cancers), identification of the specific BRCA disease-causing mutation has enabled more-accurate risk-modification counseling for first-degree relatives and facilitated susceptibility testing for family members. Presymptomatic identification of a germ-line BRCA mutation provides individuals with specific, if not yet well studied, options for preventive medical management. For example, initial studies indicate that women who have inherited a mutant BRCA1 allele from an affected mother have a markedly increased risk of developing breast cancer (~85% lifetime risk) or ovarian cancer (~50% lifetime risk) or both [1-5]. These women may choose either increased medical surveillance to detect and treat early tumors or bilateral prophylactic mastectomies and (or) oophorectomies in an attempt to eradicate the tissues that have the greatest potential of becoming malignant. Both choices are associated with some morbidity, and neither choice, unfortunately, absolutely guarantees cancer-free survival.