Prevention and therapy for BRCA1/2 mutation carriers and women at high risk for breast and ovarian cancer

• Published in: European journal of cancer prevention Vol. 9; no. 3; pp. 139 - 150
• Main Authors: Kuschel, B, Lux, M P, Goecke, T O, Beckmann, M W
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-06-2000; Lippincott Williams and Wilkins
• Subjects: Adult; Aged; Biological and medical sciences; BRCA2 Protein; Breast Neoplasms - genetics; Breast Neoplasms - prevention & control; Breast Neoplasms - therapy; DNA Mutational Analysis; Female; Female genital diseases; Genes, BRCA1 - genetics; Genetic Predisposition to Disease; Germ-Line Mutation; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Mutation - genetics; Neoplasm Proteins - genetics; Ovarian Neoplasms - genetics; Ovarian Neoplasms - prevention & control; Ovarian Neoplasms - therapy; Primary Prevention - methods; Prognosis; REVIEW; Risk Assessment; Transcription Factors - genetics; Tumors; Human; Chemoprophylaxis; Review; Malignant tumor; Medical screening; Genetic determinism; Female genital diseases; Mammary gland diseases; Ovarian diseases; Ovary; Genetic counseling; Risk factor; Female; Mammary gland
• ISSN: 0959-8278; 1473-5709
• DOI: 10.1097/00008469-200006000-00001

The hereditary breast (BC) and ovarian (OC) cancer syndrome (HBOC) includes genetic alterations of various susceptibility genes such as TP53, ATM, PTEN or MSH2, MLH1, PMS1, PMS2, MSH3 and MSH6, BRCA1 and BRCA2. Germline mutations of the cancer-susceptibility genes BRCA1 and BRCA2 seem to be the major aetiology of the HBOC. Genetic counselling and identification of high-risk families may be essential (1) to provide the best method for genetic testing by explaining the sensitivity and specificity of the methods, (2) to offer the opportunity to participate in specific early cancer detection programmes (breast (self) palpation, ultrasound, mammography and magnetic resonance tomography for breast cancer; vaginal exploration and ultrasound for ovarian cancer), (3) to inform them about prophylactic medication (oral contraceptive pill (OCP), chemoprevention (tamoxifen, raloxifen, aromatase inhibitors)) or surgery (bilateral prophylactic mastectomy or oophorectomy) and (4) to provide individualized psychological support. To fulfil these broad demands, an inter-disciplinary counselling approach (gynaecological oncology, human genetics, molecular biology, psychotherapy) in the setting of a cancer genetic clinic seems the most appropriate. There, participation in predictive genetic testing or the use of preventive or therapeutic options may be discussed extensively with the subjects. In particular, preventive options are emotionally disturbing for the subjects, and in cases of previous cancer. BC chemoprevention for high-risk women does not seem to be as effective as expected. However, OCP reduces the risk for OC. For prophylactic surgery, various points have to be considered, including: (1) individual risk assessment and gain in life expectancy, (2) value of screening and early detection methods or medical prevention, (3) disease characteristics and prognosis, and (4) anxiety and quality of life. Decisions regarding these options have to be individualized and psychological support must be offered during the period of decision and follow-up.