Cancer genetic risk assessment - Studies on genetic testing, genetic counselling and risk management

Abstract

The assessment for hereditary cancer is a consultative service in clinical genetics and cancer care that includes genetic testing and genetic counselling for patients and their relatives, defining elevated cancer risk, and recommendations for risk management. Study I is a registry study of healthy women with a genetic susceptibility to breast and ovarian cancer due to a BRCA gene variant. We examined the effect of participating in a risk management programme including access to risk-reducing surgery of the breast tissue, ovaries and fallopian tubes. We found expected decreases in cancer incidence and mortality ratio after surgery, but with a remaining increase in mortality ratio compared to the background population, partly due to peritoneal carcinomatosis of ovarian origin. In Study II we investigated a nationwide cohort of 4622 women with suspected hereditary breast and ovarian cancer. An extended genetic screening, from the BRCA genes to 13 now established cancer susceptibility genes, nearly doubled the diagnostic yield. These findings has implications for genetic counselling and clinical guidelines. We describe the genetic yield, correlating it to clinical and tumour characteristics. Study III is an interview study involving at-risk relatives who received a letter about hereditary cancer risk directly from a cancer genetics clinic. The letter is an intervention in an RCT on the effectiveness of the established model of family-mediated risk disclosure to relatives reinforced by a healthcare-mediated letter. Healthcare-mediated risk disclosure through direct letters is perceived by at-risk relatives as a mean to safeguard autonomy and agency, but also as complicated and ethically challenging. Study IV is an interview study with healthcare professionals involved in cancer genetic assessments in cancer genetics units or cancer care mainstream testing. We examined their attitudes regarding patients being counselled about risk disclosure to their relatives. We present the results as four positions that healthcare professionals hold, their focus on the patient or the relative, and their attitudes towards patients’ and healthcare’s responsibilities to relatives.