Assessing Psychological Morbidity in Cancer-Unaffected BRCA1/2 Pathogenic Variant Carriers: A Systematic Review

Abstract

Female BRCA1/2 pathogenic variant carriers have an increased lifetime risk for breast and ovarian cancer. Cancer-unaffected women who are newly diagnosed with this pathogenic variant may experience psychological distress because of imminent health threat. No comprehensible review on psychological morbidity in cancer-unaffected BRCA1/2 pathogenic variant carriers is currently available. This review aims to give an overview about all available the studies in which psychological outcomes have been assessed in cancer-unaffected BRCA1/2 pathogenic variant carriers, whether as a primary outcome or secondary measurement. A systematic search across four databases (Web of Science, PubMed, ScienceDirect, and EBSCO) was conducted. Studies had to report on cancer-unaffected pathogenic variant carriers (exclusively or separately) and use a validated measure of psychological morbidity to be eligible. Measures were only included if they were used in at least three studies. The final review consisted of 45 studies from 13 countries. Distress measures, including anxiety and cancer worry, were most often assessed. Most studies found a peak of distress immediately after genetic test result disclosure, with a subsequent decline over the following months. Only some studies found elevated distress in carriers compared to non-carriers in longer follow-ups. Depression was frequently investigated but largely not found to be of clinical significance. Quality of life seemed to be largely unaffected by a positive genetic test result, although there was some evidence that younger women, especially, were less satisfied with their role functioning in life. Body image has been infrequently assessed so far, but the evidence suggested that there may be a decrease in body image after genetic test result disclosure that may decrease further for women who opt for a prophylactic mastectomy. Across all the outcomes, various versions of instruments were used, often limiting the comparability among the studies. Hence, future research should consider using frequently used instruments, as outlined by this review. Finally, while many studies included cancer-unaffected carriers, they were often not reported on separately, which made it difficult to draw specific conclusions about this population.

“Identity theft” in BRCA1/2: impact of positive genetic test results and risk-reducing interventions

“…Indeed, data show that cancer-affected, BRCA + individuals have increased psychological distress, anxiety, and depression compared to counterparts without a cancer diagnosis ( Ringwald et al, 2016 ). Yet for BRCA + people without a cancer diagnosis, study results on distress, depression, and quality of life are mixed ( Isselhard et al, 2023 ). Similarly, predictors of emotional and coping responses are divergent and sometimes contradictory.…”

“…Genetic testing for pathogenic variants in breast cancer gene 1/2 ( BRCA1/2 ) can identify individuals at increased cancer risk (specifically breast and ovarian), provide opportunities for risk management (i.e., cancer surveillance) and cancer prevention (i.e., risk-reducing surgery or medication), and benefit blood relatives via cascade carrier screening ( The National Comprehensive Cancer Network, 2023 ). Systematic reviews show that despite many potential physical and psychological benefits (i.e., access to risk management to improve personal and familial health, testing-informed targeted treatment approaches), testing positive for BRCA1/2 may also be associated with psychological distress, anxiety, depression, and diminished quality of life ( Lombardi et al, 2019 ; Butler et al, 2021 ; Isselhard et al, 2023 ). Individuals may also often experience vulnerability, stigma, guilt, and decreased self-confidence ( Mella et al, 2017 ; Hesse-Biber et al, 2022 ).…”