The clinical utility and costs of whole-genome sequencing to detect cancer susceptibility variants-a multi-site prospective cohort study.

BACKGROUND: Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer. METHODS: This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken. RESULTS: Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing. CONCLUSIONS: These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability.

Cognitive function, fatigue, and menopausal symptoms in breast cancer patients receiving adjuvant chemotherapy: evaluation with patient interview after formal assessment.

BACKGROUND: Women who receive adjuvant chemotherapy for breast cancer report fatigue, menopausal symptoms and cognitive problems. Here we compare assessment of these symptoms using self-report questionnaires and a researcher-administered screen of cognitive function with the experience of women as revealed in a semi-structured interview. METHODS: Twenty-one women who were receiving adjuvant chemotherapy completed the Functional Assessment of Cancer Treatment-General (FACT-G) self-report questionnaire, and sub-scales for fatigue (FACT-F) and endocrine symptoms (FACT-ES). They were evaluated for cognitive dysfunction using the High Sensitivity Cognitive Screen (HSCS). They then completed a semi-structured interview, which explored the nature and severity of these symptoms and their impact on daily function. RESULTS: All patients experienced fatigue and most had menopausal symptoms. There was reasonable correlation of findings in the interview with FACT-F and FACT-ES scores. The HSCS revealed fewer problems than were reported by patients, and correlated with patient experience only for the domain of memory. Most patients noted adverse changes in other cognitive domains, especially concentration, with substantial effects on every-day function. CONCLUSIONS: Women receiving adjuvant chemotherapy for breast cancer have substantial problems with fatigue, menopausal symptoms and cognitive changes. Formal tests such as the HSCS may fail to adequately capture the perceived impact of symptoms.