Breast cancer polygenic risk score and contralateral breast cancer risk

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18–1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02–1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547–0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies

Clinicians’ views and experiences with offering and returning results from exome sequencing to parents of infants with hearing loss

Exome sequencing (ES) is an effective method for identifying the genetic cause of hearing loss in infants diagnosed through newborn hearing screening programs. ES has the potential to be integrated into routine clinical care, yet little is known about the experiences of clinicians offering this test to families. To address this gap, clinicians involved in a clinical study using ES to identify the cause of infants’ hearing loss were interviewed to explore their experiences with offering and returning results to parents. Interview transcripts were analysed using inductive content analysis. Twelve clinicians participated: seven genetic counsellors, four clinical geneticists, and one paediatrician. Most clinicians were supportive of offering ES to infants with hearing loss, primarily because results may inform the child’s clinical management. However, some expressed concerns, questioning the utility of this information, particularly for isolated hearing loss. Clinicians had differing views regarding the optimal time to offer ES to families; while some felt that families can manage everything at once, others recommended delaying testing until parents have come to terms with their child’s diagnosis. These findings show the complexity involved in determining how ES should be offered to families following the diagnosis of a child with hearing loss, particularly with regards to when testing is suggested

Clinicians' Views and Experiences with Offering and Returning Results from Exome Sequencing to Parents of Infants with Hearing Loss

Exome sequencing (ES) is an effective method for identifying the genetic cause of hearing loss in infants diagnosed through newborn hearing screening programs. ES has the potential to be integrated into routine clinical care, yet little is known about the experiences of clinicians offering this test to families. To address this gap, clinicians involved in a clinical study using ES to identify the cause of infants' hearing loss were interviewed to explore their experiences with offering and returning results to parents. Interview transcripts were analysed using inductive content analysis. Twelve clinicians participated: seven genetic counsellors, four clinical geneticists, and one paediatrician. Most clinicians were supportive of offering ES to infants with hearing loss, primarily because results may inform the child's clinical management. However, some expressed concerns, questioning the utility of this information, particularly for isolated hearing loss. Clinicians had differing views regarding the optimal time to offer ES to families; while some felt that families can manage everything at once, others recommended delaying testing until parents have come to terms with their child's diagnosis. These findings show the complexity involved in determining how ES should be offered to families following the diagnosis of a child with hearing loss, particularly with regards to when testing is suggested

Clinicians’ views and experiences with offering and returning results from exome sequencing to parents of infants with hearing loss

Exome sequencing (ES) is an effective method for identifying the genetic cause of hearing loss in infants diagnosed through newborn hearing screening programs. ES has the potential to be integrated into routine clinical care, yet little is known about the experiences of clinicians offering this test to families. To address this gap, clinicians involved in a clinical study using ES to identify the cause of infants’ hearing loss were interviewed to explore their experiences with offering and returning results to parents. Interview transcripts were analysed using inductive content analysis. Twelve clinicians participated: seven genetic counsellors, four clinical geneticists, and one paediatrician. Most clinicians were supportive of offering ES to infants with hearing loss, primarily because results may inform the child’s clinical management. However, some expressed concerns, questioning the utility of this information, particularly for isolated hearing loss. Clinicians had differing views regarding the optimal time to offer ES to families; while some felt that families can manage everything at once, others recommended delaying testing until parents have come to terms with their child’s diagnosis. These findings show the complexity involved in determining how ES should be offered to families following the diagnosis of a child with hearing loss, particularly with regards to when testing is suggested