Table 2 Summary of behavioural outcomes

ELSAYEGH ET AL. (2018) [26]

USA

Retrospective cohort study

Individuals diagnosed with breast cancer who underwent multi-gene panel testing between 2014 and 2017 and received either a PV or VUS (n = 314)

• Higher rates of CPM in individuals with a BRCA1/2 and non-BRCA PV compared to those with a VUS (p < 0.0001);

• No significant difference in CPM rates between BRCA1/2 carriers and non-BRCA carriers (p = 0.62)

KURIAN ET AL. (2017) [27]

USA

Cross-sectional study

Females (20–79) diagnosed with stage 0- II breast cancer between 2014 and 2015 who were reported to the undergone genetic testing (n = 666)

• PV were associated with higher rates of bilateral mastectomy compared to those with a negative result (OR 7.7; 95% CI, 3.9 to 15.3)

LUMISH ET AL. (2017) [22]

USA

Cross-sectional study

Patients referred to a cancer genetics clinic due to HBOC risk and underwent genetic testing between June 2013 and May 2015. The study sample (n = 232) was divided into 6 subgroups based upon both their genetic test result (positive, negative, or VUS) and personal cancer history (affected or unaffected)

• Amongst unaffected carriers (n = 14), 92.9% (n = 13) reported their results informed cancer screening and 7.1% (n = 1) informed prophylactic surgery decisions;

• Amongst affected carriers (n = 11), 9.1% (n = 1) reported their results informed cancer screening and 18.2% (n = 2) informed prophylactic surgery decisions

• Amongst unaffected individuals with a VUS (n = 20), 15% (n = 3) reported their results informed prophylactic surgery decisions and 35% (n = 7) reported their results informed cancer screening decisions

• Amongst affected individuals with a VUS (n = 14), 7.1% (n = 1) reported their results informed prophylactic surgery decisions and 21.4% (n = 3) reported their results informed cancer screening decisions

PEDERSON ET AL. (2018) [28]

USA

Retrospective cohort study

Patients diagnosed with triple negative breast cancer (Stage I-IV) between September 2013 and December 2016 and underwent multi-gene panel testing (n = 226)

• Higher rates of CPM in the PV subgroup (88%) compared to the negative (20.1%) and VUS (21.4%) subgroups (p < 0.001). No significant difference noted between VUS and negative subgroups. Note: the PV identified in this sample were limited to BRCA1/2 or PALB2

BUNNELL ET AL. (2017) [29]

USA

Retrospective cohort study

Individuals who underwent multi-gene panel testing to evaluate HBOC risk between July 2013 and May 2014 (n = 136)

• Of the tested individuals, 8.8% (n = 12) received a genetic test result deemed medically actionable. The medical management recommendations changed for 10 (83.3%) of these individuals

MURPHY ET AL. (2017) [30]

USA

Retrospective cohort study

Women recently diagnosed with breast cancer and had genetic testing for hereditary cancer syndromes between January 2013 and August 2015 (n = 138)

• Amongst individuals with a VUS result, 29% (n = 2) had a bilateral mastectomy

IDOS ET AL. (2018) [23]

USA

Prospective longitudinal study

Individuals from three genetics clinics who met clinical guidelines or risk estimate thresholds for genetic testing and underwent multi-gene panel testing (either 25-gene or 28-gene panel) (n = 2000)

• Uptake of prophylactic surgery were reported to be higher in those with a PV (16%) compared to the negative and VUS subgroups (2.3% and 2.4%, respectively; p < 0.001)

CHANG ET AL. (2019) [31]

USA

Retrospective cohort study

Individuals deemed high risk for hereditary breast cancer (based upon NCCN guidelines or insurance criteria) and underwent genetic testing between January 2015 and August 2018 (n = 563)

• Higher rates of prophylactic oophorectomy were reported for individuals with a PV (9.8%) compared to those with a VUS (2.3%) or benign result (2.3%) (p = 0.03)

• Higher rates of prophylactic oophorectomy were reported in individuals with a PV in a high risk gene (10.7%) compared to those in a moderate penetrance gene (1.7%) or genes deemed not-breast cancer specific (2.6%) (p = 0.05)

• No significant differences were noted in reported rates of prophylactic mastectomy

KURIAN ET AL. (2018) [32]

USA

Retrospective cohort study

Females, aged 20–79 diagnosed with stage 0-II breast cancer (between 2013 and 2015) who were reported to have undergone genetic testing (n = 1316)

• The association between BRCA1/2 variants and both surgeons' recommendation to undergo a prophylactic mastectomy and completing a prophylactic mastectomy was stronger than those with a non-BRCA1/2 variant, VUS and negative test result (p < 0.001)

FROST ET AL. (2018) [33]

USA

Retrospective cohort review

Individuals who met NCCN guidelines for genetic evaluation for hereditary cancer between January 2015 and December 2016 (n = 671)

• The genetic test results for 23.3% (n = 156) of the study sample were associated with clinical management recommendations. Of these individuals, 39.7% (n = 62) received breast imaging recommendations; 36.5% (n = 57) individuals received ovarian cancer recommendations (TVUS ± CA125); and 37.2% (n = 58) individuals received prophylactic surgery recommendations

VYSOTSKAIA ET AL. (2020) [34]

USA

Retrospective cohort

Individuals who underwent genetic testing with a hereditary cancer panel (29-genes) between March 2016 and March 2018 were divided into two cohorts: (i) received a pathogenic or likely pathogenic test result (n = 161); (ii) did not receive a pathogenic or likely pathogenic result (control cohort) (n = 149)

• Amongst those with a PV in PALB2, ATM, CHEK2, and/or NBN and were recommended to undergo breast MRI (n = 66): 71% (n = 47) had completed an MRI; 26% (n = 17) reported future intention to have a breast MRI;

• Amongst those with a PV in BRIP1, RAD51C, and/or RAD51D and were recommended to have a RRBSO (n = 9): 89% (n = 8) reported already undergone RRSO; 11% (n = 1) reported future intention to have an RRBSO

CASKEY ET AL. (2020) [35]

USA

Retrospective cohort review

Unaffected women at high risk of developing breast cancer and tested positive for a non-BRCA pathogenic mutation between February 2003 and March 2019 (n = 78)

• The genetic test results led to the following changes in clinical management: 3.8% (n = 3) initiated chemoprevention; 11.5% (n = 9) underwent prophylactic mastectomy; 88.5% (n = 69) initiated active surveillance

BRADBURYET AL. (2020) [24]

USA

Prospective longitudinal study

Individuals > 17 years old with prior BRCA1/2 negative testing and offered multi-gene panel testing between January 2014 and January 2015 (n=249)

• Future intention to undergo mammography declined significantly from baseline to 12 months in the VUS (p < 0.01) and negative result (p=0.04) subgroups.

• Future intention to undergo breast MRI declined significantly from baseline to 12 months in the negative result subgroup (p=0.02).