Factors that differentiate cancer risk management decisions among females with pathogenic/likely pathogenic variants in PALB2, CHEK2, and ATM.

PURPOSE: Following disclosure of pathogenic or likely pathogenic variants in hereditary cancer genes, patients face cancer risk management decisions. Through this mixed-methods study, we investigated cancer risk management decisions among females with pathogenic or likely pathogenic variants in PALB2, CHEK2, and ATM to understand why some patients follow National Comprehensive Cancer Network guidelines, whereas others do not. METHODS: Survey and interview data were cross-analyzed using a 3-stage approach. Identified factors were used to conduct coincidence analysis and differentiate between combinations of factors that result in following or not following guidelines. RESULTS: Of the 13 participants who underwent guideline inconsistent prophylactic surgery, 12 fit 1 of 3 unique patterns: (1) cancer-related anxiety in the absence of trust in care, (2) provider recommending surgery inconsistent with National Comprehensive Cancer Network guidelines, or (3) surgery occurring before genetic testing. Two unique patterns were found among 18 of 20 participants who followed guidelines: (1) anxiety along with trust in care or (2) lack of anxiety and no prophylactic surgery before testing. CONCLUSION: Health care provider recommendations and trust in care may influence whether individuals receive care that is congruent with risk levels conferred by specific genes. Interventions are needed to improve provider knowledge, patient trust in non-surgical care, and patient anxiety.

Sharing genetic test results with family members of BRCA, PALB2, CHEK2, and ATM carriers.

OBJECTIVE: This study explored motivators and challenges/barriers to sharing personal genetic test results (GTR) with family members (FM). METHODS: Semi-structured, in-depth interviews were conducted with 62 women who had a pathogenic or likely pathogenic (P/LP) variant in aBRCA, PALB2, CHEK2, or ATM gene. Selective qualitative data analysis focused on eliciting motivators and challenges/barriers identified by participants when sharing their GTR with FM. RESULTS: Motivators to sharing personal GTR with FM included: health protection and prevention; moral obligation; decisional empowerment; familial ties; written resources; and contextualization for a familial cause for cancer. Challenges/barriers to family sharing included: concern for FM reactions; complexities of information; lack of closeness; perceived relevance; and emotional impact. CONCLUSIONS: All motivators and challenges/barriers were identified across BRCA and non-BRCA carriers, demonstrating commonalities in family sharing of GTR among high- to moderate-penetrance hereditary BC (breast cancer) genes. Despite challenges/barriers, participants disclosed their GTR with most close FM, yet restrictions in communication and/or strain on the timing, manner of disclosing, and strategies used varied across certain FM. PRACTICE IMPLICATIONS: These findings offer healthcare providers and researchers preliminary practical implications for broadly improving family sharing interventions across P/LP variants in BC risk genes by demonstrating important elements to include in family sharing letters.

Breast cancer screening implications of risk modeling among female relatives of ATM and CHEK2 carriers.

BACKGROUND: With the increasing use of multigene panel tests, pathogenic and likely pathogenic (P/LP) variants are identified more frequently in the moderate-penetrance breast cancer genes ATM and CHEK2. Lifetime breast cancer risk among women with P/LP variants in these genes generally exceeds 20%, meeting the threshold at which high-risk breast cancer screening through breast magnetic resonance imaging (MRI) is recommended. METHODS: Among a registry-based sample of 56 ATM and 69 CHEK2 carriers, the authors sought to determine the percentage of relatives in whom a P/LP variant would impact breast cancer surveillance. Lifetime breast cancer risks for unaffected, female first-degree and second-degree relatives were estimated using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA). RESULTS: Among first-degree relatives of ATM and CHEK2 carriers, only 22.6% and 14.9%, respectively, were found to have lifetime breast cancer risks of ≥20% based on family cancer history alone; however, when including the proband's P/LP variant in the model, these percentages increased significantly to 56.6% and 55.3%, respectively (P < .0001 and P < .0001, respectively). Similar increases in lifetime breast cancer risks were found among second-degree relatives. CONCLUSIONS: The results of the current study suggest that the majority of female first-degree and second-degree relatives of ATM and CHEK2 carriers do not qualify for breast MRI based on family cancer history alone. Therefore, testing for these genes, as well as awareness of positive moderate-penetrance breast cancer gene results in the family, may impact MRI eligibility. These findings highlight the potential usefulness of and need for breast cancer risk models that incorporate moderate-penetrance gene positivity to inform screening recommendations among at-risk family members.