Rachel Hodan

PURPOSE: Germline testing is underutilized and varies by cancer diagnosis. We hypothesized that patient and clinician involvement in cascade testing of relatives varies by the cancer susceptibility (breast v gastrointestinal [GI]) of the affected gene. METHODS: All patients diagnosed with cancer in Georgia or California during 2018-2019 and reported to SEER registries, who were linked to a pathogenic variant (PV) result from testing laboratories, were surveyed 4.5 years postdiagnosis about (1) clinician involvement in result communication to relatives, (2) attitudes about result communication, (3) result communication to relatives, and (4) relatives' testing. PVs were categorized by primary association with breast ( BRCA1, BRCA2, ATM, BARD1, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, STK11, TP53 ) or GI cancers ( MLH1, MSH2, MSH6, PMS2, EPCAM, APC, BMPR1A, CDKN2A, GREM1, POLD1, POLE, SMAD4 ). RESULTS: A total of 4,080 patients were surveyed; 2,183 responded (53.5%). Most had PVs associated with breast (83.4%) versus GI cancers (16.6%). Most (85.0%) reported a genetic counseling visit. Genetic counselors were most involved in encouraging family communication (71.5%, v oncologists 33.4%, surgeons 19.4%), advising how to talk with relatives (55.0%, versus oncologists 18.0%, surgeons 9.1%), and talking directly with relatives (33.4%, v oncologists 12.6%, surgeons 7.0%). Most patients considered sharing results their responsibility (86.8%); they notified 86.8% of first-degree and 44.9% of second-degree relatives. Nearly one third (29.0%) of patients reported that no relative was tested, whereas 18.3% reported that four or more relatives were tested. Outcomes did not differ by affected gene or cancer type ( P > .1). CONCLUSION: Patients with cancer are motivated to communicate PV results to relatives. However, few clinicians are involved and relatives' testing remains low. Novel care delivery models are needed to advance cascade testing and precision risk reduction.

Background: Current guidelines recommend consideration of germline genetic testing for patients with uterine serous carcinoma (USC) but real-world data are limited on completion rates of testing and pathogenic variant (PV) identification. This study aimed to evaluate the rate of genetic testing referral and completion in a cohort of patients with USC, determine the prevalence of clinically meaningful PVs found on testing and explore factors associated with genetics referral and testing completion. Methods: We retrospectively examined the medical records of all individuals diagnosed with USC between 2019 and 2024 seen at a single academic cancer centre. Outcomes of interest included referral for germline genetic testing, completion of testing and testing results. Results: Of 131 individuals included, 5 (3.8%) had prior genetic testing and only 45 (34.4%) were recommended to undergo genetic testing or referred to cancer genetics. Younger individuals and those with a personal history of cancer other than USC or family history of breast or ovarian cancer were more likely to be referred. Nine (26.5%) of 34 individuals who completed germline testing had a PV identified in a cancer-related gene, including BRCA1 , BRCA2 , BRIP1 , CHEK2 , MSH6 , PMS2 and ATM . Only a personal history of cancer other than USC was independently associated with the discovery of a PV on germline genetic testing. In those without a prior personal history of cancer, the PV prevalence was 5.6%. Conclusions: Given the high prevalence of PVs in this population, germline genetic testing for all patients diagnosed with USC can provide clinically meaningful benefit but is currently underused in practice.

PURPOSE: Cascade genetic testing in families with hereditary cancer syndromes is an important strategy to reduce the burden of cancer, but testing of relatives is low. Direct engagement of relatives through cancer survivors is a promising approach to bridge this gap. METHODS: We conducted a population-based cluster-randomized clinical trial (Genetic Information and Family Testing [GIFT]) of an online, direct-to-family, cancer genetic education and communication tool including the offer of home testing to adult relatives of cancer survivors diagnosed in 2018-2019 who carried a pathogenic variant. We selected patients through SEER and surveyed them for eligibility followed by a trial invitation. Two features were randomized: assistance from a human navigator (yes, no) and testing cost (free v $50). We hypothesized that the fraction of relatives tested in a family (primary outcome) would be higher with a navigator and free testing. RESULTS: Four thousand three hundred patients were surveyed and 2,285 responded (53.1%); 2,006 eligible respondents were invited (87.8%) and 414 enrolled (20.6%). Enrolled patients reported a total of 4,946 first- and second-degree relatives (mean, 12.3; standard deviation [SD], 8.6); they invited 948 relatives (19.2%) and 303 enrolled (32.0%). Most enrolled relatives ordered testing (267, 91.3%); more than double were tested in the free versus $50 arm (odds ratio [OR], 2.5 [1.6-3.9]), but the baseline fraction tested was low at 0.03 and thus the absolute increase was modest (0.04 [95% CI, 0.02 to 0.05]). We did not find evidence for increased testing in the navigation arm (OR, 1.3 [0.8-2.1]). CONCLUSION: GIFT is a promising blueprint for online cascade genetic education and testing. Results suggest that a low-cost, population-level intervention could be deployed without a human navigator. Additional intervention strategies are needed to increase the modest invitation and testing uptake observed in this study.

PURPOSE: To examine patient report of engagement with clinicians and relatives about their germline genetic test results across risk groups in women diagnosed with cancer. PATIENTS AND METHODS: We surveyed women age 20-79 years diagnosed with breast, ovarian, or uterine cancer in 2018-19 in Georgia or California, in whom a germline genetic testing yielded a pathogenic variant (PV) in a breast, ovarian, or uterine cancer susceptibility gene (grouped by high v moderate risk) or a variant of unknown significance (VUS) about 4 years after diagnosis (N = 1,767, 52.4% response rate). RESULTS: Most patients with PVs (84.5%) had a genetic counseling visit to discuss test results, and a majority (70.6%) were encouraged to share results with relatives with no difference across PV risk groups. Half of the patients with PV reported that a genetic counselor gave them advice about how to talk to relatives and one third reported that a counselor talked directly with a relative. Physician engagement with patients about family communication of test results was low: one third of patients with high-risk PV reported that their oncologist encouraged them to share results with relatives. Patients with PV shared test results with 80% of first-degree relatives and one third of second-degree relatives. Compared with patients with PVs, those with VUS had less engagement with clinicians about sharing test results with relatives; were less likely to believe that they had a responsibility to share results with family; and were less likely to share results with relatives. CONCLUSION: Patients with PVs share results with many family members but clinician support is insufficient, especially among cancer doctors. A substantial proportion of patients with VUS-only engage relatives about results but more research is needed about the nature of the discussions regarding these indeterminate findings.

PURPOSE: To examine receipt of genetic testing and communication with relatives about results into survivorship after diagnosis of breast cancer. METHODS: Women age 20-79 years diagnosed with early-stage breast cancer in 2014-2015 and reported to the Georgia and Los Angeles County SEER registries were surveyed approximately 7 months and 6 years after diagnosis (n = 1,412). We asked about genetic counseling, testing, and communication with relatives about results. We categorized women into indications for testing on the basis of clinical guidelines at the time of diagnosis and at the time of the follow-up survey (FUPs). RESULTS: A total of 47.4% had indications for genetic testing at any time: 28.0% at baseline and an additional 19.4% at the time of the FUPs (only); 71.9% (95% CI, 67.4 to 76.4) of those with a baseline indication reported genetic testing versus 53.3% (95% CI, 47.3 to 59.2) with an indication at FUPs only and 35.0% (95% CI, 31.6 to 38.4) with no indication ( P < .001). There were no significant racial or ethnic differences in receipt of testing, controlling for age and clinical indications ( P = .239); results for genetic counseling were similar. Only 3.4% of survivors had direct-to-consumer genetic testing (DTCt) for cancer. Testers who reported a pathogenic variant (n = 62) were much more likely to have talked to most or all their first-degree adult relatives about genetic testing than those with a variant of unknown significance (n = 49) or a negative finding (n = 419): 62.7% versus 38.8% and 38.0%, respectively ( P < .001). CONCLUSION: Many women with indications for genetic counseling and testing into survivorship do not receive it. But those tested reach out to family members on the basis of the clinical relevance of their results. Very few patients obtained DTCt, which suggests that these tests do not substitute for clinical testing in breast cancer survivors.

Previous research on family communication of cancer genetic test results has primarily focused on non-Hispanic White patients with high-risk pathogenic variants (PV). There are limited data on patient communication of moderate-risk PVs, variants of uncertain significance (VUS), and negative results. This qualitative study examined communication of positive, negative, and VUS hereditary cancer multi-gene panel (MGP) results in an ethnically and socioeconomically diverse population. As part of a multicenter, prospective cohort study of 2000 patients who underwent MGP testing at three hospitals in California, USA, free-text written survey responses to the question: “Feel free to share any thoughts or experiences with discussing genetic test results with others” were collected from participant questionnaires administered at 3 and 12-months post results disclosure. Content and thematic analyses were performed using a theory-driven analysis, Theory of Planned Behavior (TPB), on 256 responses from 214 respondents. Respondents with high perceived utility of sharing genetic test results often reported positive attitudes towards sharing test results and direct encouragement for genetic testing of others. Respondents with high self-efficacy in the sharing process were likely to report high perceived utility of sharing, whereas patients with low self-efficacy more often had VUS results and were more likely to report uncertainty about sharing. Consistent with TPB, our findings suggest that clinician reinforcement of the utility of genetic testing may increase intent for patients to communicate genetic information. Our findings suggest that clinicians should focus on strategies to improve patient understanding of VUS results.

PURPOSE: New guidelines recommend considering germline genetic testing for all patients with colorectal cancer (CRC). However, there is a lack of data on stakeholders' perspectives on the advantages and barriers of implementing universal germline testing (UGT). This study assessed the perspectives of members of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) regarding the implementation of UGT for patients with CRC, including readiness, logistics, and barriers. METHODS: A cross-sectional survey was sent to 317 active members of CGA-IGC. The survey included sections on demographics, clinical practice specialty, established institutional practices for testing, and questions pertaining to support of and barriers to implementing UGT for patients with CRC. RESULTS: Eighty CGA-IGC members (25%) participated, including 42 genetic counselors (53%) and 14 gastroenterologists (18%). Forty-seven (59%) reported an academic medical center as their primary work setting, and most participants (56%) had more than 10 years of clinical practice. Although most participants (73%) supported UGT, 54% indicated that changes in practice would be required before adopting UGT, and 39% indicated that these changes would be challenging to implement. There was support for both genetics and nongenetics providers to order genetic testing, and a majority (57%) supported a standardized multigene panel rather than a customized gene panel. Key barriers to UGT implementation included limited genetics knowledge among nongenetics providers, time-consuming processes for obtaining consent, ordering tests, disclosing results, and lack of insurance coverage. CONCLUSION: This study demonstrates wide support among hereditary GI cancer experts for implementation of UGT for patients with CRC. However, alternative service delivery models using nongenetics providers should be considered to address the logistical barriers to UGT implementation, particularly the growing demand for genetic testing.

We identified six patients from five families with a recurrent mutation: NM_000059.3 (BRCA2) exon 3 deletion. All families self-identified as Assyrian. Assyrians are an ethnoreligious population of ancient Mesopotamia, now mostly living in modern day Iraq, Syria, Turkey and Iran. They are historically a socially isolated population with intermarriage within their community, living as a religious and language minority in mostly Muslim countries. The probands of each family presented with a classic BRCA2-associated cancer including early-onset breast cancer, epithelial serous ovarian cancer, male breast cancer and/or high-grade prostate cancer, and family history that was also significant for BRCA2-associated cancer. BRCA2 exon 3 deletion is classified as pathogenic and has been previously described in the literature, but it has not been described as a founder mutation in a particular population. We characterise this recurrent BRCA2 pathogenic variant in five Assyrian families in a single centre cohort.

Transgender and gender diverse (TGD) populations with hereditary cancer syndromes face unique obstacles to identifying and obtaining appropriate cancer surveillance and risk-reducing procedures. There is a lack of care provider knowledge about TGD health management. Lynch syndrome (LS) is one of the most common hereditary cancer syndromes, affecting an estimated 1 in 279 individuals. There are no clinical guidelines specific for TGD individuals with LS, highlighting a need to improve the quality of care for this population. There is an urgent need for cancer surveillance recommendations for TGD patients. This commentary provides recommendations for cancer surveillance, risk-reducing strategies, and genetic counseling considerations for TGD patients with LS.