Background. People often overestimate their risk of developing cancer, which can cause undue worry and unwarranted risk-reducing actions. Standard counseling has a limited and short-lived effect on correcting these misperceptions. We conducted a randomized study to evaluate whether incorporation of visual depictions of risk improves the efficacy and durability of cancer risk counseling. Methods. Sixty-six individuals seen in the Familial Cancer Program were randomized to receive standard counseling or counseling supplemented with 2 interactive visual representations of their 10-year risk of developing the cancer type of greatest concern (enhanced counseling). The primary outcome was accuracy of self-perceived risk (ratio of perceived to objective risk) 2 weeks and 6 months after counseling. Results. Prior to counseling, 80% of participants overestimated their risk. Improvement in self-perception of risk was greater among those individuals randomized to receive enhanced counseling. At the 2-week follow-up, the percentage of participants who continued to overestimate their risk by 5-fold or more was 3 to 4 times lower in those who received enhanced counseling, compared to the standard counseling group. At the 6-month follow-up, sustained improvement in risk perception was most evident among those exposed to visual depictions of their risk. Statistical significance was achieved in chi-square analysis at P \ 0.05, grouping participants' risk estimate as approximately accurate (\2-fold) or different from objective risk to varying degrees. Conclusions. Overestimation of cancer risk among people with a family history of cancer is common. Counseling can improve risk perception, but individuals tend to revert back to their prior misperception 6 months after counseling. By including visual representations of risk during counseling, correction of risk perception was of greater magnitude and more durable.
The RAD51D gene codes a protein-paralog of the RAD51 DNA recombinase, which catalyzes DNA strand exchange during homologous recombination. Similar to BRCA1/BRCA2, mutations in RAD51D both predispose to ovarian carcinoma and impart sensitivity to poly (ADP-ribose) polymerase inhibitors in preclinical studies. Based on cancer risk prediction models, RAD51D mutations pose a moderate-to-high risk for ovarian cancer warranting consideration for risk-reducing surgery. We report a case of serous tubal intraepithelial carcinoma in a patient undergoing risk-reducing total hysterectomy with bilateral salpingo-oophorectomy for a RAD51D pathogenic variant. The histopathologic and p53-immunophenotypic features of this lesion are similar to those reported previously in BRCA1/BRCA2 mutation carriers and those of serous tubal intraepithelial carcinoma associated with sporadic high-grade serous carcinomas. These features include marked increase in nuclear-to-cytoplasmic ratio, loss of cell polarity, absence of ciliation, prominent nucleoli, mitotic activity, epithelial stratification, surface exfoliative changes, and complete loss of p53 staining. Although familial ovarian cancers with mutations in RAD51D-or other genes in the Fanconi anemia pathway-are much less common those with BRCA1/BRCA2 mutations, our findings support a common phenotype for early serous cancers in this pathway.
Objective: We sought to investigate our center's experience with multi-gene panel testing in breast and ovarian cancer patients from a largely rural catchment area. Our goal was to identify predictors of pathogenic variants and assess indicators for expanded genetic testing. Methods: We conducted a retrospective review of breast and ovarian cancer patients who underwent panel testing between May 2011 and April 2016. A variety of commercial gene panels were used with variant classification determined by the individual laboratory. Differences in patient demographics, age of first cancer diagnosis, number of genes tested and tumor characteristics including hormone/HER2 status, histology, differentiation, tumor size and AJCC staging classification were analyzed among pathogenic variant positive, negative, and VUS patient subsets with a chi-square test and one-way ANOVA. Results: We identified 215 patients who underwent panel testing: the average age of patients was 52.9 ± 12 with first cancer onset at 47 ± 12; 27% of patients had undergone prior single-gene testing; 7% of patients had ovarian cancer and 93% of patients had breast cancer. VUS were detected in 18.1% of patients and pathogenic variants were detected in 9.3% of patients. Of the 20 pathogenic variants identified, 1 was detected in BARD1, 2 in BRIP1, 3 in MUTYH, 5 in CHECK2, 2 in BRCA1, 2 in BRCA2, 3 in ATM, 1 in PALB2 and 1 in PMS2. In our breast cancer cohort, there was a statistical difference (p=.03) between patients with VUS, pathogenic variants and negative testing in respect to hormone and HER2 status. Most pathogenic variants (75%) were in patients who were HER2 negative, with the majority of VUS detected in patients who were hormone receptor positive (66%). Between the groups, there were no differences in histology, tumor differentiation, size or AJCC stage classification. However, individuals with pathogenic variants tended to have a younger age of first cancer diagnosis, have higher grade disease and have triple negative tumors. Conclusions: Specific tumor patterns (that is, HER2 negative or triple negative pathology) may be important indicators for genetic testing in breast cancer patients. Expanded panel testing should be considered in patients with a younger age of cancer diagnosis, higher grade disease and triple negative tumors. Citation Format: Hermel DJ, McKinnon WC, Colello L, Greenblatt MS, Wood ME. Expanded panel testing in patients with breast or ovarian cancer in a rural familial cancer program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-17.
10617 Background: Identification of pathogenic germline variants (PGVs) is important in guiding treatment decisions, cancer screening and testing of family members. While genetic testing indications expand, barriers to testing still exist. Streamlined processes for genetic testing are needed. Our study assessed the feasibility of a novel approach in which patients with cancer underwent genetic testing first with genetic counseling after for only those with a PGV. Methods: This was an IRB approved study of patients with metastatic solid tumors within < 1 year of diagnosis. Participants were referred by their oncologist and underwent germline testing with an 84-cancer gene panel after signing informed consent. Results were called to patients by a research coordinator if testing was negative and by a genetic counselor if found to have a variant of uncertain significance. Patients with a pathogenic germline variant (PGV) were called by the genetic counselor and scheduled to meet with the genetics team for full counseling. All patients received a letter documenting results and implications. Patient and provider satisfaction surveys were administered in follow-up. Results: 125 patients were eligible and 91 enrolled. Reasons for lack of participation included: early death or decline in health (n = 11, 32.4%). The mean age of patients was 66 (SD 12.6). 60 (65.9%) were male and 43 (47.3%) resided in a rural area. Cancer types represented included: GI (n = 27, 16.5%), lung (n = 22, 13.4%), prostate (n = 19), and renal (n = 4). A PGV was identified in 13 (14.8%) participants. 10 (76.9%) had follow up with a genetic counselor, 2 (15.4%) declined and 1 (7.7%) died prior to being seen. PGVs identified include: MUTYH (n = 5), MITF (n = 2), CHEK2 (n = 2), WRN (n = 1), RAD51D (n = 1), CDH1 (n = 1), NTHL1 (n = 1). 74 (81.3%) participants completed the survey. The vast majority appreciated having undergone testing (n = 70, 94.6%) and having testing incorporated into an existing appointment (n = 69, 93.2%). 61 (82.4%) participants felt confident in their understanding of the results. All providers (n = 16, 100%) were satisfied with this testing process and most (n = 15, 93.8%) felt that genetic test results were obtained in a timelier fashion and reported interest in continuing this testing process. 5 (38.5%) patients with PGVs had a first degree relative undergo cascade testing within 6 months of results. Conclusions: We show that this paradigm shifting process of testing first and counseling after is feasible and acceptable for cancer patients with high rates of cascade testing. Patients and providers report high satisfaction with this process. This process removes known barriers to testing, such as extra clinic visits and time delays to testing. Further use of this process will require delivering education to patients prior to testing and ensuring that providers are comfortable ordering testing.
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