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Purpose: Tumor-only genomic testing can uncover somatic and germline pathogenic variants [pathogenic/likely pathogenic (P/LP)] in cancer predisposition genes. We describe the prevalence of P/LPs in BRCA1/2 and PALB2 (B1B2P2) across malignancies and the frequency of clinical germline testing (CGT) in patients with P/LPs in B1B2P2 identified on tumor-only testing. Experimental Design: Among 7,575 patients with cancer tested between 2016 and 2018 with the OncoPanel tumor-only sequencing assay, we characterized P/LP frequencies by tumor type, receipt of CGT prior to or within 12 months after OncoPanel, and factors associated with CGT. Results: 272 (3.6%) patients had OncoPanel-detected P/LPs in B1B2P2: 37.5% of P/LPs were in BRCA-related cancers; the remainder were in non-BRCA tumors. P/LPs were detected in ≥5% of breast, pancreatic, prostate, ovarian, nonmelanoma skin, endometrial, small cell lung, and colorectal cancers. 37.9% of patients with P/LPs received CGT prior to OncoPanel; an additional 10.7% underwent CGT within 12 months of OncoPanel. Among 132 with CGT, 88.6% had ≥1 clinical factor for CGT compared with 47.1% who did not undergo CGT. Patients with BRCA tumors were more likely to have CGT compared with those without (81.4% vs. 29.0%, P < 0.0001). Among patients with CGT, 70.5% (93/132) of P/LPs were germline. Conclusions: Tumor-only genomic testing identified P/LPs in B1B2P2 in 3.6% of patients. 52.9% of patients with tumor-detected P/LPs and without CGT did not meet personal or family history criteria for CGT. In addition, some patients with tumor-detected P/LPs were not referred for CGT, especially those with non-BRCA tumors. Given implications for treatment selection and familial cancer risk, processes to reliably trigger CGT from tumor-genomic findings are needed.

Supplementary Table from Identification and Management of Pathogenic Variants in BRCA1, BRCA2, and PALB2 in a Tumor-Only Genomic Testing Program

Supplementary Figure from Identification and Management of Pathogenic Variants in BRCA1, BRCA2, and PALB2 in a Tumor-Only Genomic Testing Program

Purpose:Tumor-only genomic testing can uncover somatic and germline pathogenic variants [pathogenic/likely pathogenic (P/LP)] in cancer predisposition genes. We describe the prevalence of P/LPs in BRCA1/2 and PALB2 (B1B2P2) across malignancies and the frequency of clinical germline testing (CGT) in patients with P/LPs in B1B2P2 identified on tumor-only testing.Experimental Design:Among 7,575 patients with cancer tested between 2016 and 2018 with the OncoPanel tumor-only sequencing assay, we characterized P/LP frequencies by tumor type, receipt of CGT prior to or within 12 months after OncoPanel, and factors associated with CGT.Results:272 (3.6%) patients had OncoPanel-detected P/LPs in B1B2P2: 37.5% of P/LPs were in BRCA-related cancers; the remainder were in non-BRCA tumors. P/LPs were detected in ≥5% of breast, pancreatic, prostate, ovarian, nonmelanoma skin, endometrial, small cell lung, and colorectal cancers. 37.9% of patients with P/LPs received CGT prior to OncoPanel; an additional 10.7% underwent CGT within 12 months of OncoPanel. Among 132 with CGT, 88.6% had ≥1 clinical factor for CGT compared with 47.1% who did not undergo CGT. Patients with BRCA tumors were more likely to have CGT compared with those without (81.4% vs. 29.0%, P < 0.0001). Among patients with CGT, 70.5% (93/132) of P/LPs were germline.Conclusions:Tumor-only genomic testing identified P/LPs in B1B2P2 in 3.6% of patients. 52.9% of patients with tumor-detected P/LPs and without CGT did not meet personal or family history criteria for CGT. In addition, some patients with tumor-detected P/LPs were not referred for CGT, especially those with non-BRCA tumors. Given implications for treatment selection and familial cancer risk, processes to reliably trigger CGT from tumor-genomic findings are needed.

Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in

Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in ATM, CHEK2, PALB2, and other DNA damage repair (DDR) genes beyond BRCA1 or BRCA2. We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.1%) carried a P/LP variant in a DDR gene. Clinical follow-up information was available for 101/156 (64.7%) patients. Genetic test result-based management recommendations were made for 57.8% (n = 59) of patients and for 64.7% (n = 66) of patients’ family members. Most recommendations were made for moderate-to-high risk genes and were consistent with guidelines. Sixty-six percent of patients (n = 39/59) implemented recommendations. This study suggests that P/LP variants in DDR genes beyond BRCA1 and BRCA2 can change clinical management recommendations for patients and their family members, facilitate identification of new at-risk carriers, and impact treatment decisions. Additional efforts are needed to improve the implementation rates of genetic-testing-based management recommendations for patients and their family members.

Transgender individuals are often their own health advocates, especially if seeking hormone therapies and gender-affirmation surgeries. While literature exists in the genetic counseling field that explores the relationship between genetic counselors and lesbian, gay, and bisexual patients, there is less research that directly addresses transgender patients. This study assessed cancer genetic counselors' education, knowledge, and comfort with transgender health issues, such as hormone therapies and gender affirmation surgeries. A survey evaluated comfort with relevant vocabulary terms and performance on written case vignettes to approximate how cancer genetic counselors would facilitate conversations with transgender patients about cancer risks. Conclusions drawn in this study are representative of this subpopulation, which is skewed toward a younger population. Mean similarity between responses and predetermined correct answers on the case vignettes was 78.5%. A majority of participants endorsed wanting more education on implications of transgender identity on cancer risk assessment, a need underscored by some participants reporting their discomfort asking about gender pronouns. There was an overall lack of consensus on breast cancer screening based on estrogen therapy, pedigree symbol use, and testing of a minor prior to hormone therapy. This study adds to the growing literature that highlights the educational needs specific to genetic counseling to promote individualized care for transgender patients.

10528 Background: Tumor-genomic testing is increasingly used to guide treatment decisions in cancer patients. Although tumor-only testing cannot definitively distinguish between germline versus somatic alterations, the identification of pathogenic or likely pathogenic (P/LP) variants in certain genes should prompt consideration of germline testing. Germline P/LPs in BRCA1, BRCA2 and PALB2 ( B1B2PAL) are associated with hereditary cancer syndromes. Methods: We reviewed tumor-only genomic data (Dana-Farber Oncopanel) between 10/2016 and 6/2018 to examine the prevalence of P/LPs in BRCA1, BRCA2, PALB2 among adult cancer patients at Dana-Farber Cancer Institute/Brigham and Women’s Hospital. We characterized the frequency of P/LPs by primary tumor type, confirmation by germline testing before or within 12 months after Oncopanel testing or not, and factors associated with germline testing. Results: Among 7,575 patients, the median age was 62 (range 18-99); 53.9% were female. A total of 272 (3.6%) had P/LPs in BRCA1 (n = 90), BRCA2 (n = 162) and/or PALB2 (n = 29). P/LPs in B1B2PAL were detected in 5.3% (38/712) of breast, 11.9% (34/285) of ovarian, 6.6% (18/272) of pancreatic, and 5.1% (12/234) of prostate cancers. P/LPs in B1B2PAL were also detected in other neoplasms (12.9% (8/62) of non-melanoma skin, 5.0% (43/855) of colorectal, 7.6% (20/264) of endometrial, and 4.6% (10/216) of head and neck cancers). Of 169 patients who had not had prior germline testing, 29/169 (17.2%) completed germline testing within 12 months after Oncopanel; 13 (7.7%) referred for testing declined or did not complete testing within 12 months, 14 (8.3%) died before or within 3 months of the Oncopanel results, and 113 (66.9%) had no documented germline testing within 12 months. Among 132 patients who had germline testing, 117 (88.6%) had a clinical indication based on personal or family history compared to 66/140 (47.1%) who did not undergo germline testing. Among 132/272 (48.5%) germline-tested patients, 70.5% were positive for a germline mutation in B1B2PAL; the remainder had somatic B1B2PAL mutations only. Germline testing was more often performed in patients with B1B2PAL-associated tumors (breast, ovarian, pancreatic and prostate cancers) or other clinical indications for germline testing. Conclusions: A low but clinically meaningful rate of P/LPs in BRCA1, BRCA2 and PALB2 was detected by tumor-only genomic testing in diverse malignancies. Given the implications of B1B2PAL alterations on treatment and familial cancer risk, our data support current NCCN guidelines recommending germline testing among patients with cancer and P/LPs in B1B2PAL detected on tumor-genomic testing and highlights the need for systems to ensure germline testing when indicated.

As genetic testing on somatic tumor tissue becomes a more routine part of personalized cancer treatment, a growing opportunity arises to identify hereditary germline variants within those results. These germline results can affect future cancer screening for both patients and their family members. Finding this germline information can be complicated as a result of differences between somatic and germline testing processes, nomenclature, and outcome goals (e.g., treatment impact). The goal of this review is to highlight differences between somatic and germline testing and outline a potential guide to allow for appropriate clinical interpretation of somatic testing results in order to better facilitate genetic counseling referrals and confirmatory germline testing.

e18705Background: Germline testing guidelines are centered on BRCA1 and BRCA2 despite clear medical management recommendations in several other high and moderate penetrance genes. Clinician utiliza...