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BACKGROUND: Lynch syndrome, or hereditary nonpolyposis colorectal cancer, is an autosomal dominant genetic syndrome that predisposes individuals to multiple cancer types. The known cancers associated with Lynch syndrome include colorectal and endometrial cancers as well as cancers of the stomach, ovary, urinary tract, hepatobiliary tract, pancreas, small bowel, and brain. There are no searchable cases of malignant phyllodes of the breast associated with Lynch syndrome. CASE PRESENTATION: Our patient was a 43-year-old Caucasian woman who felt a lump in her left breast and was found to have a spindle cell neoplasm. Definitive surgery revealed a malignant phyllodes tumor. On the basis of her cancer diagnosis and family history of multiple cancers, a Myriad myRisk Hereditary Cancer® test panel of 25 genes was performed. This testing revealed that she had a heterozygous MSH6 mutation as part of the Lynch syndrome panel. Due to positive margins, the patient received adjuvant chemotherapy with doxorubicin and ifosfamide. She also had a subsequent total abdominal hysterectomy and a bilateral salpingo-oophorectomy for risk reduction. She remains in a high-risk surveillance program. Her family members have been tested, which revealed that her two brothers and daughter also carry the genetic mutation. CONCLUSIONS: This case highlights the importance of genetic testing with rare malignancies because the full scope of phenotypic sequelae for known hereditary syndromes has not been mapped.

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The increasing availability of next-generation sequencing for clinical research dramatically improved our understanding of breast cancer genetics and resulted in detection of new mutation variants. Cancer risk data relating to some of these variants are insufficient, prompting the designation of variants of uncertain significance (VUS). The histopathologic characteristics of these variants have not been previously described. We propose to depict these characteristics and determine if invasive carcinomas with similar VUS genes share similar histomorphologic features. In total, 28 invasive breast cancers with VUS were retrospectively identified. Tumor sections were reviewed and a predefined set of histopathologic characteristics were documented and compared. Nine of the 28 cases were variants in the ATM gene and were found to share similar histologic characteristics; all had tumor cells with low nuclear grade, absent tumor infiltrating lymphocytes, as well as a marked desmoplastic response. A subset of the above findings were identified in variants of other genes but none had all findings collectively. Furthermore, variants of ATM gene had smaller tumor size, lower pathologic T stage at presentation, and more favorable surrogate molecular subtype compared to variants of other genes. These findings could potentially be used to reclassify VUS and predict which patients may harbor ATM mutations, and hence could have implications in triaging toward ATM variant identification for potential future targeted therapy.

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BACKGROUND: Dissemination of genetic testing for disease susceptibility, one application of "personalized medicine", holds the potential to empower patients and providers through informed risk reduction and prevention recommendations. Genetic testing has become a standard practice in cancer prevention for high-risk populations. Heightened consumer awareness of "cancer genes" and genes for other diseases (eg, cardiovascular and Alzheimer's disease), as well as the burgeoning availability of increasingly complex genomic tests (ie, multi-gene, whole-exome and -genome sequencing), has escalated interest in and demand for genetic risk assessment and the specialists who provide it. Increasing demand is expected to surpass access to genetic specialists. Thus, there is urgent need to develop effective and efficient models of delivery of genetic information that comparably balance the risks and benefits to the current standard of in-person communication. OBJECTIVE: The aim of this pilot study was to develop and evaluate a theoretically grounded and rigorously developed protocol for telephone communication of BRCA1/2 (breast cancer) test results that might be generalizable to genetic testing for other hereditary cancer and noncancer syndromes. METHODS: Stakeholder data, health communication literature, and our theoretical model grounded in Self-Regulation Theory of Health Behavior were used to develop a telephone communication protocol for the communication of BRCA1/2 genetic test results. Framework analysis of selected audiotapes of disclosure sessions and stakeholders' feedback were utilized to evaluate the efficacy and inform refinements to this protocol. RESULTS: Stakeholder feedback (n=86) and audiotapes (38%, 33/86) of telephone disclosures revealed perceived disadvantages and challenges including environmental factors (eg, non-private environment), patient-related factors (eg, low health literacy), testing-related factors (eg, additional testing needed), and communication factors (eg, no visual cues). Resulting modifications to the communication protocol for BRCA1/2 test results included clarified patient instructions, scheduled appointments, refined visual aids, expanded disclosure checklist items, and enhanced provider training. CONCLUSIONS: Analyses of stakeholders' experiences and audiotapes of telephone disclosure of BRCA1/2 test results informed revisions to communication strategies and a protocol to enhance patient outcomes when utilizing telephone to disclose genetic test results.

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OBJECTIVES: With an increasing demand for genetic services, effective and efficient delivery models for genetic testing are needed. METHODS: In this prospective single-arm communication study, participants received clinical BRCA1/2 results by telephone with a genetic counselor and completed surveys at baseline, after telephone disclosure (TD) and after in-person clinical follow-up. RESULTS: Sixty percent of women agreed to participate; 73% of decliners preferred in-person communication. Anxiety decreased from baseline to post-TD (p=0.03) and satisfaction increased (p<0.01). Knowledge did not change significantly from baseline to post-TD, but was higher post-clinical follow-up (p=0.04). Cancer patients had greater declines in state anxiety and African-American participants reported less increase in satisfaction. 28% of participants did not return for in-person clinical follow-up, particularly those with less formal education, and higher post-disclosure anxiety and depression (p<0.01). CONCLUSIONS: Telephone disclosure of BRCA1/2 test results may not be associated with negative cognitive and affective responses among willing patients, although some subgroups may experience less favorable responses. Some patients do not return for in-person clinical follow-up and longitudinal outcomes are unknown. PRACTICE IMPLICATIONS: Further evaluation of longitudinal outcomes of telephone disclosure and differences among subgroups can inform how to best incorporate telephone communication into delivery of genetic services.

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PURPOSE: Although not currently recommended, genetic testing of minors for adult hereditary cancer syndromes, along with risks and benefits, is still being debated. Thus, we evaluated parent opinions regarding BRCA1/2 testing of minors, in general, and hypothetically, for parents' own minor child. METHODS: Semistructured interviews were conducted to assess parent opinions regarding BRCA1/2 testing in minors, along with parent rationale for and factors associated with these opinions. RESULTS: In total, 246 parents at two academic cancer risk assessment programs who underwent BRCA1/2 testing completed the interview (60% response rate). In response to a dichotomous question, 37% of parents supported testing minors. Responses to an open-ended query suggest that 47% support testing minors in some or all circumstances. Parent negative BRCA1/2 test result (P = .02), parent male sex (P = .03), and minority race (P = .01) were independently associated with support of testing minors. In response to a dichotomous question, 44% of parents reported hypothetical interest in testing their own minor offspring. Responses to an open-ended query suggest that 55% would consider, hypothetically, testing their child in some or all circumstances. Parent negative test result (P = .01), less than a college education (P < .01), and older mean offspring age (P = .05) were associated with interest in testing one's own child. CONCLUSION: Parents' opinions regarding BRCA1/2 testing of minors are divided. Given the lack of evidence supporting either the permission or restriction of BRCA1/2 testing in minors, further evaluation of the risks and benefits of providing genetic risk information and genetic testing to minors for adult-onset disease is needed to inform clinical practice and guidelines.

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