Browsing by Author "Menendez, Carolyn S"

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    ItemOpen Access
    Concordance Between Genomic Alterations Detected by Tumor and Germline Sequencing: Results from a Tertiary Care Academic Center Molecular Tumor Board.
    (The oncologist, 2023-01) Green, Michelle F; Watson, Catherine H; Tait, Sarah; He, Jie; Pavlick, Dean C; Frampton, Garrett; Riedel, Jinny; Plichta, Jennifer K; Armstrong, Andrew J; Previs, Rebecca A; Kauff, Noah; Strickler, John H; Datto, Michael B; Berchuck, Andrew; Menendez, Carolyn S

    Objective

    The majority of tumor sequencing currently performed on cancer patients does not include a matched normal control, and in cases where germline testing is performed, it is usually run independently of tumor testing. The rates of concordance between variants identified via germline and tumor testing in this context are poorly understood. We compared tumor and germline sequencing results in patients with breast, ovarian, pancreatic, and prostate cancer who were found to harbor alterations in genes associated with homologous recombination deficiency (HRD) and increased hereditary cancer risk. We then evaluated the potential for a computational somatic-germline-zygosity (SGZ) modeling algorithm to predict germline status based on tumor-only comprehensive genomic profiling (CGP) results.

    Methods

    A retrospective chart review was performed using an academic cancer center's databases of somatic and germline sequencing tests, and concordance between tumor and germline results was assessed. SGZ modeling from tumor-only CGP was compared to germline results to assess this method's accuracy in determining germline mutation status.

    Results

    A total of 115 patients with 146 total alterations were identified. Concordance rates between somatic and germline alterations ranged from 0% to 85.7% depending on the gene and variant classification. After correcting for differences in variant classification and filtering practices, SGZ modeling was found to have 97.2% sensitivity and 90.3% specificity for the prediction of somatic versus germline origin.

    Conclusions

    Mutations in HRD genes identified by tumor-only sequencing are frequently germline. Providers should be aware that technical differences related to assay design, variant filtering, and variant classification can contribute to discordance between tumor-only and germline sequencing test results. In addition, SGZ modeling had high predictive power to distinguish between mutations of somatic and germline origin without the need for a matched normal control, and could potentially be considered to inform clinical decision-making.
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    Germline Genetic Testing: What the Breast Surgeon Needs to Know.
    (Annals of surgical oncology, 2019-07) Plichta, Jennifer K; Sebastian, Molly L; Smith, Linda A; Menendez, Carolyn S; Johnson, Anita T; Bays, Sussan M; Euhus, David M; Clifford, Edward J; Jalali, Mena; Kurtzman, Scott H; Taylor, Walton A; Hughes, Kevin S
    PURPOSE:The American Society of Breast Surgeons (ASBrS) sought to provide educational guidelines for breast surgeons on how to incorporate genetic information and genomics into their practice. METHODS:A comprehensive nonsystematic review was performed of selected peer-reviewed literature. The Genetics Working Group of the ASBrS convened to develop guideline recommendations. RESULTS:Clinical and educational guidelines were prepared to outline the essential knowledge for breast surgeons to perform germline genetic testing and to incorporate the findings into their practice, which have been approved by the ASBrS Board of Directors. RECOMMENDATIONS:Thousands of women in the USA would potentially benefit from genetic testing for BRCA1, BRCA2, and other breast cancer genes that markedly increase their risk of developing breast cancer. As genetic testing is now becoming more widely available, women should be made aware of these tests and consider testing. Breast surgeons are well positioned to help facilitate this process. The areas where surgeons need to be knowledgeable include: (1) identification of patients for initial breast cancer-related genetic testing, (2) identification of patients who tested negative in the past but now need updated testing, (3) initial cancer genetic testing, (4) retesting of patients who need their genetic testing updated, (5) cancer genetic test interpretation, posttest counseling and management, (6) management of variants of uncertain significance, (7) cascade genetic testing, (8) interpretation of genetic tests other than clinical cancer panels and the counseling and management required, and (9) interpretation of somatic genetic tests and the counseling and management required.
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    The Influence of Age on the Histopathology and Prognosis of Atypical Breast Lesions.
    (The Journal of surgical research, 2019-09) Sergesketter, Amanda R; Thomas, Samantha M; Fayanju, Oluwadamilola M; Menendez, Carolyn S; Rosenberger, Laura H; Greenup, Rachel A; Hyslop, Terry; Parrilla Castellar, Edgardo R; Hwang, E Shelley; Plichta, Jennifer K
    BACKGROUND:Although several prognostic variables and risk factors for breast cancer are age-related, the association between age and risk of cancer with breast atypia is controversial. This study aimed to compare the type of breast atypia and risk of underlying or subsequent breast cancer by age. METHODS:Adult women with breast atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ) at a single institution from 2008 to 2017 were stratified by age at initial diagnosis: <50 y, 50-70 y, and >70 y. Regression modeling was used to estimate the association of age with risk of underlying carcinoma or subsequent cancer diagnosis. RESULTS:A total of 530 patients with atypia were identified: 31.1% < 50 y (n = 165), 58.1% 50-70 y (n = 308), and 10.8% > 70 y (n = 57). The proportion of women with atypical ductal hyperplasia steadily increased with age, compared with atypical lobular proliferations (P = 0.04). Of those with atypia on needle biopsy, the overall rate of underlying carcinoma was 17.5%. After adjustment, older age was associated with a greater risk of underlying carcinoma (odds ratio: 1.028, 95% confidence interval: 1.003-1.053; P = 0.03). Of those confirmed to have atypia on surgical excision, the overall rate of a subsequent cancer diagnosis was 15.7%. Age was not associated with a long-term risk for breast cancer (P = 0.48) or the time to a subsequent diagnosis of carcinoma (log-rank P = 0.41). CONCLUSIONS:Although atypia diagnosed on needle biopsy may be sufficient to warrant surgical excision, older women may be at a greater risk for an underlying carcinoma, albeit the long-term risk for malignancy associated with atypia does not appear to be affected by age.